NZ780876B2 - Fluid pumping and bioreactor system - Google Patents
Fluid pumping and bioreactor system Download PDFInfo
- Publication number
- NZ780876B2 NZ780876B2 NZ780876A NZ78087616A NZ780876B2 NZ 780876 B2 NZ780876 B2 NZ 780876B2 NZ 780876 A NZ780876 A NZ 780876A NZ 78087616 A NZ78087616 A NZ 78087616A NZ 780876 B2 NZ780876 B2 NZ 780876B2
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- cassette
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- pump
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- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/40—Manifolds; Distribution pieces
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/42—Integrated assemblies, e.g. cassettes or cartridges
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/14—Scaffolds; Matrices
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/48—Automatic or computerized control
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
Abstract
Provided herein is a pumping/mixing cassette comprising: a cassette body; a planar structure including at least one wall and a perimeter wall defined upon the cassette body; at least one valve seat surrounded by the at least one wall to define a valve well; cassette sheeting covering the at least one valve seat forming at least one pump chamber; at least one fluid valve; at least one fluid pathway configured to receive fluid from the at least one fluid valve, the fluid moving the cassette sheeting when pressure is exerted on the at least one pump chamber; at least one solution port receiving the fluid from at least one source; at least one reservoir port operably coupled with a fluid reservoir; and a loop out port and at least one loop return port configured to be in communication with ends of a loop line and to allow fluid to flow through the loop line from one portion of the cassette to the at least one loop return port, the at least one loop return port fluidically coupling the cassette with a medium, the cassette including the loop out port fluidically coupling the cassette with at least one reservoir, the cassette including at least one solution port fluidically coupling the cassette with at least one second fluid, the cassette including at least one mix pump in communication with the loop line, the cassette including at least one mix cassette valve managing the routing of the at least one second fluid from the at least one loop out port through the at least one mix pump to the at least one loop return port, the at least one mix pump mixing together a plurality of the at least one second fluid with the fluid from the at least one source.
Description
Provided herein is a pumping/mixing cassette comprising: a cassette body; a planar structure including at least one wall and a perimeter wall defined upon the cassette body; at least one valve seat surrounded by the at least one wall to define a valve well; cassette sheeting covering the at least one valve seat forming at least one pump chamber; at least one fluid valve; at least one fluid pathway configured to receive fluid from the at least one fluid valve, the fluid moving the cassette ng when pressure is exerted on the at least one pump chamber; at least one solution port receiving the fluid from at least one source; at least one reservoir port operably coupled with a fluid reservoir; and a loop out port and at least one loop return port configured to be in ication with ends of a loop line and to allow fluid to flow through the loop line from one portion of the cassette to the at least one loop return port, the at least one loop return port fluidically coupling the cassette with a medium, the cassette including the loop out port fluidically ng the cassette with at least one oir, the cassette including at least one solution port fluidically coupling the cassette with at least one second fluid, the cassette including at least one mix pump in ication with the loop line, the cassette including at least one mix cassette valve managing the routing of the at least one second fluid from the at least one loop out port through the at least one mix pump to the at least one loop return port, the at least one mix pump mixing er a plurality of the at least one second fluid with the fluid from the at least one source. 780876 B2 FLUID PUMPING AND CTOR SYSTEM CROSS REFERENCE TO RELATED APPLICATIONS The present application is a divisional application divided out of NZ 776411, which is itself divided out of NZ 741377 dated 7 October 2016 and claims priority to and the t of U.S. Provisional Application Serial No. 62/246,191 filed October 26, 2015, entitled Fluid Pumping and Bioreactor Set (Attorney Docket No. Q29), U.S. Provisional ation Serial No. 62/239,793 filed October 9, 2015, entitled Tissue Engineering System and Method (Attorney Docket No. Q75), and U.S. Provisional Application Serial No. 62/266,548 filed December 11, 2015, ed Fluid Pumping and Bioreactor System (Attorney Docket No. Q80), each of which is hereby incorporated herein by reference in its entirety. This application is also related to the application NZ 774792 filed on 9 April 2021 (which is also a onal application divided out of NZ 741377 dated 7 October 2016) and to its divisional application NZ 780777 filed on 5 October 2021.
BACKGROUND The present teachings relate to a set of components that enable fluid delivery, and specifically to selectively pumping fluid through a variety of fluid flow pathways to achieve, for example, but not limited to, specimen engineering. ing to the United States Department of Health and Human Services, there were approximately 125,000 individuals in the U.S. alone ng organ transplant as of early July 2015. Wait times vary by organ, but substantial percentages (and in some cases the majority) of individuals must wait for years before a needed organ may become available. As of July 2015, it was ted that about 15% of these individuals should expect to wait for a period of five years or longer. Over this waiting period, among other concerns, individuals may be subjected to reduced y of life, disruptive and demanding medical treatments, and increased mortality rate.
Even after an individual receives a transplant, risks and burdens for the individual still exist. Transplantation may be coupled with the possibility of ion. To help prevent this, medications are ed to suppress the immune system for the rest of the individual’s lifetime. Rejection may still occur an d suppression of the immune system comes with its own suite of concerns.
The sciences of specimen engineering and regenerative medicine present possible solutions which may alleviate such waitlists and problems. One promising technology is the s of decellularization and uent recellularization of a specimen or group of specimens to create compatible specimens for lant. A biological specimen may be a grouping of cells and the ated extra cellular matrix ing, but not limited to a tissue, group of tissues, organ, organ system, or group of organs. With this technology the potential exists, e.g., for an organ which is compatible with a patient’s immune system to be processed on demand into a transplant for the patient.
In general, a specimen or group of specimens such as an organ may be decellularized, ex vivo, with a number of fluids, enzymes, and chemicals. These may include biological grade detergents which can lyse cells. Cellular remains may then be carried away.
Left behind is an extracellular matrix which may serve as a scaffold that may be recellularized with new cells that may be compatible with the target patient. The recellularized extracellular matrix scaffold may be a viable specimen or organ which can then be transplanted into a patient.
The term, ex vivo, is defined herein to refer to activities that occur outside of a body and is inclusive of the term in vitro.
This technology is still, however, maturing and many needs which would allow the benefits of the logy to be realized have yet to be met. Currently, a need exists for a system and process which allow decellularization/recellularization procedures to be performed on a large scale with speed, efficiency, precision, repeatability, versatility, and flexibility.
Additionally, a need exists for a system which is simple to set up and configure and es little to no maintenance/cleaning. These needs may be at least lly met by a potentially able or durable system including a sealable enclosure or container for the target specimen or group of specimens.
SUMMARY The needs set forth herein as well as further needs and advantages are addressed by the present examples, which illustrate solutions and advantages described below. [0008a] In a particular embodiment of the ion, provided herein is apumping/mixing cassette comprising: a cassette body; a planar structure including at least one wall and a perimeter wall defined upon the cassette body; at least one valve seat surrounded by the at least one wall to define a valve well; cassette ng covering the at least one valve seat forming at least one pump chamber; at least one fluid valve; at least one fluid pathway ured to receive fluid from the at least one fluid valve, the fluid moving the te (followed by page 2A) sheeting when pressure is exerted on the at least one pump chamber; at least one solution port receiving the fluid from at least one source; at least one reservoir port operably coupled with a fluid reservoir; and a loop out port and at least one loop return port configured to be in communication with ends of a loop line and to allow fluid to flow h the loop line from one portion of the cassette to the at least one loop return port, the at least one loop return port fluidically coupling the cassette with a medium, the cassette including the loop out port fluidically coupling the te with at least one reservoir, the cassette including at least one solution port fluidically coupling the cassette with at least one second fluid, the cassette including at least one mix pump in communication with the loop line, the cassette including at least one mix cassette valve managing the routing of the at least one second fluid from the at least one loop out port through the at least one mix pump to the at least one loop return port, the at least one mix pump mixing together a plurality of the at least one second fluid with the fluid from the at least one source.
A fluid g system can include, but is not limited to including, a fluid handling set including a cassette having a body and a sheet covering a pumping chamber and a plurality of fluid valves associated with the te, a controller, and a manifold including a plurality of modules. Each of the ity of s can include, but is not limited to including, a pneumatic block including a ity of pressure supply lines and a plurality of module valves. The plurality of module valves can be in communication with the plurality of (followed by page 3) pressure supply lines and a plurality of ?uid outlets. The plurality of pressure supply lines and the plurality of ?uid outlets can be associated with each of the plurality of module valves. At least one of the plurality of ?uid outlets can be in communication with the sheet. Each of the plurality of modules can also include a plurality of module control boards. At least one of the plurality of module control boards can receive a ?rst command from the main controller. At least one of the plurality of module control boards can generate, based on the ?rst command, at least one module command sed to at least one recipient module of the plurality of modules. The at least one recipient module control board can be associated with the at least one recipient module that can receive the at least one module command. The at least one recipient module l board can generate, based on the at least one module command, a plurality of valve commands enabling ?ow to the plurality of ?uid valves of the at least one recipient module. The ity of valve commands can toggle positions of the plurality of ?uid valves.
The plurality of valve commands can selectively apply pressure to the ?exible sheet via the ?uid outlets. id="p-10" id="p-10"
id="p-10"
[0010] The valves can optionally include bi-stable valves. Each of the plurality of modules can optionally be coupled to at least one other module of the plurality of modules.
The pressure supply lines of each of the plurality of modules can ally be in ?uid communication with the pressure supply lines of other of the plurality of modules. The l board of each module can optionally generate ck data on a ermined schedule. id="p-11" id="p-11"
id="p-11"
[0011] A ?uid pumping system for a tissue engineering system can include, but is not d to including, a ?uid handling set including a plurality of tically-controlled umping tes, a main controller, and a manifold including a plurality of pneumatic valve modules. The plurality of pneumatic valve modules can share a plurality of pressure buses. Each of the plurality of pneumatic valve modules can e a plurality of valves. Each of the plurality of valves can have an outlet in pneumatic communication with an associated cassette of the plurality of pneumatically—controlled ?uid-pumping cassettes. Each of the plurality of valves can have at least one inlet in communication with a pressure bus of the plurality of pressure buses. Each of the pneumatic valve modules can include a control board con?gured to command ion of the plurality of valves to selectively supply pressure to the associated cassette. The pressure can pump ?uid through the ?uid handling set. The control board can receive a main controller d from the main controller.
Each of the modules can ally include a portion of each of the plurality of pressures buses. The plurality of pressure buses can be formed when at least one of the plurality pneumatic valve modules is coupled to at least another of the plurality of pneumatic valve modules. The ?uid handling set can optionally include three g cassettes. A ?rst te of the plurality of pneumatically-controlled umping cassettes can optionally include a plurality of source ports, a plurality of outlet ports in communication with at least one storage reservoir, a second cassette of the ity of pneumatically-controlled ?uid-pumping cassettes including a ity of inlet ports in communication with the at least one storage reservoir and a plurality of outlet ports in communication with a bioreactor, and a third cassette of the plurality of pneumatically-controlled umping cassettes including a plurality of inlet ports in communication with the at least one storage reservoir and a plurality of outlet ports in communication with a bioreactor. The ?uid pumping system can optionally include a communications bus enabling communications among the plurality of pneumatic valve modules formed as at least one of the plurality of pneumatic valve modules is coupled to at least r of the plurality of pneumatic valve s.
A ?uid pumping system can include, but is not limited to including, a pneumatically driven ?rst pumping cassette and at least one pneumatically driven second cassette. The ?uid pumping system can also include a storage reservoir, the e reservoir being ted to the ?rst pumping cassette by at least a ?rst ?uid line. The storage reservoir can be connected to the at least one second cassette by at least a second ?uid line. The ?uid pumping system can still further include a bioreactor con?gured to house a ical specimen.
The bioreactor can be in ?uid communication with each of the at least one second cassette. The ?uid pumping system can also include a ld. The manifold can include, but is not limited to including, a plurality of valve modules. The plurality of valve modules can be coupled together to form a plurality of pressure supply buses, a communication bus, and a power bus.
Each of the valve modules can include a plurality of . Each of the valve modules can include a control board. The ?uid pumping system can still further include a main controller con?gured to generate a main controller command directed to the manifold. At least one of the control boards can be con?gured to receive the main controller command. At least one of the control boards can be con?gured to send module commands over the communications bus to recipient modules of the valve modules. The recipient modules can actuate, based on the module commands, the plurality of valves associated with the recipient module. The actuating can effect pumping of ?uid by the ?rst pumping cassette and the at least one second cassette.
The communications bus can optionally include a CANbus. The main controller can optionally be con?gured to generate and send a role d for each of the plurality of valve modules. Each of the role commands can optionally be sent to one of the recipient modules over the communications bus. The role command can ally specify a valve con?guration for each of the plurality of valves of the one of the recipient modules. The control board of the one of the recipient modules can optionally be con?gured to alter a valve setting for each of the plurality of valves associated with the one of the recipient modules based on the role command. The valve setting for each of the recipient module valves can optionally be a default setting. The default setting can optionally be modi?able by the role command.
Each of the control boards can optionally be con?gured to generate valve state data. The control boards can optionally send the valve state data over the communications bus. The valve state data can optionally be generated each time a valve is actuated. Each of the l boards can optionally be red to generate feedback data on a ermined schedule. The l boards can optionally send the feedback data over the communications bus. The predetermined schedule can optionally be periodic, for e, but not limited to, every lOOms. The feedback data can optionally e a pressure data signal generated by a pressure sensor. The pressure sensor can ally be associated with the control board. id="p-15" id="p-15"
id="p-15"
[0015] A system for engineering a tissue can include, but is not limited to including, at least one te having a ?exible sheet covering at least one pumping chamber, the ?exible sheet covering at least one cassette ?uid valve. The system can also include a bioreactor housing the tissue. The bioreactor can be in ?uid communication with the at least one cassette. The system can further include a controller and at least one module. Each at least one module can have at least one pressure bus and at least one valve, where the valve is in ication with the pressure bus. Each at least one module can have an outlet port associated with each or the valves. The outlet port can be in communication with the ?exible sheet. The at least one module can include a ?rst module having a ?rst module processor. The ?rst module processor can receive at least one controller command from the controller and can generate, based on the controller command, at least one second module d addressed to at least one second module. The at least one second module can have a second module processor that can receive the at least one second module command and can generate, based on the at least second module command, at least one valve command. The at least one valve d can govern ?uid ?ow through the at least one valve of the at least one second module. The at least one valve can control pressure applied to the ?exible sheet via the outlet ports. The tissue and the bioreactor can receive the ?uid ?ow metered based on the at least one controller command.
The tissue can be decellularized based on the ?uid ?ow.
A ?uid pumping system for ering a tissue can include, but is not limited to including, a plurality of ?uid pumping cassettes. The ?uid pumping cassettes can be pneumatically lled. The ?uid pumping system can also include a bioreactor housing the tissue. The bioreactor can be in ?uid communication with at least one of the plurality of ?uid pumping cassettes. The ?uid pumping system can still further include a controller and a plurality of pneumatic valve modules sharing a plurality of pressure buses. Each of the plurality of pneumatic valve s can include a plurality of valves. Each of the plurality of valves can have a valve outlet port. The valve outlet port can be in tic communication with at least one of the plurality of ?uid pumping tes. The valve outlet port can be in selective pneumatic communication with at least valve one inlet. The at least one valve inlet can be in communication with at least one of the ity of re buses. Each of the plurality of pneumatic valve modules can include a control board that can receive at least one controller d from the controller. The control board can command, according to the at least one controller command, actuation of the valves of each of the ity of pneumatic valve modules.
The actuation can selectively supply pressure to the associated cassette. The pressure can establish a ?uid pathway Within the associated cassette.
A ?uid pumping system can include, but is not limited to including, a pneumatically driven ?rst cassette and at least one pneumatically driven second cassette. The ?uid pumping system can also e a storage reservoir in ?uid communication with the ?rst cassette and the at least one second cassette and a controller ting at least one command.
The ?uid pumping system can still further include a bioreactor housing a biological specimen.
The bioreactor can be in ?uid communication with the at least one second te. The ?uid pumping system can also include a manifold. The manifold can include, but is not limited to including, a plurality of valve modules. Each of the valve modules can include, but is not d to including, a plurality of valves, a control board, a communication bus enabling data communication among the plurality of valve modules, and a plurality of pressure buses distributing a plurality of pressures to the plurality of valve modules. The at least one valve module of the plurality of valve modules can receive the at least one command. The control board of the at least one valve module can send module commands over the communications bus to at least one ent module of the plurality of valve modules. The plurality of valves of the recipient module can be actuated based on the module commands. The ion can enable pumping of ?uid by the ?rst te and the second cassette. The ?uid can be a tissue engineering agent.
The manifold can optionally include a power bus providing power to the plurality of valve modules. The pumping of the ?uid by the second cassette can ally deliver at least one ularization agent to the biological specimen. The pumping can optionally be in accordance with a predetermined schedule. The pumping of the ?uid can optionally r at least one recellularization agent to the biological specimen. The pumping can optionally be in accordance with the predetermined schedule. id="p-19" id="p-19"
id="p-19"
[0019] A method for engineering a tissue can include, but is not limited to including, covering at least one pumping chamber and at least one ?uid valve of at least one cassette with a ?exible sheet, housing the tissue in a bioreactor, the ctor being in ?uid communication with the at least one cassette, receiving, by at least one module processor, at least one controller command from a controller, generating, by the at least one module processor, at least one module command based on the controller command, the at least one module d being addressed to at least one recipient module, ing, by the at least one recipient module, the at least one module command, and generating, by the at least one ent module, a plurality of valve commands based on the at least one module command. The plurality of valve commands can govern ?uid ?ow through the plurality of valves of the at least one ent module. The at least one valve controlling pressure applied to the ?exible sheet via the outlet ports. The method can further include decellularizing the tissue using the ?uid ?ow d based on the at least one controller command.
A system for mixing solutions for engineering a tissue and providing mixed solutions to the tissue can e, but is not limited to including, a ?uid handling set.
The ?uid handling set can include, but is not limited to including, a plurality of pumping cassettes and at least one storage reservoir. The pumping cassettes can pump the ?uid. The system can also include at least one mixing cassette. The at least one mixing cassette can mix the solutions. The at least one mixing cassette can be in ?uid communication with at least one storage reservoir and can supply the solutions to at least one storage reservoir. The plurality of pumping cassettes can be in communication with the at least one storage reservoir. The system can still further include a bioreactor housing the tissue. The ctor can be in ?uid ication with at least one of the plurality of g tes. The system can also include a controller and a plurality of pneumatic valve modules sharing a ity of pressure buses. Each of the plurality of pneumatic valve modules can include, but is not limited to including, a ity of . Each of the plurality of valves can include, but is not limited to including, an outlet port. The outlet port can be in pneumatic communication with at least one of the at least one mixing cassette and the plurality of pumping cassettes. Each of the plurality of valves can also include at least one inlet that can be in communication with at least one of the plurality of pressure buses. The at least one inlet can be in selective pneumatic communication with the outlet port. Each of the plurality of pneumatic valve modules can include, but is not limited to including, a control board receiving at least one controller command from the controller. The control board can command, according to the at least one controller command, actuation of at least one of the ity of pneumatic valve modules. The actuation can selectively supply pressure to at least one of the at least one mixing cassette and the plurality of pumping cassettes. The pressure can establish a ?uid pathway in the at least one of the at least one mixing cassette and the plurality of pumping cassettes.
The ity of pumping cassettes can optionally include pneumatically controlled cassettes. At least one of the mixing cassette and the plurality of pumping cassettes can optionally be a disposable cassette.
An automated system for mixing ons to engineer a tissue can e, but is not limited to including, a ity of solutions and at least one mixing cassette.
The at least one mixing cassette can mix selected of the ity of solutions. The at least one mixing cassette can be in ?uid communication with the plurality of solutions. The automated system can also include a bioreactor housing the tissue. The bioreactor can be in ?uid communication with at least one of a plurality of bioreactor cassettes. The automated system can still further include a controller and a plurality of pneumatic valve s sharing a plurality of pressure buses. Each of the plurality of pneumatic valve modules can include, but is not limited to including, a plurality of valves. Each of the plurality of valves can include, but is not limited to including, an outlet port. The outlet port can be in pneumatic communication with at least one of the at least one mixing cassette and the plurality of bioreactor cassettes. Each of the plurality of valves can also include at least one inlet being in communication with at least one of the plurality of pressure buses. The at least one inlet can be in selective tic ication with the outlet port. Each of the plurality of tic valve modules can include, but is not limited to including, a control board receiving at least one controller command from the controller. The control board can command, according to the at least one controller command, actuation of the valves of the one of the pneumatic valve modules. The actuation can selectively supply pressure to at least one of the at least one mixing cassette and the plurality of pumping cassettes. The pressure can ish a ?uid pathway in the at least one of the at least one mixing cassette and the plurality of g tes.
An automated system for recellularizing decellularized tissue can include, but is not limited to including, at least one cassette having a e sheet covering at least one pumping chamber. The flexible sheet can cover at least one ?uid valve. The automated system can also include a bioreactor housing the tissue. The bioreactor can be in ?uid communication with the at least one cassette. The automated system can still further e a controller, at least one ?rst module, and at least one second module. Each of the at least one ?rst and second s can include, but is not limited to including, at least one pressure bus and at least one valve. The at least one valve can be in communication with the at least one pressure bus. Each of the at least one ?rst and second modules can include, but is not limited to including, an outlet port associated with each of the at least one valves. The outlet port can be in communication with the ?exible sheeting. The automated system can still further include a processor. The ?rst module can include a ?rst module processor receiving at least one controller command from the controller. The ?rst module processor can generate, based on the controller command, at least one module command addressed to the at least second module. The at least second module can include a second module processor that can receive the at least one second module command and can generate, based on the at least one second module command, a plurality of valve commands.
The plurality of valve commands can govern ?uid ?ow through the at least plurality of valves of the at least one second module. The at least one valve can l pressure applied to the ?exible sheet via the outlet ports. The tissue can receive the ?uid ?ow metered based on the at least one controller d. The tissue can be recellularized based on the ?uid ?ow.
In some con?gurations of the present disclosure, a method for generating a tissue for transplant may include, but is not limited to including, ively decellularizing and recellularizing a supplied tissue. In some con?gurations, the method may e ing the supplied tissue by decellularizing the supplied tissue a plurality of times. In some con?gurations, the method may include re?ning the tissue for transplant by decellularizing the iteratively decellularized and recellularized supplied tissue a plurality of times. In some rations, the method may include introducing at least one agent to the supplied tissue, removing an undesired component of the supplied tissue with the at least one agent, and g the supplied tissue. In some con?gurations, rinsing the supplied tissue may include rinsing the supplied tissue with an isotonic solution. In some con?gurations, rinsing the supplied tissue may include rinsing the supplied tissue with phosphate buffered solution. In some con?gurations, the at least one agent can include, but is not limited to including, a detergent, a Triton series detergent, sodium dodecyl sulfate, peracetic acid, ethanol, an enzyme on, a nuclease, DNase, RNase, protease inhibitors, water, puri?ed water, deionized water, and distilled water.
In some con?gurations, the method may include freezing the supplied tissue. In some con?gurations, the method may include alternately freezing and thawing the ed tissue. In some con?gurations, the method may include introducing endothelial cells, epithelial cells, clara cells, goblet cells, alveolar type I cells, ar type 11 cells to the decellularized supplied tissue.
In some con?gurations, the method may e introducing a cell e to the decellularized supplied tissue. In some con?gurations, the method may include introducing stem cells or cells of at least one tissue c phenotype to the decellularized supplied tissue.
In accordance with another con?guration of the present disclosure, a method for creating a transplantable lung from a donor lung may include, but is not limited to including, decellularizing the donor lung. The method may further include recellularizing the decellularized donor lung. The method may further include decellularizing the recellularized donor lung. The method may further include creating the transplantable lung by recellularizing the decellularized recellularized donor lung. In some con?gurations, the donor lung may include a lung that is from a different species than the ed recipient. In some con?gurations, recellularizing the donor lung may include recellularizing the donor lung with cells from the intended ent.
In accordance with another con?guration of the present disclosure, a method for creating a transplantable tissue from a donor tissue may include, but is not limited to including, ularizing the donor tissue. The method may further include recellularizing the donor tissue. The method may further include repeating decellularization and recellularization of the donor tissue until a prede?ned number of ions have been completed.
In accordance with another con?guration of the present disclosure, a method for iteratively decellularizing and ularizing a donor tissue to generate a transplantable tissue may include decellularizing the donor tissue a ?rst prede?ned number of times. The ?rst prede?ned number of times may be set or predetermined for each iteration of a prede?ned number of ions. The method may r include recellularizing the donor tissue a second prede?ned number of times. The second prede?ned number of times may be set or predetermined for each iteration of the prede?ned number of iterations. The method may further include repeating decellularizati on and recellularization until the prede?ned number of iterations have been completed.
In accordance with another con?guration of the present disclosure, a method for creating a transplantable tissue from a donor tissue may include, but is not limited to including, decellularizing the donor tissue with a ?rst decellularization protocol. The method may further include recellularizing the donor tissue with a ?rst recellularization protocol. The method may further include decellularizing the donor tissue with a second decellularization protocol. The method may r include recellularizing the donor tissue with a second recellularization protocol. In some con?gurations, the method may include decellularizing the donor tissue with a ?rst decellularization ol, recellularizing the donor tissue with a ?rst recellularization protocol, ularizing the donor tissue with a second decellularization protocol, recellularizing the donor tissue with a second recellularization protocol, and ing for a prede?ned number of iterations.
In accordance with another con?guration of the present disclosure, a method for ng a transplantable tissue form a donor tissue may include, but is not limited to including, tively decellularizing the donor tissue until a prede?ned number of decellularization cycles are complete. The method may further include repetitively recellularizing the donor tissue until a prede?ned number of recellularization cycles are complete. The method may r include repeating repetitively decellularizing and repetitively recellularizing until a prede?ned number of method iterations have been completed. In some con?gurations, each cycle of the prede?ned number of ularization cycles may include using a different decellularization protocol. In some con?gurations, each cycle of the prede?ned number of recellularization cycles may include using a different recellularization protocol. In some con?gurations, the donor tissue may include, but is not limited to ing, at least one lung. In some con?gurations the donor tissue may be a lung. In some con?gurations, the donor tissue may include at least a part of a pulmonary circuit. In some con?gurations, the donor tissue may include at least a part of an excretory system. In some con?gurations, the donor tissue may include at least a part of a circulatory system. In some con?gurations, the donor tissue may include a kidney, bladder, ureter, urethrea, heart, ear, liver, trachea, or circulatory vessel.
In accordance with another ration of the present disclosure, a method for creating a lantable tissue from a donor tissue may include, but is not limited to including, decellularizing the donor tissue. The method may further include determining if a prede?ned number of decellularization cycles have been completed and repeating ularizing the donor tissue if the number of decellularization cycles performed is below the prede?ned number of decellularization . The method may further include recellularizing the donor tissue. The method may further e determining if a prede?ned number of recellularization cycles have been completed and repeating recellularizing the donor tissue if the number of recellularization cycles performed is below the prede?ned number of ularization cycles.
In accordance with another ration of the present disclosure, a method for creating a transplantable tissue from a donor tissue may include, but is not limited to including, iteratively decellularizing and ularizing a ed tissue for a number of iterations. Each iteration of the number of iterations may include decellularizing the donor tissue. Each iteration of the number of iterations may include determining if a prede?ned number of decellularization cycles have been completed and ing decellularizing the donor tissue if the number of decellularization cycles performed is below the ned number of decellularization cycles. Each iteration of the number of iterations may include, but is not limited to including, recellularizing the donor tissue. Each iteration of the number of iterations may include, but is not limited to including, determining if a prede?ned number of recellularization cycles have been completed and repeating recellularizing the donor tissue if the number of recellularization cycles performed is below the prede?ned number of decellularization cycles. In some con?gurations, a different decellularization ol may be used in each iteration. In some con?gurations, at least one different decellularization protocol may be used in each ion. In some con?gurations, a different recellularization protocol may be used in each iteration. In some con?gurations, at least one different recellularization protocol may be used in each iteration. In some con?gurations, the decellularization protocol may remain nt in each iteration. In some con?gurations, the ularization ol may remain nt in each iteration. In some con?gurations, the decellularization protocol may remain constant in each iteration while the recellularization protocol differs in at least one iteration. In some con?gurations, the decellularization protocol may remain nt in each iteration while a different recellularization protocol is used in each iteration. In some con?gurations, the ularization protocol may remain constant in each iteration and the decellularization protocol while the decellularization protocol differs in at least one iteration. In some con?gurations, the recellularization protocol may remain constant in each ion while the decellularization protocol differs in each iteration. In some con?gurations, the method may further include ularizing with a ?rst recellularization protocol and a second recellularization ol in alternating fashion. In some con?gurations, the method may further include decellularizing with a ?rst decellularization protocol and a second decellularization protocol in alternating fashion. In some con?gurations, the prede?ned number of decellularization cycles in at least one cycle can be greater than one. In some con?gurations, the prede?ned number of recellularization cycles in at least one cycle can be greater than one.
In some con?gurations, the method may further include ularizing with at least a ?rst decellularization protocol at least once in the number of iterations and a second decellularization protocol at least once in the number of iterations. In some con?gurations, the ?rst decellularization protocol and second decellularization protocol may include using at least one different agent. In some con?gurations, the ?rst decellularization protocol and second decellularization protocol may differ in at least one al parameter. In some con?gurations, the method may further e recellularizing with at least a ?rst recellularization protocol at least once in the number of iterations and a second recellularization protocol at least once in the number of iterations. In some con?gurations, the ?rst recellularization protocol and second recellularization protocol may use at least one different agent. In some con?gurations, the ?rst recellularization protocol and second ularization ol may differ in at least one temporal parameter. In some con?gurations, the method may r include decellularizing with a plurality of different decellularization protocols and recellularizing with a plurality of different recellularization protocols. Each of the plurality of different decellularization protocols and plurality of recellularization ols may be scheduled for use in an iteration of the number of iterations. In some con?gurations, the method may r include decellularizing with a plurality of different decellularization protocols and recellularizing with a plurality of different recellularization protocols. The ularization protocol may be altered at a ?rst rate and the recellularization protocol may be altered at a second rate. In some con?gurations, the ?rst rate can be greater than the second rate. In some con?gurations, the ?rst rate can be less than the second rate.
The system of the present teachings for generating a tissue for transplant can include, but is not limited to including, at least one pump chamber, at least one pressure supplier and power supplier, at least one ?uid supply, at least one ?uid pathway opened and closed by at least one valve, at least one tissue enclosure housing the tissue, and at least one sensor sensing at least the characteristics of the ?uid supplies. The at least one sensor can sense at least pressure and power from the pressure power supplies. The system can r e a user interface receiving ?uid control data, and at least one computer controller. The computer controller can manage the at least one pressure and power supplier to actuate the at least one the pump chamber to pump the at least one ?uid supply into and out of the at least one pump chamber based on a ?rst schedule. The computer controller can also manage the sensor data from the at least one sensor, and manage the ?uid control data. The computer controller can also manage opening and closing the at least one valve to enable or disable ?uid ?ow through the at least one ?uid pathway based on a second schedule, the sensor data, and the ?uid control data.
The computer controller can also manage iteratively alternating decellularization and recellularization of the tissue with the at least one ?uid supply based on the ?rst schedule, the second schedule, the ?uid control data, and the sensor data.
The computer controller can ally manage decellularizing the tissue a ity of consecutive times, and decellularizing the iteratively ularized and recellularized tissue a plurality of times. The computer controller can manage decellularizing by introducing at least one agent to the supplied tissue, removing an undesired component of the supplied tissue with the at least one agent, and rinsing the supplied tissue with at least one rinsing agent. The at least one rinsing agent can optionally be, for example, but not limited to, an isotonic solution and a phosphate buffered solution. The at least one agent can optionally be, but is not limited to being, any of a detergent, a Triton series detergent, sodium dodecyl sulfate, peracetic acid, ethanol detergent, Triton series detergent, sodium dodecyl sulfate, peracetic acid, l, an enzyme solution, a nuclease, DNase, RNase, protease inhibitors, water, puri?ed water, deionized water, and distilled water. The computer controller can optionally manage the decellularizing by managing freezing the supplied tissue and manage the decellularizing by managing alternately freezing and thawing the supplied tissue. The at least one computer controller can optionally manage recellularizing by managing introducing a cell e to the decellularized supplied . The computer controller can optionally manage the recellularizing by managing introducing endothelial cells, epithelial cells, ciliated cells, clara cells, goblet cells, alveolar type 1, and/or alveolar type 11 cells to the decellularized ed tissue. The computer controller can optionally manage the recellularizing by managing introducing stem cells or cells of at least one tissue c phenotype to the decellularized supplied . The second schedule may be dynamically ined based on the ?rst schedule.
In accordance with r con?guration of the present disclosure, a system for engineering a tissue can e, but is not limited to including, at least one cassette having a ?exible sheet covering at least one pumping chamber, the ?exible sheet covering at least one te ?uid valve, a bioreactor housing the tissue, the bioreactor being in ?uid ication with the at least one cassette, a controller generating at least one controller command, and at least one valve module, each of the at least one valve modules, having at least one pressure bus, each of the at least one valve modules having at least one valve operably communicating with the pressure bus, each of the at least one valve modules having an outlet port, the outlet port being associated with each of the at least one valves, the outlet port operably communicating with the e sheet, the at least one valve module including a ?rst module having a ?rst module processor, the ?rst module processor receiving the at least one controller command, the ?rst module sor generating, based on the controller command, at least one second module command sed to at least one second module, the at least one second module having a second module processor receiving the at least one second module command and generating, based on the at least second module command, at least one valve command governing ?uid ?ow through the at least one valve of the at least one second module, the at least one valve controlling pressure applied to the ?exible sheet via the outlet ports, the at least one controller d metering the ?uid ?ow to the tissue and the bioreactor, the tissue being decellularized based on the ?uid ?ow.
In accordance with another con?guration of the present disclosure, an automated system for recellularizing decellularized tissue can include, but is not limited to including, at least one cassette having a ?exible sheet covering at least one g chamber, the ?exible sheet ng at least one ?uid valve, a ctor housing the tissue, the bioreactor being in ?uid communication with the at least one cassette, a controller generating at least one controller command, and at least one ?rst valve module and at least one second valve module, each of the at least one ?rst and second valve modules having at least one re bus and at least one valve, the at least one valve operably communicating with the pressure bus, each of the at least one valves being associated with an outlet port, the outlet port operably communicating with the ?exible sheeting, the ?rst valve module having a ?rst module processor, the ?rst module processor receiving the at least one controller command, the ?rst module processor generating, based on the controller command, at least one module command addressed to the at least second module, the at least second module having a second module sor receiving the at least one second module d and generating, based on the at least one second module command, a plurality of valve commands, the plurality of valve commands governing ?uid ?ow through the at least one valve of the at least one second valve module, the at least one valve controlling re applied to the ?exible sheet via the outlet ports, the at least one controller command metering the ?uid ?ow to the tissue, the tissue being recellularized based on the ?uid id="p-36" id="p-36"
id="p-36"
[0036] In accordance with another con?guration of the present disclosure, a system for engineering a lantable tissue from a donor tissue can include, but is not limited to including, a recipe including recipe steps, a graphical user interface (GUI) receiving GUI input, and a controller ing the recipe steps, the GUI input, and at least one default value, the ller forming directions based on arbitrating the at least one default value, the recipe steps, and the GUI input, the controller executing the directions to engineer the transplantable tissue from the donor tissue. The ller can optionally include updating the GUI and updating the recipe.
In accordance with r con?guration of the present disclosure, a method for decellularizing tissue can include, but is not limited to including, con?guring at least one valve in a ?uid path according to a recipe, continually adjusting the ?uid path by lating the at least one valve based on the recipe, pumping water through the continually- adjusted ?uid path past at least one of the at least one valve to a mix cassette, the amount of the water being based on the recipe, pumping at least one solution through the continually-adjusted ?uid path past at least one of the at least one valve to the mix cassette, the amount of the at least one on being based on the recipe, mixing the water and the at least one solution in the mix cassette to form a medium, the amount of the mixing being based on the recipe, pumping the medium through the continually-adjusted ?uid path to a reservoir based on the recipe, pumping the medium through the continually-adjusted ?uid path from the oir to a bioreactor based on the recipe, the medium becoming a used medium in the ctor, and pumping the used medium through the continually-adjusted ?uid path from the bioreactor to a drain based on the recipe. The water can optionally include deionized water. The method can optionally include ?ltering the water, deaerating the water, and if the amount of the water exceeds a pre—selected threshold, storing at least part of the water. The at least one solution can optionally include concentrated solution. id="p-38" id="p-38"
id="p-38"
[0038] In accordance with another con?guration of the present disclosure, a set for ularizing tissue can include, but is not limited to ing, at least one oir ing a plurality of ports, the plurality of ports including at least one mix port and at least one pump port, at least one bioreactor including at least one bioreactor port, at least one pump cassette, the pump cassette including at least one pump, at least one reservoir port ally ting the at least one pump cassette to the at least one reservoir at the at least one pump port, the at least one pump cassette including at least one bioreactor interface port ?uidically connecting the at least one pump cassette to the at least one bioreactor at the at least one bioreactor port, the at least one pump cassette including at least one ?rst ?uid bus and at least one pump cassette valve, the at least one pump cassette valve managing the routing of a ?rst ?uid from the at least one reservoir through the at least one pump to the at least one bioreactor interface port, at least one mix cassette including at least one dilution port, the at least one dilution port ?uidically coupling the at least one mix cassette with a medium, the at least one mix cassette include at least one oir port ?uidically coupling the at least one mix cassette with the at least one reservoir, the at least one mix cassette including at least one solution port ?uidically coupling the at least one mix cassette with at least one second ?uid, the at least one mix te including at least one mix pump, the at least one mix cassette including at least one second ?uid bus, the at least one mix cassette including at least one mix cassette valve managing the routing of the at least one second ?uid from the at least one solution port through the at least one mix pump to the at least one reservoir port, and tubing enabling the ?uidic connections at least among the at least one ?rst ?uid bus and the at least one second ?uid bus. The at least one reservoir can optionally include at least one vent port, at least one w port, and at least one level sensor. The at least one pump te can optionally include at least one waste port ?uidically coupling the at least one pump cassette to at least one waste receptacle. The at least one pump cassette can optionally include at least one loop line port enabling heating of a ?uid circulating in the at least one pump cassette. The at least one ?rst ?uid bus and the at least one pump cassette valve can optionally manage ?ow from the at least one reservoir through the at least one loop line port. The at least one bioreactor can optionally include an adapter including a ?rst face and an second face opposing the ?rst face, an enclosure including a ?rst section and a second section, the ?rst section including a ?rst side and a second side, the enclosure including a liquid-tight seal between the ?rst section and the ?rst face, the enclosure including at least one enclosure pass-through, the enclosure ing a liquid-tight seal between at least a portion of the second section and at least a portion of the ?rst section, a ?rst ?uid line operably d to the adapter, the ?rst ?uid line ng the at least one enclosure pass-through and the adapter, and a second ?uid line disposed on the second face, the second ?uid line ?uidically coupled with the ?rst ?uid line, the ?rst ?uid line coupled with the second ?uid line forming a closed ?uid path.
In accordance with another ration of the t disclosure, a method for engineering a tissue can include, but is not limited to including, covering at least one pumping chamber and at least one ?uid valve of at least one cassette with a ?exible sheet, housing the tissue in a bioreactor, the bioreactor being in ?uid communication with the at least one cassette, receiving, by at least one module processor, at least one controller command from a controller, generating, by the at least one module processor, at least one module command based on the ller d, the at least one module command being addressed to at least one module, receiving, by the at least one module, the at least one module d, ting, by the at least one module, a plurality of valve commands based on the at least one module command, the plurality of valve commands governing ?uid ?ow h a plurality of valves of the at least one module, the at least one ?uid valve controlling pressure applied to the ?exible sheet via the outlet ports, and decellularizing the tissue using the ?uid ?ow metered based on the at least one controller command. The plurality of pumping cassettes can optionally include pneumatically controlled cassettes. The at least one of mixing cassette and the plurality of pumping cassettes can optionally include disposable cassettes. id="p-40" id="p-40"
id="p-40"
[0040] In accordance with another con?guration of the present disclosure, a method for generating a tissue for transplant can include, but is not limited to including, ively decellularizing and recellularizing a biological en until the tissue is generated.
These aspects of the present teachings are not meant to be exclusive and other features, aspects, and advantages of the present teachings will be readily apparent to those of ordinary skill in the art when read in conjunction with the appended claims and anying drawings.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING id="p-42" id="p-42"
id="p-42"
[0042] These and other features and advantages of the present teachings will be better understood by reading the following ed ption, taken together with the drawings is a schematic block diagram of an example of the ?uid system of the present teachings, id="p-44" id="p-44"
id="p-44"
[0044] is a schematic diagram of a ?uid circuit of another example of the present teachings, is a representational block diagram of an example of an enclosure, a number of ?uid lines, and an adapter of the present teachings, is a representational block diagram of another example of the enclosure of the present teachings having multiple adapter parts, is a representational block diagram of a partially assembled enclosure and a number of ?uid lines of the t teachings; is a entational block diagram of an assembled enclosure and a number of fluid lines of the present teachings; is a perspective diagram of the interior of an example of an enclosure of the present teachings having optional interior tubing connectors; is a perspective diagram of the or of an example of an enclosure of the present teachings having external ?uid lines; is a perspective diagram of the interior of an e of an enclosure of the present teachings having optional tubing connectors; is a side View diagram of the exterior of an example of a sealed enclosure of the present teachings; is a perspective diagram of an example of an enclosure of the t teachings having multiple interior cavities; id="p-54" id="p-54"
id="p-54"
[0054] is a perspective diagram of an example of an enclosure of FIG.
A is a perspective diagram of the interior of an e of an enclosure of the t teachings having optional interior tubing connectors; B is a perspective diagram of a detailed view of the indicated region of A; is a perspective diagram of an example of an enclosure of the present teachings having interior and exterior tubing and an interior adapter; is a perspective diagram of an example of an enclosure of the present teachings having or and exterior tubing and an exterior adapter; id="p-59" id="p-59"
id="p-59"
[0059] A is a perspective diagram of an example of an enclosure of the present teachings having optional interior tubing connectors; B is a ctive diagram of a detailed view of the indicated region of A; is a perspective diagram of an example of an enclosure of the present teachings having pre-cut line inlets; is a perspective diagram of an example of an enclosure of the present teachings having pre-cut line inlets; is a perspective m of an example of the interior of an enclosure of the present teachings having an adapter; is a perspective diagram of an example of an enclosure of the present teachings having an adapter with pre-set line ; is a side view diagram of an example of a sealed enclosure of the present teachings having external barbed ?ttings; is a perspective diagram of an example of a sealed enclosure of the t teachings having exterior barbed ?ttings; is a perspective diagram of an example of an enclosure of the present teachings having interior barbed ?ttings on the adapter; is a perspective diagram of an example of the or of an enclosure of the present teachings; id="p-69" id="p-69"
id="p-69"
[0069] A is a cross sectional view of an example of an enclosure of the present teachings taken at line 14-14 of ; B is a detailed view of region D of A; is a side view diagram of an e of an adapter of the t teachings; id="p-72" id="p-72"
id="p-72"
[0072] is a perspective diagram of an example of an enclosure of the present teachings having barbed s on multiple faces of the adapter; A is a perspective diagram of an example of an adapter of the present teachings having tubing connectors; B is a detailed view of region E of A; id="p-75" id="p-75"
id="p-75"
[0075] is a detailed perspective diagram of an e of an enclosure of the present teachings having interior and exterior ; is a perspective diagram of an example of an enclosure of the present teachings having a ; is a schematic block diagram of components of a system of the present teachings and ?uid and signal pathways of the system; A is a schematic block diagram of components of the l system of the present teachings; B is a schematic block diagram of the ller and items d by the ller of the present teachings; C is a schematic block diagram of the process for managing bolus delivery in the system of the present teachings; D is a graphical user interface of a recipe display of the present teachings; E is a graphical user interface of a priming display of the present teachings; F is a graphical user interface of the components of an operational system of the present teachings; G is a graphical user interface of the components of an operational system as fluid is proceeding h the system; id="p-85" id="p-85"
id="p-85"
[0085] H is a graphical user interface of the components of an operational system as ?uid is proceeding through the system; 1 is a graphical user interface of the components of an operational system as ?uid is proceeding through the system; is a schematic diagram of an example of a fluid handling set of the present teachings; is a representational illustration of an example of an accumulator of the present teachings; is a perspective m of an example of a ?rst cassette of the present teachings having ng exploded away from the cassette; id="p-90" id="p-90"
id="p-90"
[0090] is a schematic diagram of an example of a ?rst side of a first cassette of the present ngs; is a schematic m of an example of a second side of the ?rst cassette of ; FIG‘ 37A is a cross section diagram taken at line 22C-22C of ; id="p-93" id="p-93"
id="p-93"
[0093] B is a cross section diagram taken at line 22D-22D of ; C is an enlarged detailed view of the spacers of FIG‘ 37B; is a perspective view of a ?rst side of the ?rst cassette of ; is a perspective view of a second cassette and te sheeting; FIGs. 40 and 41 are plan views of two sides of one cassette of the present teachings; FIGs. 42 and 43 are plan views of two sides of another cassette of the present teachings; is a perspective pictorial illustration of an example of a ?rst side of a second cassette of the present teachings including cassette sheeting ed away from the second cassette; id="p-100" id="p-100"
id="p-100"
[00100] is a pictorial view a ?rst side of the second cassette of ; is a perspective view of a storage oir of an example of the present teachings; is a medial cross-section view of a storage oir of; FIGs. 46A-46D are flowcharts of methods for iteratively decellularizing and recellularizing a ical specimen; is a perspective diagram of an example of a ?tting of the present teachings; FIGS. 48A-C are perspective diagrams of example ?ttings of the present teachings in various stages of mating with one another; id="p-106" id="p-106"
id="p-106"
[00106] A is a ctive diagram of an example of a ?rst side of ?ttings of the present teachings mated together; B is a perspective diagram of an example of a second side of ?ttings of the present teachings mated er; C is a perspective diagram of an example of a third side of ?ttings of the present teachings mated together; D is a ctive m of an example of a fourth side of ?ttings of the present teachings mated together; ] E a pictorial cross sectional illustration taken at line 261-261 of A of an example of ?ttings of the present teachings mated together; id="p-111" id="p-111"
id="p-111"
[00111] is a perspective diagram illustration of another example of a ?tting of the present teachings; A is a plan view of a ?rst side of another example of ?ttings of the present teachings mated together; B is a plan view of a second side of r example of ?ttings of the present teachings mated together; C is a plan view of a third side of another example of ?ttings of the present teachings mated er; D is a plan view of a fourth side of another example of ?ttings of the present teachings mated together; E is a cross-sectional view of the s ofE at line 27F— 27F; A is a perspective view of another example of a ?tting; B is a plan view of two exemplary ?ttings d for mating; C is a plan view of two exemplary ?ttings which have been mated together; id="p-120" id="p-120"
id="p-120"
[00120] A is a plan view of an e of a second te of the present teachings including a ?tting ly on a loop line; ] B is a perspective view of an example of an enclosure of the present teachings including a ?tting assembly on a line leading to the enclosure. is a perspective diagram of an enclosure of the present teachings having a septum; A is a plan view of a ?tting of the present teachings having a septum; B is a cross sectional view of the ?tting of A; FIG. SSC is a schematic block diagram of a valve module of the present teachings; D is a schematic block diagram of a manifold including the valve modules of the present teachings; ] E-5 51 are a schematic block diagrams of a pneumatic pump/valve systems lled by the manifold assemblies of the present teachings; ] ] is a schematic block diagram of a manifold assembly controlling a variety of electrical and/or electronic components and/or devices; K is a perspective view of a programmable valved manifold module; FIG. SSL is a ctive view of two ted or concatenated programmable valved ld modules; FIG. SSM is a perspective view of a programmable valved manifold module with the controller board disconnected from the valve assemblies and the module base; ] N is a perspective view of a programmable valved manifold module having pneumatic output lines of the module; 0 is a perspective view of manifold assembly having a stack of four banks of grouped or concatenated programmable valved manifold modules; P is a schematic block diagram of a manifold of the present teachings; Q is a ?owchart outlining a procedure which may be used to assign tasks to various s in a ld assembly; id="p-136" id="p-136"
id="p-136"
[00136] R is a schematic diagram of a valve block of the present teachings; FIG. SSS is a schematic block diagram of a regulator of the present teachings; FIG. SST is a perspective view of a pneumatic isolation assembly of the present teachings; id="p-139" id="p-139"
id="p-139"
[00139] is a ?owchart of one example of a method of manufacture of an enclosure of the present teachings; is a rt of e of a method of using an enclosure of the present teachings; is a ?owchart of another example of a method of cture of an enclosure of the present teachings; is a ?owchart of another example of a method of manufacture of an enclosure of the present teachings; is an example ?owchart of a method for assembling a ?uid pumping cassette for tissue engineering; and id="p-144" id="p-144"
id="p-144"
[00144] is an e ?owchart of a method which may be used for manufacturing a tissue engineering set.
DETAILED DESCRIPTION ] Referring now to ?uid circuit 160 can include, but is not limited to including, enclosure 100, which can be, but is not limited to being, a bioreactor in ?uid circuit 160. Enclosure 100 may contain biological specimen 162, which may be, but is not limited to being, a tissue, group of tissues, organ, organ , or group of organs. In some con?gurations, biological specimen 162 may be a lung or pair of lungs. In some con?gurations, a plurality of enclosures 100, for example, but not limited to, connected enclosures 100L () may be included in ?uid t 160 and each may contain biological specimen 162. Fluid circuit 160 can also e any number of ?uid paths 196, 186, 188, 184, 172, 164, 166, 168A, 168B, 185 in various con?gurations. At least some ?uid paths may enter ure 100 in a variety of locations. Fluid may selectively be transferred through such ?uid ys by actuating valves 170A-K of ?uid circuit 160 cooperatively to make and break ?uid communication pathways in ?uid circuit 160. The number and location of valves in various con?gurations may differ from that shown in Still referring to ?uid may be transferred into and out of ure 100 via inlet ?uid path 164, through, for example, but not limited to, supply line 319 () and outlet/drain ?uid path 166 through, for example, but not limited to, drain line 311 () respectively Other ?uid ys, for example, but not limited to, ?uid pathway 185 may also be used for eriing ?uid to and from enclosure 100. In another con?guration, a single ?uid pathway may be used to transfer ?uid both into and out of enclosure 100. Thus, ?uid may be introduced to and removed from enclosure 100 such that biological specimen 162 can be bathed in ?uid. Additionally, ?uid may be recirculated through enclosure 100. Fluid may also be delivered and drawn from or circulated through biological en 162 through one or more specimen ?uid paths 168A, 168B. The quantity, entry , size, etc. of specimen ?uid paths 168A, 168B may depend on biological specimen 162. In various con?gurations, specimen ?uid paths 168A, 168B may be placed in ?uid communication with pre—existing anatomical pathways of biological specimen 162 such that ?uid may be perfused through biological specimen 162.
For example, specimen ?uid paths 168A, 168B may connect to any or a combination of the following: circulatory system pathways (e.g. vasculature, lymphatic vessels), respiratory pathways, ducts (e.g. bile duct), excretory system ?uid pathways, digestive system passageways, anatomical cavities, anatomical canals (e. g. alimentary canal), portions of such canals (e. g. h), or other anatomical pathways. Fluid ?ow through specimen ?uid paths 168A, 168B may be controlled such that the same specimen ?uid path 168A, 168B may be used to both deliver ?uid to or draw ?uid from a biological specimen 162. Thus, with multiple specimen ?uid paths 168A, 168B both antegrade and retrograde perfusion of biological specimen 162 may be performed, in some con?gurations, without recon?guration of the ?uid circuit 160. In some con?gurations ?uid circuit 160 can be recon?gured either tically or manually to control ?uid ?ow.
Continuing to refer to enclosure 100 may be placed in container 174. Container 174 may be ?lled with ?uid such that enclosure 100 can be bathed in and/or suspended in the ?uid. In some con?gurations, ?uid circuit 160 may include container ?uid pathway 172 for transferring ?uid into and out of container 174. atively, enclosure 100 may create a sterile barrier n the interior of enclosure 100 and the nding environment, and container 174 may be ?lled using any ?uid supply, for example, but not limited to, tap water, which may or may not be included in or transferred by ?uid circuit 160. To transfer ?uid through ?uid circuit 160, one or more ?rst and second pumps 176, 178 may be ed. First and second pumps 176, 178 may be any of or a combination of a variety of different pump types. Any le ?uid pump, for example, but not limited to, a peristaltic pump, may be used. In some con?gurations, membrane-based ?uid pumps as described, for example, but not limited to, in relation to US. Patent 5,350,357, ?led March, 3, 1993, and entitled PERITONEAL DIALYSIS SYSTEMS EMPLOYING A LIQUID DISTRIBUTION AND NG CASSETTE THAT EMULATES GRAVITY FLOW, ey Docket Number 1062/147, which is hereby incorporated by reference herein in its entirety, may be used.
Continuing to still further refer to in ?uid circuit 160, second pump 176 and ?rst pump 178 can be included. In some con?gurations, there may be a plurality of second pumps 176 and/or ?rst pumps 178. Second pump 176 may be used to pump ?uid to and from or circulate ?uid through enclosure 100, ical specimen 162, container 174, waste reservoir 180, and/or storage reservoir 182. Fluid in enclosure 100 or ical specimen 162 may be pumped to waste reservoir 180, for example, but not limited to, when the ?uid is spent or to maintain a desired ?uid level within enclosure 100. In ?uid circuit 160, second pump 176 may draw ?uid from enclosure 100 via drain ?uid path 166 or from biological specimen 162 via specimen ?uid paths 168A, 168B. Fluid may then be transferred though waste ?uid path 184 to waste reservoir 180. In some con?gurations, ?uid may ely drain to waste reservoir 180 via drain paths 186 and 188. Second pump 176 may use storage reservoir or reservoirs 182 as a ?uid . First pump 178 may pump ?uid to storage reservoir 182 such that second pump 176 can have a suf?cient supply of ?uid to r to enclosure 100, biological specimen 162, and/or container 174. In some con?gurations, ?rst pump 178 may also be capable of pumping directly to enclosure 100, biological specimen 162, and/or container 174. onally, ?rst pump 178 may supply different varieties of ?uid to storage reservoir or oirs 182 such that second pump 176 may deliver ?uid to enclosure 100 and/or biological en 162 based on a prede?ned recipe or list of steps. First pump 178 may also provide ?uid mixtures to storage reservoir or reservoirs 182. For example, ?rst pump 178 may pump a plurality of different ?uids to create ?uid admixtures and/or dilute one or more solutions to desired concentrations.
One or a number of sources 190 may be included in ?uid circuit 160 and ?rst pump 178 may draw from or deliver to these sources 190 via source ?uid pathway or pathways 196. Sources 190 may be various reservoirs such as, for example, but not limited to, vials, compliant reservoirs, bags, and drums. Sources 190 may contain a variety of ent solutions, mediums, ?uids, ical agents, cells, etc. A non—limiting list of potential contents of sources 190 in Table I is as follows: d Water (Distilled, Medical Grade Water Cell Lysing Agent Reverse Osmosis, DeIonized Detergent (Research Grade, Non-ionic Detergent Ionic Detergent Proteomic Grade, 2D Grade, etc.) rionic Deterent Pol ox eth lene Ether Triton X-100 Deter_ents Sodium Nitro orusside Anti-coa_ulant He arin Sodium Deoxycholate Biocompatible/Osmotically Osmotically Incompatible (SDC) Isotonic Solution Solution (Hypertonic/Hypotonic) Hypertonic salt solution Hank’s Balanced Salt Solution ate Buffered Solution . .NaCl solution Saline Solution Bufferin_ Solutions H Buffers Good’s Buffer HEPES Buffer Catalysts (Chemical or Biolo_ic Enz me Solution Ch mot sin Solution Disase Peesin Collagenase Inhibitors inhibitors Serine protease inhibitors Stre tom cin, etc.
Anti-fun_als Chelatin; A_ents C tocidal A_ents Nucleases Nuclease tors Dyes (e. g. Evan’s Blue Dye) Other Markers (Radioactive Markers, Fluorescent Markers, etc.
Cell Size Particles (eg. 5 Nano Bead Particles (unmarked Heparinized Blood pm nanospheres) or chemically marked eg. for ?uorescence) Hydrolytic Enzyme Hyaluronidase Glucuronidase Neuraminidase Bacterial s (eg. s Alcohols that secrete one or more desired on A,ents l Buffered Formalin Aldeh de Fixation A_ents Alcoholic Fixation Aents Bouin Solution Anti-oxidant Solution Glutathione Eth 1 Ester Cell Culture Media Broths Fisher/Iscove/McCoy/Dulbecco’s Nutrient Solutions etc. Medium l Essential Medium MEM Amino Acid Solution Basal Medium Su.1ements Insulin-Transferrin- Growth Factor Solutions Serums Selenium Serum Xenologous to Fetal Bovine Serum (FB S) Horse Serum Inteneded Reci ient Human Serum Serum From Intended ent Serum with Low pH and/or M_ Ions Heat Inactivated Serum Cell Cultures Cells Non-immunogenic to Intended Reci ient Patient Seci?c Stem Cells Endothelial Cells Epithelial Cells Pluri—potent Cells and/or Induced Pluri- - otent Cells Proenitor Cells Emb onic Stem Cells Adult Stem Cells Whole Blood H drocortisone Differentiation Medium Vitamins Fixed Carbon Source Glucose Aerated Solution or Solution Mitoens An_ioenesis Inducing with High Level of Compounds Dissolved Oxygen TABLE I ] Continuing to refer to contents of sources 190 may be provided in any concentration. Additionally, contents of sources 190 may be provided in various different forms. Contents may be in a liquid form or aqueous on. Alternatively, contents of sources 190 may be in a form which could require reconstitution or rehydration. For example, contents for some sources 190 may be in a dried, powdered, or lyophilized form. If the contents of source 190 require titution, a pump such as ?rst pump 178 in ?uid t 160 may pump a reconstituting agent to source 190 to reconstitute the contents of that source 190. Water source 192 may be, for e, but not limited to, a d water source. Water for water source 192 may be provided via a y of suitable puri?cation means such as a reverse osmosis system or distillation system. In some con?gurations, water source 192 may be supplied by a distillation system such as that described in US. Patent Publication No. 2014/0183025, ?led July 26, 2013, and entitled WATER VAPOR DISTILLATION APPARATUS, METHOD, AND SYSTEM, Attorney Docket Number K95 which is incorporated by reference herein in its entirety. Water from water source 192 may be used for a variety of ations. For example, ?rst pump 178 may be used to draw from water source 192 to reconstitute contents of one or more source 190, or may draw from water source 192 to dilute the contents of source 190. on may occur in source 190, ?rst pump 178 or storage reservoir or reservoirs 182. To provide a desired supply fluid for second pump 176, ?rst pump 178 may pump fluid to storage reservoir or reservoirs 182 from water source 192 and one or more source 190 in speci?ed . In some con?gurations, water source 192 may be replaced with another diluent source or a cell culture source.
Referring now to ?uid circuit 200 can include, but is not limited to including, enclosure 100, ?uid pumps 202, 204, 206, 208, 210, 212, 214, and valves 216A-Z and 218A-218S. By operating ?uid pumps 202, 204, 206, 208, 210, 212, 214 and valves 216A-Z and 218A—2188 cooperatively, ?uid may be pumped throughout ?uid circuit 200. In some con?gurations, ?uid may be drawn into ?uid circuit 200 via pumps 204 and 206. Pumps 204 and 206 may draw ?uid from any of source 190A-F and/or from water source 192. Though six sources 190A-F are shown, any number of sources 190A-F may be in communication with ?uid circuit 200. In some con?gurations, one or more of sources 190A—F may be vented by, for example, vent 197, to the atmosphere. A ?lter 189B between the atmosphere and at least one of the one or more sources 190A—F may be included. In some con?gurations, one or more source 190A-F may be associated with ?lter 189A between the one or more source 190A-F and a valve 216H-216M. Both ?lters 189A and 189B may be included in some con?gurations. Filters 189A, B may be any suitable variety of ?lters in some con?gurations, for example, but not limited to, a 0.2 micron ?lter. In some con?gurations, one or more sources l90A-F may be compliant. Fluid circuit 200 can e partitioned portion 222 which may be disconnected from the rest of ?uid circuit 200 via connectors 224A, 224B. Partitioned portion 222 may be a reusable section or a section which may require infrequent cleaning. Fluid t 200, outside of ioned portion 222, may be disposable and may be replaced after each use, or may be replaced after a de?ned number of uses. Alternatively, ?uid circuit 200, outside of partitioned portion 222, may require cleaning or sterilization after each use or after a prede?ned period of time/number of uses.
Components in ioned portion 222 can include drain reservoir 226 to accommodate waste fluid from ?uid circuit 200. One or more one way valve or check valve 228 can be included to help rage or stop waste ?uid from back ?owing into ?uid circuit 200. Water source 192 for ?uid circuit 200 can be included in partitioned portion 222.
Continuing to refer to a number of components may be included between water source 192 and the rest of ?uid circuit 200. At least one ?lter may be included to isolate non-sterile portions of ?uid circuit 200 from e ns. For example, in some con?gurations, ?rst ?lter 220 can ?lter water entering ?uid t 200 from water source 192.
Filter 220 may help to prevent potential inants in water from water source 192 from entering the rest of ?uid circuit 200, and may help to t backwards contamination. First ?lter 220 may be any le ?lter, and in some con?gurations may be a 0.2 micron ?lter. Inlet valve 218R can be included in partitioned portion 222 sharing a pathway with ?rst ?lter 220.
Valve 218R may be a solenoid valve and may be operated to control the ?ow of water into ?uid circuit 200. Regulator 232 may be included to regulate the pressure of water entering ?uid circuit 200. In some con?gurations, the pressure value which regulator 232 regulates to may be between 5-18 psi (eg. 7 psi), though the pressure value may differ in other con?gurations.
Deaerator 230 may also be included in partitioned portion 222 to remove air from the incoming water. Second ?lter 234 which may be substantially the same as or identical to the ?rst ?lter 220 and may be ed and may provide a redundant aid to protect against any potential contaminants. Second ?lter 234 may also help to prevent backwards contamination. First ?lter 220 and second ?lter 234 may isolate valve 218R and deaerator 230 from the rest of ?uid circuit 200 allowing valve 218R and deaerator 230 to be in a non—sterile portion of ?uid circuit 200..
Depending on pump types, expected ?ow rates, and d throughput, accumulator 236 may be included to help ensure a suf?cient supply of fluid at a desired pressure is available.
Still referring to FIG, 2, pumps 202, 204, and 206 may mix ?uid to create various admixtures or may deliver ?uid directly from a source 190A-F or a water source 192 to storage reservoirs 182A, 182B. Admixtures may include ?uid or solution diluted to a desired concentration and/or various ails" consisting of a variety of ent components. Pumps 202, 204, and 206 may draw ?uid from any source 190A-F and/or water source 192 in a ned ratio and deliver this ?uid to storage oirs 182A, 182B. The prede?ned ratio may be chosen to create the desired ?uid admixture. Storage reservoirs 182A, 182B may e vents 238 which prevent re build up within the storage reservoirs 182A, 182B. In some con?gurations vent ?lter 221 such as a 0.2 micron ?lter may be included in vent 238 between the interior of storage reservoirs 182A, 182B and a vent reservoir, for example, but not limited to, the atmosphere.
Continuing to refer primarily to when storage reservoirs 182A, 182B contain a desired admixture or ?uid, the ?uid may be pumped to/from ure 100 or, for example, biological specimen 162 ( within enclosure 100. In some con?gurations, ?lters 199 may be included. In some con?gurations, ?uid circuit 200 can include pumps 208, 210, 212, and 214 which may be used to control the transfer of ?uid to/from enclosure 100 and to/from biological specimen 162 (. Pumps 208, 210, 212, and 214 may be used to pump ?uid to waste oir 226 when, for example, the ?uid is ered used or spent. Pumps 202, 204, 206, 208, 210, 212, 214 may be any of a variety of pumps. In some con?gurations, pumps 204, 206, 208, 210, 212, 214 may be, but are not limited to being, any of or a combination of the following: centrifugal pumps, positive displacement pumps, peristaltic pumps, diaphragm pumps, vane pumps, and metering pumps. Valves 216A-Z and 218A-218S may be any of or a combination of a variety of valve types including but not limited to the following: solenoid , variable valves, and rotary valves, ball , pinch valves, bi-stable valves and membrane valves. In some con?gurations, each or at least one of valves 216A-Z and 218A-2188 may include a combination of valves which may be of different types. For example, each or at least one of valves 216A-Z and 218A-2188 may include a pneumatic valve which controls a ?uid valve. In some con?gurations, the pneumatic valve may be a bi-stable pressure l valve which supplies pressure to a membrane type "volcano valve" to open/close the no valve". In some rations at least some valves, ?uid pathways, and pumps may be incorporated into a fluid handling cassette or set including a ity of ?uid ng cassettes Referring now primarily to enclosure 100 may be a rigid structure which can be of a substantially constant volume. In other con?gurations, enclosure 100 may be a ?accid structure which may change in volume as ?uid/material is introduced and removed from enclosure 100. In some con?gurations, enclosure 100 may be a bag whose interior volume is sealed from the exterior environment. The seal separating enclosure 100 from the surrounding environment may be a ight and/or liquid tight seal. The seal may allow the interior of enclosure 100 to remain sterile while the or of enclosure 100 is in a non-sterile environment. Enclosure 100 may include adapter 23. Adapter 23 may serve as a tubing interface which can include a variety of enclosure pass-throughs 1002 which can extend from ?rst side 23A of adapter 23 to opposing second side 23B of adapter 23. Pass-throughs 1002 may be s such as ori?ces 28 (. First side 23A of adapter 23 may face or be associated with the exterior of enclosure 100 while second side 23B of adapter 23 may face the or of enclosure 100. Pass-throughs 1002 in adapter 23 may provide ports for a number of ?uid lines or tubes 1000A, 1000B, 1000C, 1000D. Fluid lines 1000A, 1000B, 1000C, 1000D may be fed through or penetrate through pass-throughs 1002 from either of ?rst side 23A (see ?uid line 1000B) or second side 23B (see ?uid line 1000C) of adapter 23 to provide a ?uid communication path between the interior and exterior of enclosure 100 (?uid line 1000A is in a position to provide the ?uid communication path). id="p-155" id="p-155"
id="p-155"
[00155] Continuing to refer to alternatively, one or more pass—through(s) 1002 may be associated with line ?tting 1004 located on one or both of ?rst side 23A and/or second side 23B of adapter 23. Fitting 1004 may be any of a variety of ?ttings such as a barb ?tting, luer lock , quick connect ?tting, etc. One or more ?uid line 1000A, 1000B, 1000C, 1000D may be attached to ?ttings 1004 on adapter 23 to provide a ?uid pathway through pass-through 1002 to the exterior and/or interior of enclosure 100. Fluid lines 1000A, 1000B, 1000C, 1000D may each have a dedicated e or may be generic and utilized as a speci?c scenario es. In con?gurations where enclosure 100 is used in decellularization processes and other specimen engineering related applications, one or more of the ?uid lines may be a supply line through which ?uid may be supplied to the interior of enclosure 100. One or more of ?uid lines 1000A, 1000B, 1000C, 1000D may be a drain line via which ?uid may be drained or removed from the interior of enclosure 100. One or more of ?uid lines 1000A, 1000B, 1000C, 1000D may also be used for both supplying and ng ?uid. One or more of ?uid lines 1000A, 1000B, 1000C, 1000D may be a en line through which ?uid may be pumped to or from one or more biological specimen 162 ( such as a tissue. en(s) 162 ( may be any suitable group of cells and their surrounding extracellular matrix.
Specimen(s) 162 ( may also be a tissue, group, or groups of tissues such as an organ or organ system, e. g. a lung or lungs. Various rations may include differing numbers of lines. For example, different con?gurations may include a different number of ?uid lines 1000A, 1000B, 1000C, 1000D depending on the type of specimen 162 ( to be placed in enclosure 100. Using the example of an organ such as a lung, there may be three specimen lines (e. g. one for the pulmonary artery, one for the pulmonary vein, and one for the trachea) in on to a supply line and a drain line. The size of the ?uid conduit in ?uid lines 1000A, 1000B, 1000C, 1000D may depend, for example, but not limited to, on one or more of the following: en(s) 162 (, type/specimen, desired ?uid ?ow rate, desired ?ow impedance through the line, enclosure 100 size, adapter 23 size, ?tting 1004 size, and pass- through 1002 size.
Continuing to still further refer to enclosure 100 can provide a e closed environment for the specimen. Enclosure 100 can be suspended in a suspension ?uid, without sterilizing the suspension ?uid which may speed a decellularization process and may help augment ef?ciency. Suspending enclosure 100 in a suspension ?uid may e perfusion of ?uid throughout the Specimen(s) 162 (. The temperature of the suspension ?uid may be controlled which could aid in optimization of the decellularization process.
Referring now to ?rst adapter part 23C and second adapter part 23D may be included. First adapter part 23C may be attached to interior surface 21B of enclosure 100, second adapter part 23D may be attached to exterior surface 21A of enclosure 100. Each of ?rst and second adapter parts 23 C, D may include pass-throughs 1002 which may be aligned with one r when adapter parts 23C, D are coupled to enclosure 100. In some con?gurations, each of adapter parts 23C, D may include at least one ?tting 1004. At least one ?tting 1004 may only be included on a single side of each of adapter parts 23C, D. Fittings 1004 may be placed on faces of adapter parts 23C, D which may be non-adj acent when adapter parts 23C, D are attached to ure 100.
Referring now to enclosure 100 may be provided in a partially assembled or constructed manner. For example, enclosure 100 may be ed in le pieces (e. g. a ?rst and second part) or may be provided as a clamshell. Enclosure 100 may be a clamshell which includes ?rst part 100C which may be joined to second part 100D. In some con?gurations, ?rst part 100C may be continuous with second part 100D. Alternatively, ?rst part 100C may be attached to second part 100D along ?rst edge 100E, for example, but not limited to, by heat bonding, laser welding, ultrasonic welding, solvent bonding, or any other suitable attachment process. In some con?gurations ?rst edge 100E and one or more of second edge 100F, third edge 100G, or fourth edge 100H of ?rst part 100C may be attached to second part 100D of enclosure 100. Alternatively, for example in con?gurations in which enclosure 100 is round or not nal, n 20-80% of ?rst part 100C of enclosure 100 may be provided already joined to second part 100D of enclosure 100.
Continuing to refer to in some con?gurations, enclosure 100 may be provided as a clamshell with ?rst part 100C being continuous with second part 100D.
Additionally, an edge or portion of ?rst part 100C may be joined to second part 100D. At least one edge or portion of ?rst part 100C may be open or not joined to second part 100D. While ?rst part 100C is not tely joined or sealed to second part 100D of enclosure 100, ?uid lines 1000 may be fed through or attached to adapter 23. Adapter 23 may be d in any of the plurality of parts of enclosure 100. For example, adapter 23 may be located on second part 100D of the enclosure 100. ] ing now to once any ?uid lines 1000 have been attached or fed through adapter 23 to provide ?uid communication between an interior cavity 1150 ( in enclosure 100 and ?uid sources and reservoirs exterior to enclosure 100, ?rst part 100C and second part 100D of enclosure 100 may be joined creating a seal between interior cavity 1150 ( and the surrounding environment. Any parts of ure 100 may be joined together using any suitable process. In some con?gurations, enclosure 100 may be heat sealed or bonded together.
Referring now primarily to ure ?rst section 100A can include adapter 23 and any number of ?uid lines (eg. ?uid lines 311, 313, 315, 317, and 319).
Enclosure ?rst section 100A can further include exterior surface 21A, sealing surface 25, and or surface 21B. Supply/drain lines 311 and 319 can penetrate adapter 23 and can terminate at tubing connector 27. Supply line 319 and drain line 311 may supply ?uid to enclosure 100 ( and drain ?uid from ure 100 (. Supply line 319 and drain line 311 may supply ?uid and drain ?uid simultaneously. In some rations, a separate pass-through adapter or number of pass-through adapters (not shown) may be included for one or more line 311, 313, 315, 317, 319. Supply line 319, and drain line 311 for example can have a separate pass-through adapter or each have a separate pass-through adapter. Pass-through adapters may be placed, for example, but not limited to, on a portion of enclosure 100 opposite adapter 23.
Specimen line 313 can penetrate adapter 23 and can terminate at tubing connector 29 supplying ?uid to specimen 162 (. Specimen line 315 can penetrate adapter 23 and can terminate at tubing connector 31 supplying ?uid to specimen 162 (. Specimen line 317 can penetrate adapter 23 and can terminate at tubing tor 33, supplying ?uid to other parts of specimen 162 (. en lines 313, 315, 317 can also be used to drain ?uid from specimen 162 (. Tubing connectors 27, 29, 31, 33 may be any number of or a ation of tubing connectors such as quick connects, luer locks, or other line ?ttings. Fluid lines 319, 317, 315, 313, and 311 may, in some rations, have an outer diameters in the range of, for example, but not limited to, 0125-05 inch or smaller or larger. Fluid lines 311, 313, 315, 317, 319 may be silicone lines which may be interference ?t into pass-throughs 1002 ( in adapter 23.
Fluid lines 311, 313, 315, 317, 319 may have outer diameters slightly larger (eg. 1/8 inch larger) than pass-through 1002 ( ions such that a radial seal may be created when ?uid lines 311, 313, 315, 317, 319 are in place in hrough 1002 (. In some con?gurations, the inner diameters of ?uid lines 311, 313, 315, 317, 319 may be sized to be substantially equal the size of their respective pass throughs 1002 ( in adapter 23.
Still referring primarily to enclosure ?rst section 100A can be partially sealed to enclosure second section 100B () at sealing surface 25. Specimen(s) 162 ( (eg. target tissue or group of tissues, for example an organ) can be inserted into partially sealed enclosure 100 (. Specimen lines 313, 315, 317 may then be placed into communication with Specimen(s) 162 (. For example, tubing connectors 29, 31, and 33 may be attached to specimen connecting lines, such as, for example, specimen line 75. Partially sealed enclosure 100 ( can be completely sealed at sealing surface 25. After enclosure 100 ( is completely sealed, specimen(s) 162 (, for example, but not limited to, a lung, can proceed h a decellurization process, for example.
After tion of the decellularization process, specimen(s) 162 ( can remain within enclosure 100 ( for preservation, subsequent sing, and until use. For example, enclosure 100 may serve as a start to ?nish receptacle for a biological specimen 162 ( as it goes through a complete tissue or specimen ering process.
After preparation, the biological en 162 ( may remain in enclosure 100 until it is ready to be used for transplant. A biological specimen 162 may be put through a multi-step tissue or specimen engineering process ing, for example, decellularized, recellularized, and storage until use all within the same enclosure 100.
Referring now primarily to adapter 23 can be, for example, laser welded into enclosure ?rst section 100A, however any form of ?uid/liquid-tight coupling arrangement could be used, for example, ultrasonic g, other welding techniques, heat sealing or bonding, and gluing. In con?gurations in which adapter 23 is laser welded to enclosure 100, r 23 may be made, but is not limited to being made, of a al which is dark, black, or absorbs light at the desired welding wavelength. A seal between adapter 23 and enclosure 100 can also be pressure tight. Adapter 23 can be any thickness and size. For example, adapter 23 can measure 75" high x 1.25" wide x .25" thick, though in some con?gurations, adapter 23 need not be rectilinear and may take any shape. r 23 can be scalable relative to the size of the target tissue(s) or specimen(s) 162 (, the size of enclosure 100, and the size of any ?uid lines 311, 313, 315, 317, and 319, for example. Adapter 23 can be surrounded or embedded between layers of the enclosure 100 material, for example, but not limited to, layers of enclosure ?rst section 100A, or can be sealed to exterior surface 21A or or surface 21B ( of enclosure 100. Further, adapter 23 could include multiple layers, and the layers could be sealed to exterior surface 21A or interior surface 21B ( of enclosure 100. Adapter 23 may, in some con?gurations, include a ?rst portion and a second n with the ?rst portion attached to interior surface 21B ( of enclosure 100 and the second n attached to exterior surface 21A of enclosure 100 (see . Still further, adapter 23 could be molded into or over molded onto enclosure 100. Adapter 23 could be formed of high density polyethylene (HDPE), and may be made of a gamma sterilization compatible material. In other con?gurations, adapter 23 may be made of a material which may be heat sterilized for example, but not limited to, autoclaved or gas sterilized for example, but not limited to, with ethylene oxide without being degraded or compromised. In some con?gurations, adapter 23 is not required to be sterilized, which can increase the types of materials suitable for constructing adapter 23. ing now to adapter 23 can accommodate a suite of ?uid lines 311, 313, 315, 317, 319 ing tubing connectors 27, 29, 31, 33 such as quick connects.
Adapter 23 may, for example, but not d to, accommodate a supply (tubing connector 27), drain (tubing connector 27), and three specimen interfaces (tubing tors 29, 31, and 33).
Any number of tubing connectors and specimen interfaces can be accommodated, depending on the application and the specimen 162 ( size or type, for example. ing now to , a side View of an example of enclosure 100 is shown. Enclosure 100 may be sealed at sealing surface 25 and may include enclosure ?rst section 100A, enclosure second section 100B, and ?uid lines 319, 315, There can be more than two sections of enclosure 100, depending on the application. Enclosure 100 can be, but is not limited to being, constructed of a mixture of nylon and linear low density polyethylene (LLDPE).
The materials for enclosure 100 may be chosen ing on the desired durability, re ance, pliability, bonding/welding compatibilities, permeability, chemical compatibility, etc. of the material. In some con?gurations, enclosure 100 may be constructed of a multilayer material in which each strata of the multi-layered material can be chosen for a particular characteristic. Materials that are suitable for undergoing autoclaving, gamma sterilization, or other sterilization procedure can also be selected for manufacturing enclosure 100. Puncture- resistant materials can also be chosen, for e, the tage of nylon in a multilayer material including both nylon and LLDPE can be increased. The material used to uct enclosure 100 can be based on the chemicals that enclosure 100 could hold for the application.
For example, materials that are non-reacting with the chemicals could be chosen, or materials that have known reactions that are desirable for the applications could be chosen. Enclosure 100 could be coated on the inside or outside to affect permeability, for example enclosure 100 could include a metalizing layer. Multi-layer construction of enclosure 100 could incorporate le types of materials to accommodate n applications. In some con?gurations, adapter 23 ( and enclosure 100 may be constructed of compatible materials to enable coupling (e.g. ultrasonic or laser g) of adapter 23 ( to or within enclosure 100. For example, enclosure 100 could include an outer polymer layer and an inner polymer layer, where the layers could surround a nylon layer and potentially one or more other layers.
Referring now to , ure 1001 can include, but is not limited to including, multiple interior cavities 1150A, B. Enclosure 100, in a partially sealed state, can e ?rst enclosure portion 100J and second enclosure portion 100K. First ure portion 100] and second enclosure portion 100K may be sealed to one another at sealing e 25 and/or dividing sealing region 25A. Dividing sealing region 25A may be created to isolate interior cavities 1150A, B to prevent ?uid and/or liquid communication between interior es 1150A, B. Each of interior cavities 1150A, B may be associated with adapter 23 which can allow ?uid tubes, eg. ?uid lines 311, 313, 315, 317, 319, 71, 73, 75 that can be exterior and/or interior to cavities 1150A, B to be coupled to adapter 23.
Referring now primarily to , enclosure 1001 () is ed in a sealed state. First enclosure portion 100J and second enclosure portion 100K can be continuous with one another and form clamshell connected enclosure 100L. First enclosure portion 100J may be folded into contact with second enclosure portion 100K. A seal may then be formed between ?rst enclosure portion 100J and second enclosure portion 100K. In some con?gurations, a seal is formed between two enclosure portions 100J, 100K at ng sealing region 25A as shown in . After any specimen(s) 162 ( have been inserted and after any manipulation of ?uid tubes, e.g. ?uid lines 71, 73, 75 on interior of cavities 1150A (), 1150B (), interior cavities 1150A (), 1150B () may be completely sealed from the surrounding environment at various of sealing surfaces 25.
] Referring now primarily to A and B (which shows a detailed view of region A of A), interior surface 21B can include adapter 23. Various types of tubing connectors 27, 29, 31, and 33 may be introduced to the interior of ure 100 () via adapter 23. Tubing connectors 27 can be used, for example, for inlet and drain ?uid lines 71, 73 to deliver ?uid to and extract ?uid from enclosure 100 (). Fluid lines 311, 313, 315, 317, 319 ated with tubing connectors 27, 29, 31, 33 can be inserted into r 23 through ori?ces 28 in adapter 23. Ori?ces 28, for example, can be milled into adapter 23 for speci?c-sized lines or may be formed during molding of adapter 23. Alternatively, r 23 may be formed as a solid structure which can be welded to enclosure 100 ().
Ori?ces 28 may be added afterword. For example ori?ces 28 may be milled (e.g. drilled) or punched through enclosure 100 () and adapter 23 after welding the two together. In other con?gurations, enclosure or 21B can include, for e, but not limited to, pre-cut line holes which may align with ori?ces 28 milled, punched, formed, etc. in adapter 23.
Referring now primarily to , tubing connectors 27, 29, 31, and 33 can be provided at the al ends of ?uid lines 311, 313, 315, 317, 319 respectively. Fluid lines 311, 313, 315, 317, 319 can pass through r 23 at ori?ces 28. Depending on the ?uid line, or the con?guration, ?uid line 311, 313, 315, 317, 319 may be passed from the outside of enclosure 100 () to the interior of enclosure 100 () or vice versa.
Referring now primarily to , r 23 can provide a pass-through extending from exterior surface 21A to interior surface 21B of enclosure 100 (). Fluid lines 311, 313, 315, 317, 319 may extend through the pass-through to adapter 23.
Referring now to A and B (which shows a detailed view of region C of ), optional interior tubing connectors 27, 29, 31, and 33 can be of various types, depending on the application. For example, tubing connector 31 attached to ?uid line 315 can be large enough to odate an attachable ?uid conduit having an outer diameter of, for example, but not limited to, about 0.5 inch. Further, tubing connector 29 can be sized to accommodate a ?uid conduit having an outer er of, for example, but not limited to, about 0.25 inch. Tubing connector 33 can be sized to accommodate a ?uid t having an outer diameter of, for example, but not limited to, about 0.125 inch. After enclosure 100 () has been sealed at sealing surface 25, ?uid lines 311, 319 attached to tubing connectors 27 can deliver and extract ?uid from ure 100 () after the target specimen(s) 162 (, for example a lung, has been placed in ?uid communication with, for example, but not limited to, ?uid lines 313, 315, 317 via tubing connectors 29, 31, and 33.
Referring now to , enclosure 100 can be provided in a ?attened state where enclosure 100 has a small interior volume. Enclosure 100 may be later ?lled with ?uid, specimen(s) 162 (, and other materials when used. Additionally, enclosure 100 may be provided partially sealed to tate tion of tubing to and placement of specimen(s) 162 ( into enclosure 100. Enclosure 100 may be later completely sealed to isolate the interior volume of enclosure 100 from the exterior environment. Enclosure 100 may be manufactured with pre—forrned tubing holes 42. Enclosure ?rst section 100A can be sealed during manufacture to enclosure second section 100B at, for example, ?rst edge 41A and possibly second edge 41B, or vice versa.
Alternatively, and referring now to , in another con?guration, enclosure 100 may be provided as a clamshell with enclosure ?rst section 100A which is uous with enclosure second section 100B along ?rst edge 41A. Additionally, an edge or portion of enclosure ?rst n 100A may be joined to enclosure second section 100B. For example, enclosure ?rst section 100A and enclosure second section 100B may be joined along second edge 41B. At least one edge (eg. edges 41C, 41D) or portion of enclosure ?rst section 100A may be open or not joined to ure second n 100B.
] Referring now to FIGS. 19 and 20, adapter 23 having tubing ports 45 can be attached to enclosure ?rst section 100A. Enclosure ?rst section 100A can be perforated, for e, but not d to, after adapter 23 becomes attached to enclosure ?rst section 100A.
There can be any number and size of tubing ports 45, depending on the application. id="p-176" id="p-176"
id="p-176"
[00176] Referring now primarily to FIGS. 21 and 22, enclosure 100, sealed at sealing e 25, can include r 23 accommodating one or more barbed ?tting 47 for retaining, for example, but not limited to, a line such as any or a combination of ?uid lines 311, 313, 315, 317, 319 (). Barbed ?ttings 47 can be various shapes and styles, and can extend from a number of faces of adapter 23. For example, adapter 23 may include one or more barbed ?tting 47 for each ?uid line 311, 313, 315, 317, 319 () with which it may be associated. Adapter 23 may, for example, include barbed ?ttings 47 extending from adapter 23 to the exterior of enclosure 100.
Referring now primarily to , adapter 23 may instead or additionally include one or more barbed ?tting(s) 47 for retaining, for example, but not limited to, lines such as ?uid lines 71, 73, and 75 () disposed within the interior of the enclosure 100 (). As above, such ?ttings can be various shapes and styles and may extend from adapter 23 into the interior volume of ure 100 ().
Referring now to FIGS. 24 and 25A, a cross section of enclosure 100 taken at line 14-14 () is shown. Enclosure ?rst section 100A, may be sealed at sealing surface 25 to ure second section 100B. Adapter 23 may be attached to enclosure 100.
Adapter 23 may include one or more or barbed ?tting 47A and one or more interior barbed ?ttings 47B. Barbed ?ttings 47A, 47B may each include a lumen which may be in ?uidic communication with each other via a pathway in adapter 23. Tubing may be attached to each of exterior barbed ?ttings 47A and interior barbed ?ttings 47B to allow for ?uid to be erred into and out of enclosure 100.
Referring now primarily to B, a detailed view of region D of A is shown. Adapter 23 may be attached to one of interior surface 21B or exterior surface 21A of enclosure 100 (A). In some con?gurations, barbed ?ttings 47A, 47B can include stem 44 and barb 43. At least a n of barb 43 may have a larger diameter than stem 44. In some con?gurations, barb 43 may be a formed as a l frustum or series of stacked conical frustums. Stem 44 of each of barbed ?ttings 47A, 47B may be ed and retained within ori?ce 28 in adapter 23. Stem 44 of barbed ?tting 47A, 47B may also extend through enclosure 100 to either the interior or exterior of enclosure 100 depending on exterior/interior surfaces 21A, 21B r 23 is coupled to. Alternatively, barbed ?ttings 47A, 47B may be formed integrally with adapter 23 during manufacture of adapter 23. One or more exterior barded ?tting 47A or one or more interior barbed ?tting 47B can be omitted, depending on the application.
Referring now to , r 23 may include barbed ?ttings 47A, 47B on ?rst side or face 23A and second side or face 23B. Barbed ?ttings 47A, 47B may, for e, be projections including a stacked series of l frustums 43A, 43B, 43C, 43D.
Barbed ?ttings 47A, 47B may be sized to ?t a variety of different tubing sizes.
Referring now also to , ?uid lines 311, 313, 315, 317, 319, 71, 73, 75 may be connected to barbed ?ttings 47A (), 47B to establish ?uid communication ys between the interior and the exterior of enclosure 100. Including barbed s 47A (), 47B on the multiple faces of adapter 23 may allow at least some tubing connectors such as tubing connectors 27, 29, 31, 33 (B) to be omitted. Instead, ?uid lines such as ?uid lines 311, 313, 315, 317, 319, 71, 73, 75 may directly couple to adapter 23 via barbed ?ttings 47A (), 47B.
Referring now to A and B (which depicts a detailed view of region E of A), enclosure 100 may include adapter 23 having a number of tubing connectors 1100. Tubing connectors 1100 may be any of a variety of tubing connectors such as luer type connectors. Tubing connectors 1100 may be attached to adapter 23 via any suitable process and in some con?gurations may be welded, solvent bonded, attached with a ?xative, etc.
Similarly to barbed ?ttings 47A (), 47B (B), tubing connectors 1100 may be disposed on more than one side of the r 23. At least one tubing connector 1100 may be accessible to tubing located al to enclosure 100 and at least one tubing connector 1100 may be accessible to tubing disposed inside enclosure 100. Each of the ?uid lines which may be attached to the adapter 23 may include a ating mating structure which may mate with tubing connectors 1100 on the adapter 23. ing now primarily to , tubing connector 27A (which may be a quick connect) can attach to fluid line 71. Fluid line 71 may include mating body 71A which may mate into tubing connector 27A. Fluid may be delivered from reservoir 182 ( to the interior of enclosure 100 () via supply line 311 and ?uid line 71. Specimen line 75 may include a mating body 75A which may mate into tubing connector 29. Fluid may be delivered from oir 182 () to specimen 162 ( in enclosure 100 (FIG‘ 30) via line 313 and specimen line 75. Tubing connector 27B (which may be a quick connect) can attach to drain line 73 which can include at least one drain hole 53. Drain line 73 may include mating body 73A which may mate into tubing connector 27B. Drain line 73 may also include drain line end 51 which may include, for example, but not limited to, one or more positioner 54. Positioner 54 may in some con?gurations be a magnetic element and/or at least one weight. Magnetic elements may include magnets or materials which react to the presence of a magnetic ?eld such as certain rare earth metals, transition metals, or various alloys. If positioner 54 is a magnetic t, a magnet external to enclosure 100 () may be used to af?rmatively position drain line end 51. If positioner 54 is a weight, positioner 54 may be used to ely position drain line 73 at the bottom of enclosure 100 (FIG 30). If enclosure 100 () is repositioned (e.g. ?ipped over), positioner 54 may passively bring drain line 73 to a new on within enclosure 100 (). Positioners 54 may also be included at other ons on drain line 73 or may be included on other ?uid lines (e.g. ?uid and en lines 71, 75).
Positioners 54 may be attached to a ?uid line in any suitable . In some con?gurations, positioner 54 is interference ?t into drain line end 51. Alternatively, a weight, or metallic/magnetic element positioned 54 may be embedded in drain line end 51 (or at other locations) in drain line 73 (or other line) via, an overmolding process for example.
Referring now to , enclosure 100 which has been partially exploded is shown. In some con?gurations, interior surface 21B of enclosure 100 may include one or a number of straps or tethers 55. Tether(s) 55 may be used to tether or strap one or more lines (eg. drain line 73) in place duIing usage. Before enclosure 100 is sealed, the desired line or lines may be attached to or otherwise associated with tether 55 which in turn may be attached to or surface 21B of enclosure 100. The desired line or lines may, for example be placed into channel 55A n tether 55 and interior e 21B of enclosure 100. Flanking each side of channel 55A, tether 55 may be coupled to enclosure 100. Tether 55 may be attached to the bag using any method, for example, but not limited to, heat . id="p-185" id="p-185"
id="p-185"
[00185] Referring to , system 2100 for use in specimen engineering can include, but is not limited to including, one or more valve module 2019. Valve module 2019 can include pneumatic distribution assemblies 2025 which can be in ?uid communication with parts of ?uid circuit 2029 via ?uid conduits, a manifold or combination thereof for example.
Pneumatic bution assemblies 2025 may include one or more valves which may be ed to selectively place parts of ?uid circuit 2029 in communication with pressure supplied from pressure source 2011. Each pneumatic distribution assembly 2025 can include, for example, but is not limited to including, four or fewer . Pneumatic distribution assemblies 2025 may also e manifolds which may connect valves of pneumatic distribution assembly 2025 to a common bus or buses. Pressure source 2011 may e ?uid at one or more positive pressure and one or more negative pressure. Pressure regulator 2051 may be included to help regulate pressure from pressure source 2011. Pressure source 2011 may provide pressure at positive and negative pressure rail (e. g. -500mmHg and 900mmHg) which may be individually stepped up or down by regulator 2051 to other pressures. The pressures may d or additionally be stepped up or down by ting the opening of valves of pneumatic distribution assemblies 2025 such that the pressure supplied at a part of ?uid circuit 2029 is maintained at a desired value. tic distribution assemblies 2025 may include one or more pressure sensor.
Referring again to , controller 2047 may control the ?ow of ?uid through ?uid circuit 2029, for example, to/from enclosure 100. ller 2047 can provide commands to valve module 2019 control try 2039 which can pump ?uid through system 2100. Controller 2047 can communicate commands to valve module 2019 through PCAN (CANbus interface) 2043, and can receive information about ?uid pathway 2029 and the ?uid n from sensors 2027. Sensors 2027 can include, but are not limited to including, temperature, pressure, conductivity, leak ion, -line, ?ow rate, level sensors, and weight sensors. Controller 2047 can calibrate pressure sensors through CANbus 2043, update pressure readings, and display ?ow diagram valve pressures. Though the example con?guration uses CANbus interface 2043, any other communication interface may be used.
Continuing to refer to , ller 2047 may be initialized by setting default values 3059 (B) for parameters used during, for e, but not limited to, the decellularization s. In some configurations, default values 3059 (B) can be provided for the usage of ure 100 and filtered levels of reservoirs 182 (. t values 3059 (B) can also be provided for volumes such as, for example, but not limited to, pump volumes and pump volumes to/from enclosure 100. Default values 3059 (B) can be further ed for times such as, for example, but not limited to, delayed operation start time, delayed operation current time, pump start time, last reservoir swap time, and last run time.
Default values 3059 (B) can also be provided for toggles such as, for example, but not limited to, resume in progress, stop in progress, was paused, bolus required, and overrides.
Toggles 3057 (B) can be lized to, for example, but not limited to, false, off, true, and on. Default values 3059 (B) can be provided for states such as, for example, but not limited to, mixing state, solution pump operating state, and bolus state, and modes such as pressure mode, flow mode, time control mode, volume control mode, and bolus control mode.
Default values 3059 (B) for certain parameters can be initially set such as, for example, but not d to, fill pressure (for example, -225 mmHg), delivery pressure (for example, 600 mmHg), minimum ?ow (for example, an alarm level such as 25 ml/min), maximum flow, ?ow rate (for example, as fast as possible such as 975 ml/min), minimum re (for example, an operational limit such as -200 mmHg), maximum pressure (for example, an operational limit such as 550 mmHg), flll pressure in ?ow mode (for example, -100 mmHg), delivery pressure in ?ow mode (for example, 100 mmHg) minimum ?ow in ?ow mode (for example an alarm level such as 25 ml/min), maximum flow in ?ow mode (for example an alarm level such as 500 ml/min), ?ow rate in pressure mode (for example a limit such as 100 ml/min), minimum pressure in pressure mode (for example a limit such as -100 mmHg), and maximum pressure in pressure mode (for example a limit such as 100 mmHg).
Continuing to refer to , valve module 2019 may also include control circuitry 2039 providing, for example, but not limited to, control s and power to pneumatic distribution lies 2025. Control circuitry 2039 may include one or more processor 2038 which may provide commands to pneumatic distribution assemblies 2025. In some con?gurations, separate control circuitry 2039 for each pneumatic distribution assembly 2025 may be included. Valve module 2019 may include one or more valve module of the type disclosed in US. Provisional Patent Application serial number ,351, ?led December 12, 2014, and entitled Modular Valve Apparatus and System, Attorney Docket No. P33 which is hereby incorporated by reference herein in its entirety.
] Referring again ily to , controller 2047 can connect to processor 2038 through CANbus interface 2043, and can locate devices in valve module 2019, in ular at least one pneumatic distribution assembly 2025 that can be connected through CANbus interface 2043 to controller 2047. Controller 2047 can locate at least one pneumatic distribution assembly 2025 by sending CANbus es and awaiting replies, repeating the message send and waiting cycle up to, for example, ?ve times. The response time can be, for example, but not limited to, .005-.01 seconds. Controller 2047 can count the number of pneumatic distribution assemblies 2025 that are located by tracking the number of pneumatic distribution assemblies 2025 that respond to the CANbus message. After devices are found, controller 2047 can execute a step—by-step decellularization according to, for example, but not limited to, recipe 2047A (A), and in addition, controller 2047 can accept override commands from, for example, but not limited to, GUI 2037 (A). ing now to A, controller 2047 can icate with, for example, but not limited to, sensors 2027, GUI 2037, controller communications 2043, and recipe 2047A either directly or through communications network 2047X. Some con?gurations can include 2—way communications between recipe 2047A and controller 2047, as well as 2—way communications n GUI 2037 and controller 2047. In some con?gurations, controller 2047 can read and modify recipe 2037 either statically or cally. Further, controller 2047 can receive information from GUI 2037, such as, for example, recipe override information, and can supply ation to GUI 2037 as the system proceeds h decellularization and/or recellularization processes. Some con?gurations can e 2-way communications between GUI 2037 and recipe 2047A. In some con?gurations, GUI 2037 can read and modify recipe 2047A when, for example, a step, precondition, pressure, port, ?ow rate, mode, and/or duration is entered into GUI 2037 that differs from recipe 2047A. Some con?gurations can include 1- way communications between recipe 2047A and ller 2047 in which controller 2047 can read, but not modify, recipe 2047A. Some con?gurations can include 2-way communications among all of recipe 2047A, GUI 2037, and controller 2047. In some con?gurations, controller 2047 can direct ?uid ?ow based on both recipe 2047A and GUI 2037 by receiving information from recipe 2047A and/or GUI 203 7, reconciling con?icting commands dynamically, opening/closing valves, and starting/stopping pumps based on the reconciled ds. In some con?gurations, controller 2047 can dynamically update GUI 2037 while receiving commands from GUI 2037. In some rations recipe 2047A can be isolated from changes attempted through GUI 2037, and can be isolated from modi?cations attempted by controller 2047.
Referring again to A, controller 2047 can manage valve activity, for example, g and closing valves, based on recipe 2047A, GUI 203 7, and the automatic sing of controller 2047. The states of valves 216A-Z, 218A-R ( can include, but are not limited to including, open, closed, and disabled. In some con?gurations, there can be, for example, but not limited to, ?ve types of valves 216A—Z, 218A—R (: positive 2—way r valves, negative 2-way chamber valves, 3-way ?uid valves, pressure sensor valves, and unused valves. Some valve functions that can be performed and the tic processing that can be performed with respect to the functions are set out in TABLE 11.
Valve function Automatic nrocessin_ Update mixing valves (1) update mixing count (2) if mixing count is greater than 6, reset mixing count, set mixing active to false and inlet valve open to false, also close all open mixing valves (3) insure solution pump is not bypassed (4) block a pause state (5) warn if reservoir has failed to ?ll in the expected number of Close all open valves (except (1) update valve states atmospheric re and (2) close ?uid valves reservoir pressures) (3) close mixing valves reported as open (all valves on oir input side except atmosphere and reservoirs-in) (4) handle water solenoid valve specially (5) disable internal mixing valve control logic 6 close all non-mixin_ valves reoorted oen all valves on the —reservoir out to/from um s ba or drain Set static valves and start (1) close any open valves pumps for operations (2) open the valves used for this step (3) set up for special bolus ions (4) close reservoir-outs that may be open (5) determine the solution to be used for this step (6) open valves for this step (7) con?gure and start the perfuse and exchange pumps for this step, for example, set mode, set ?ll pressure, set ry pressure, set minimum ?ow rate, set maximum ?ow rate, set target ?ow rate, set minimum pressure, set maximum pressure, set number of strokes (8) allow for zero values in recipe 2047A for unused mode parameters (9) set mirror mode of (10) get pump run status (11) update display for any pump in non-idle state including frozen, mirror mode off (12) start perfuse/exchange pumps only if pump con?guration is not mode off and if exchange/perfuse pump con?guration is mode off (13) when both pumps are active and if system 2048B is in mirror mode then set the mode to exchange mirrors (14) e a modi?ed ?ow rate = target ?ow rate * pre- selected scale / 100 (15) set the modi?ed rate to a flow rate limit if the modi?ed rate > ?ow rate limit (16) start both perfuse and exchange pumps, both pumps can be running and neither as mirror — start both by con?guring both with type, ?ll re, delivery pressure, and target flow rate (17) recompute bag ion for both pumps ' override arameters TABLE II Referring again primarily to A, controller 2047 can log data, for example pressure data. To maintain the size of the log, controller 2047 can trim excessive old ?rst elements off the log while adding new data to the end of the log. ller 2047 can decide dynamically or statically which elements to trim. Controller 2047 can also adjust the logging sample rate, for example, based on the amount of memory available. Errors, email information, valve status, pump con?guration, pump status, control status, reservoir status, preconditions, recipe step status, priming status, starting and stopping decellularization/recellularization, GUI selections, logging status, solution status, override status, bolus status, ure status, recipe load status, hardware status, and system state can be logged. Logged data can be accessed by selected logging tab 3211B (D).
Referring ily to B, controller 2047 can recognize internal sing modes 3055 or states 3051/3 049 that can guide execution of recipe 2047A (A). System 2048B can enter active states 3051 such as are listed in Table III. In Table III, some of the many active states 3051 to which system 2048B can enter are listed along with the status of GUI buttons/boxes (B) and intra/inter process communication ?ags (F). When state 3051 is associated with processes (P) or other states (S), a required status of the process and/or state to enable active state 3051 to be properly entered is shown.
B/F/S/P Not Disconnect hw push button enabled connected, Connect to hw push button enabled i.e. not Start push button d connected Stop push button enabled state Pause push button enabled Skip step push button enabled Jump to step push button enabled Add note push button enabled Restart step push button enabled s running s pause Process ready to proceed Select ?le push button enabled Restore state push button enabled Save ?le push button enabled Toggle sequence edit push button enabled uush button enabled Connected Disconnect hw push button enabled True but no recipe Connect to hw push button d False 2047A (FIG. Set up chambers 31A) has Stop all pumps Ready To Run1 been loaded, Logging enable check box enabled True i.e. connected Logging rate hertz double spin box True state enabled True Organ connector check boxes enabled True Bag check box enabled True Pump check boxes enabled False Start push button enabled False Stop push button enabled wwwwwwwwwwewwwwwwwmmwwwwwwwwww False Pause ush button enabled False pumps should be active, this should take a second or two to complete Skip step push button enabled wwwwn—mewww False Jump to step push button enabled False Add note push button enabled True t step push button enabled False Process g False Process pause False Non mixing valve overridden True Process ready to proceed True Select ?le push button enabled True/False2 Restore state push button enabled True Reoort ooum states ush button enabled Prime lines Disconnect hw push button d and enclosure Connect to hw push button enabled 100 (FIG. Start push button enabled 31F), i.e. Stop push button enabled prime Pause push button enabled operations Skip step push button enabled state Jump to step push button enabled Add note push button enabled t step push button enabled Process running Process pause Process ready to proceed Select ?le push button enabled Report pump states push button enabled Restore state ush button d Connected Disconnect hw push button enabled True and ready to t to hw push button enabled False run, i.e. ready Solution level con?gure to run state Insure that all open valves are closed Reset pump control settings Ready To Run3 Start push button enabled True Stop push button enabled False Pause push button enabled False Skip step push button enabled True Jump to step push button enabled True Add note push button enabled True Restart step push button enabled False Process running False Process pause False Non—mixing valve overridden False Process ready to proceed True Select ?le push button enabled True Reoort ooum states ush button enabled wwwwwwwwwwwwwwwwwwwwwmmwwwwwwwwww True 2 True if there is a saved state file 3 Set the state of all valves in the valve reported states list to close valve, then close all valves Restore state push button d True/False Toggle sequence edit push button enabled True Set exchange/perfuse/inlet/solution pump Set Various control con?uration Parameters5 Running, i.e. Pump valve override Reset Pump s Disconnect hw push button enabled True g state Connect to hw push button enabled False Enable override active reservoir ion False7 Start push button enabled False Bolus Stop push button enabled True required and Pause push button enabled True bolus Skip step push button d False delivery not Jump to step push button enabled False complete Add note push button enabled True state Restart step push button enabled True Process running True Process pause False Select ?le push button enabled False Save ?le push button enabled False e state push button enabled False Toggle sequence edit push button enabled False Pause i.e. Disconnect hw push button enabled True process pause Connect to hw push button enabled False state Start push button enabled True Stop push button enabled True Pause push button enabled False Skip step push button enabled True Jump to step push button enabled True Add note push button enabled True Restart step push button enabled True Process running False Process True Process Disconnect hw push button enabled True complete, i.e. Connect to hw push button enabled False process Stop all pumps wwwvwwwmmwwwwwwwwwwwwwmmwwwwwwwwwww Process complete8 te Execute stop sequence Stop all pumps9 state Insure that all open valves are closed s complete10 Start push button enabled False Sto. ush button enabled False 4 True if there is a saved state file Parameters are type, fill pressure, r pressure, minimum pressure, maximum pressure Reset pump diagnostics when a recipe is started 7 Block manual override of active reservoirs when running No pumps should be ninning, this can take a second or two to complete 9 And valve actions Close all valves in the valve reported states Pause push button enabled B Skip step push button d B Jump to step push button d B Add note push button enabled B Restart step push button enabled B Process g F Process pause S Non mixing valve overridden F Ready to proceed F Process control ?le loaded F Select ?le push button enabled B Save ?le push button enabled B Restore state push button enabled B Toggle sequence edit push button enabled B Perform Disconnect hw push button enabled B True precondition t to hw push button d B False 3203 (FIG. Stop all pumps P Process complete12 31F) (empty e stop sequence P Stop all pumps13 reservoir, ?ll Insure that all open valves are closed P Process complete14 reservoir, Start push button enabled B False connecting to Stop push button enabled B True hardware) i.e. Pause push button enabled B True preconditions Skip step push button enabled B False for transient Jump to step push button enabled B False state Add note push button enabled B True Restart step push button enabled B False Process running F False Process pause S True Non mixing valve overridden F False Ready to proceed F True Process control ?le loaded F False15 Select ?le push button enabled B True Save ?le push button enabled B False Restore state push button enabled B False Toggle sequence edit push button enabled B False Set reservoirs to dual or single depending B on parameter settings Get the solution for the active step Dis la status bun: TABLE III Force a reload of the file for the next n No pumps should be running, this can take a second or two to complete 13 And valve actions 14 Close all valves in the valve reported states Force a reload of the file for the next session Referring again primarily to B, ller 2047 can connect to hardware using, for example, a process that can include, but is not limited to including, if CANbus 2043 (A) is disconnected, ller 2047 can connect CANbus 2043 (A), start control of system 2048B, and read the hardware con?guration before a search for devices is initiated. Controller 2047 can wait, for example, for twenty seconds for system 2048B to respond. Controller 2047 can also update hardware status by getting the status of any of pumps 202, 204, 206, 208, 210, 212, 214 (, getting the level of reservoirs 182A/B (F), and showing the status of any of pumps 202, 204, 206, 208, 210, 212, 214 ( to be frozen/idle. Controller 2047 can also reset hardware through hardware tab 3211A (D). if CANbus 2043 (A) is connected, ller 2047 can reset resettable items in system 2048B, reset state 3051 to CANbus disconnected, update CANbus display and status display, and update the state of GIU 2037 (A).
Continuing to refer to B, other states 3051/3 049 and substates 3053 can be entered, such as, for example, but not limited to, process g state, process paused state, process complete state, control system ready, control system con?guring pumps, control system executing command, and unexpected state. Controller 2047 can process conditions such as waiting for completion of, for example, reservoirs ?lling or other system events to occur. Controller 2047 can indicate certain ongoing events such as reservoir ?lling and/or emptying and bolus delivery, and an indication of the status of a speci?c reservoir. There can be a transient state, a ditions state, that can be induced while controller 2047 awaits precondition 3203 (D) such as, for example, but not d to, priming or ?lling reservoir 182A/B (F) in preparation for a next of steps 3201 (D) of recipe 2047A (A). ller 2047 can e certain ions to be true, and certain conditions to be met before new or next state 3049 can transition to active state 3051. Modes 3055 and substates 3053 can be subject to r ia. In addition to states 3051/3049, controller 2047 can associate processing steps with substates 3053 such as, for example, but not limited to, idle, emptying reservoirs 182A/B (F), waiting on hardware, ?lling a single reservoir 182A/B (F), ?lling dual reservoirs 182A/B (F), and running using reservoir x while ?lling reservoir y. id="p-196" id="p-196"
id="p-196"
[00196] Continuing to refer to B, controller 2047 can execute steps ated with modes such as time control mode, volume control mode, and bolus control mode.
If recipe 2047A (A) dictates that the system is in volume control mode, controller 2047 (A) can access a ?ow rate of liquid traveling through the system, for example, by user input, and compute an approximate time that step 3201 (D) will e such as, for example, but not limited to, time = V*60/FR, where V: volume 3215 and FR = ?ow rate. In some con?gurations, the approximate time can be padded, by for example 5%, to avoid underestimating the volume. If recipe 2047A (A) dictates that the system is in time control mode or bolus mode, controller 2047 (A) can access, from recipe 2047A (A), duration 3213 (D) required for step 3201 (D). Controller 2047 (A) can set an imate time for a bolus to complete. In some con?gurations, the bolus time can be approximately sixty seconds.
Referring now to B, system 2048B can enter the s running state when it begins executing the steps of recipe 2047A (A). Controller 2047 can lize state and total pause times to, for example, zero, and start time of recipe 2047A (A) to, for example, local time. The steps of recipe 2047A (A) can each include a duration. Starting and ending times of each step can be determined based on the start time of recipe 2047A (A). Each step 3201 (D) could also have preconditions 3203 (D), which can be checked and ful?lled before step 3201 (D) is executed. If recipe 2047A (A) is restarted, or if another recipe 2047A (A) is loaded, controller 2047 can perform housekeeping such as, for example, setting an appropriate active state 3051. To pause and resume recipe 2047A (A), except in certain circumstances such as, for example, when the pausing or ng is from step 3201 (D) in which g is occurring, preconditions 3203 (D) can be checked for next step 3201 (D).
Automatic changes of state 3049/3051 and other processing of states 3049/3051 can be blocked while in a paused state. Controller 2047 can stop any of pumps 3225-3228 (F), for example, but not d to, before ding to next step 3201 (D) in recipe 2047A (A), as a part of recipe 2047A (A), as a part of an error condition, and as part of a manual override. For example, a stop button may be pressed during preconditions 3203 (D) for step 3201 (D) of recipe 2047A (A). Several toggle switches 3057 such as, for example, but not limited to, mixing valve overridden, wait for reservoirs to be full and empty, and empty both reservoirs, can be used to provide information about the activity of pumps 3225-3228 (F). After ng the information switches, controller 2047 can stop some of pumps 3225-3228 (F), and can insure that some ofvalves 216A-Z, 218A—R (, depending on the requirements of recipe 2047A (A), are closed. Pumps 3225- 3228 (D) can take, for example, a few seconds, to complete g.
Referring still to B, ller 2047 can set an intended next processing state 3049. In some con?gurations, controller 2047 can move system 2048B from expected next state 3049 to active state 3051 as shown in Table IV.
Active state New state Other contin_enc Result Process complete Allow change, state Process abort or sto Not connected Connected Process control ?le Allow change, (recipe) not loaded Process not ready to roceed Not connected Connected Process control ?le Set ready to run state, reci oe loaded Allow chane Not connected Ready to run Hardware connected Allow change Connected Read to run Allow chane Process complete Ready to run Process control ?le Allow change reci oe loaded Ready to run Process running Init state/total pause time, recipe start/end time, Check preconditions, Allow chane Process running Process pause Set state before pause, Allow chane Process ause Preconditions Allow chan_e Process running Process abort or stop Allow , Don’t wait for reservoir empty/full, Don’t empty both reservoirs, Stop all pumps, Insure that all open valves are closed TABLE IV Referring still primarily to B, ller 2047 can update active state 3051, i.e. manage changes of state 051, for example, multiple times/second. When 16 Set this ?ag to communicate to other processes that the system is prepared to allow a change of state in volume mode, controller 2047 can also adjust the projected end time of a step of recipe 2047A (A) after, for example, twenty strokes based on, for e, the time the last ten strokes took. Controller 2047 can set chamber volumes for each of pumps 202, 204, 206, 208, 210, 212, 214 ( through CANbus interface 2043. Controller 2047 may not be able to update active state 3051 if system 2948B is not ready to proceed, and this can happen when prerequisite conditions such as emptying and ?lling reservoirs 182 ( are being performed. A bolus may be handled differently. If recipe 2047A (A) has been completed (i.e. if system 2048B is in process complete state), then controller 2047 may not need to test preconditions, and ller 2047 can set substate 3053 to idle. Otherwise, if system 2048B is not in process complete state, and if system 2048B is not ready to proceed, controller 2047 can check for state change preconditions being met, and, if system 2048B is ready to proceed and active state 3051 is not the same as next state 3049, then controller 2047 can set active state 3051 to next state 3049 and then update GUI 2037 (A).
Continuing to refer primarily to B, controller 2047 can update the progress of each step of recipe 2047A (A). In some con?gurations, controller 2047 may not update the progress when system 2048B is in prime operations state, or when system 2048B is in pause state if state 3051/3049 before pause state was prime operations state. Controller 2047 can compute the time that the step requires to run if the mode is time control mode and if system 2048B is running, and can set state 3051/3 049 to s complete if the step is 100% complete, active state 3051 is running, and the number of steps has reached its maximum on the current of active steps 3051. ise, ller 2047 can reset control settings of any of pumps 202, 204, 206, 208, 210, 212, 214 (, send e-mail if necessary, and change to the next step of recipe 2047A (A) (all of pumps 202, 204, 206, 208, 210, 212, 214 ( may be stopped at this time). Controller 2047 can insure that there are several seconds of accumulation before setting the actual volume to prevent stale data from ing volume steps if in volume l mode, and can update s when needed for volume control mode steps.
Controller 2047 can move system 2048B to process complete state when, for example, the step is 100% volume complete and active state 3051 is process running, and recipe 2047A (A) has come to a last of active steps 3051. Otherwise if the process is not complete, controller 2047 can reset l settings of any of pumps 202, 204, 206, 208, 210, 212, 214 (, send e— mail if necessary, and go to next active step in recipe 2047A (A). If an error is detected, controller 2047 can issue an error alert. Controller 2047 can increment the state and the total pause times, reset the times on change of step or start of process, and update progress bars on GUI 2037 (A) if system 2048B has moved to process complete state. ] ing again to B, controller 2047 can update an active sequence to, for example, periodically update a step change in recipe 2047A (A) as well as update pause information and updates to progress bars 3205 (G). ller 2047 may not complete the update if active state 3051 is pause or prime state and if next state 3049 is not not-connected and not connected. If the step of recipe 2047A (A) has changed and the start time of the step is not zero, controller 2047 can set the step end time to be the step start time plus the time the step is to require. If system 2048B is in time mode, controller 2047 can direct GUI 2037 to display, for e, a ?rst progress label. If system 2048B is in volume mode, controller 2047 can direct GUI 2037 to display a second progress label. If system 2048B is in bolus mode, controller 2047 can direct GUI 2037 to display a third progress label. Otherwise, controller 2047 can direct GUI 2037 to display an alert message and complete recipe time label 3207 (G). If system 2048B is paused, controller 2047 can compute an end time of the step as the current time plus the time left to complete the step, and the end time of recipe 2047A (A) as the time the step started plus the total remaining time in the step plus the total time the step was paused. If system 2048B is in mirror mode, controller 2047 can determine and ?ag conditions that froze both pumps or in which system 2048B was not able to be resumed. ller 2047 can determine and log actual s reported by any of pumps 202, 204, 206, 208, 210, 212, 214 (.
Referring still primarily to B, if a ?rst of pumps 202, 204, 206, 208, 210, 212, 214 ( is ahead ofa second of pumps 202, 204, 206, 208, 210, 212, 214 (, controller 2047 can unfreeze the second of pumps 202, 204, 206, 208, 210, 212, 214 ( by resuming processing of system 2048B and vice versa. ller 2047 can reduce the mirror-delta to a 1-pod size delta at the end of the step of recipe 2047A (A) (when almost at the target volume), and then compare the ?ow rates of the ?rst and second of pumps 202, 204, 206, 208, 210, 212, 214 ( to a freeze set amount (mirror delta limit) to decide if either of the ?rst or second pumps 202, 204, 206, 208, 210, 212, 214 ( should be frozen.
Controller 2047 can then resume processing when one of pumps 202, 204, 206, 208, 210, 212, 214 ( is frozen. In some con?gurations, both of the ?rst and second of pumps 202, 204, 206, 208, 210, 212, 214 ( may not be frozen at the same time. Controller 2047 can reduce mirror delta limit by half (preventing the reduced limit from being less than one pod volume).
When the second of pumps 202, 204, 206, 208, 210, 212, 214 ( is ahead and is , then controller 2047 can wait for the second of pumps 202, 204, 206, 208, 210, 212, 214 ( to be halfway ahead. When the ?rst of pumps 202, 204, 206, 208, 210, 212, 214 ( is ahead and frozen, controller 2047 can wait for the ?rst of pumps 202, 204, 206, 208, 210, 212, 214 (FIG, 2) to be half way behind. Controller 2047 can issue a warning if the volume error is greater than a mirror alarm delta spin box value (not shown). Controller 2047 can direct GUI 2037 (A) to update progress bars 3205/3207 (G) managed by GUI 2037 ( 31A) based on volume or time control modes, update a bolus ss bar managed by GUI 2037 (A) based on bolus state (bolus init stopping pumps 3101 (C), bolus partial drain reservoir 3103 (C), bolus deliver solution 3107 (C), bolus ?ush 3111 (C), bolus delivery complete 3109 (C)), e time to complete step 3201 (F) of recipe 2047A (A) based on progress bar 3205/3207 (G) managed by GUI 2037, and update step table y 3047 (F) managed by GUI 2037 (A) if a row of the recipe table has changed.
Referring still primarily to B, controller 2047 can receive from GUI 2037 direction to force a step state. If system 2048B had been in ready state and is moved to run state, controller 2047 can execute actions ing to a depression of start button 3211 (F) and pause button actions. Also, controller 2047 can e the override stop s 3213A (D) when system 2048B is started or d. To complete the forcing of a step state, controller 2047 can set an initial start time of step 1, set active state 3051 to process running, set a sleep time, freeze all of pumps 202, 204, 206, 208, 210, 212, 214 (, pause from process running, skip the step that had been selected before start was selected, set the non- mixing valve so that it is not overridden, pause from running, stop/abort all of pumps 202, 204, 206, 208, 210, 212, 214 (, change to a specific step, and set the requested of states 3051.
In some configurations, controller 2047 can load, save, update, and restore a last saved of states 3051/3 049.
Referring again primarily to B, controller 2047 can set system 2048B in an update not ready to proceed substate for as long as active state 3051 is not ready to proceed, and can issue a warning if active state 3051 is ready to proceed. To update the not ready to d substate, if active state 3051 is prime operations state, or if active state 3051 is process pause state, system 2048B may not enter the update not ready to proceed substate. For updating the not ready to d substate, automatic state changes can be blocked if system 2048B is in pause state. Further, controller 2047 can set substate 3053 to idle and active state 3051 to ready to proceed if next state 3049 in recipe 2047A (A) is either connected or ready to run, and if l system state 3063 is ready and CANbus 2043 is connected, which can be the prerequisite conditions for changing to a ted state (normal ?ow) or a ready to run state (if recipe 2047A (A) is loaded before connecting). Otherwise controller 2047 can set active state 3051 to not ready to proceed and sub state 3053 to waiting on hardware. If next state 3049 in recipe 2047A (A) is the pause state, other state processing can be blocked. ller 2047 can check for an empty of reservoirs 182 (, a ion that can further stop all of pumps 202, 204, 206, 208, 210, 212, 214, 216 ( that are active according to recipe 2047A (A) if one or more of reservoir(s) reservoirs 182A/B (F) has just been emptied. Further, controller 2047 can also check if reservoirs 182A/B (F) are full and can also set ?ags but may not start mixing. Still further, controller 2047 can further mark reservoirs 182A/B (F) as currently ?lling and the same reservoir 182A/B (F) or a different reservoir 182B/A (F) as currently being used.
Continuing to refer primarily to B, controller 2047 can process step 3201 in recipe 2047A (A) by executing the following steps. (1) Initialize, while system 2048B is idle, active step 3201 in recipe 2047A (A), the maximum number of steps 3201 in recipe 2047A (A), the total processing time in recipe 2047A (A), the elapsed step time of active step 3201, the last saved time of active step 3201, and the times per step 3201 (duration 3213) to completion of step 3201. (2) Reset data, while system 2048B (A) is idle, for example, reset total processing time 3213 of step 3201, reset the total number of steps 3201, reset the elapsed step time, reset the last saved time, reset active step 320], reset the maximum number of steps 3201, reset the times per step 3201 to completion of step 3201, reset step target volume to one (for example, initialize the step target volume to above the step actual volume 3215). ller 2047 can determine the step volume % complete, and can reset step actual volume 3215. (3) Set/get the maximum number of steps 3201 (system 2048B is idle when setting the maximum number of steps 3201. (4) Change active step 3201: (a) set the elapsed step time to zero and set the last saved time to the current time. (b) If the number of active steps 3201 is lower than the maximum number of steps 3201, set active step 3201. (c) If the same step 3201 is being restarted, reset the start time. (d) When step 3201 is either being changed or restarted, controller 2047 can set up GUI 2037 (A), clear a on pump blocked ?ag on every step change, set the actual step volume to zero, reset all of pumps 202, 204, 206, 208, 210, 212, 214, 216 (FIG, 2) and valves 216A-Z, 218A-R ( that may have been left in an indeterminate state from the previous of steps 3201, and check preconditions 3203 for the next step of recipe 2047A (A), and update the progress of step 3201.
Continuing to still refer primarily to B, controller 2047 can also perform utility functions such as, for example, but not limited to, (1) determine active step 3201 of recipe 2047A (A), (2) perform certain tasks when system 2048B is in a particular substate, such as, for example, logging system status when system 2048B is in substate idle, waiting on hardware, emptying reservoirs 182A/B (F), ?lling single reservoir 182A or 182B (F), ?lling multiple reservoirs 182A/B (F), running single reservoirs 182A or 182B (F), using ?rst reservoir 182A (F) and ?lling second reservoir 182B (F), and using second reservoir 182B (F) and ?lling ?rst reservoir 182A (F), (7) determine the current te, (8) determine the next active step of recipe 2047A (A), (9) move system 2048B to the next active step of recipe 2047A (A), (10) move system 2048B to a speci?c step 3201, (11) restart the active step of recipe 2047A (A), (12) perform step time and number of steps accounting, (13) set step 3201 as complete, (14) determine total remaining time, not including pause time, in the step of recipe 2047A (A), (15) determine the total elapsed time, (16) get the elapsed time taken by the step of recipe 2047A (A), (17) determine the percent complete of the step in terms of time, (18) set the time step 3201 completed, (19) determine the t complete of step 3201 in terms of , (20) determine step target volume, (21) set step target volume, (22) determine the step actual volume 3215, (23) set step actual volume 3215, (24) determine total sing time for all steps 3201 of recipe 2047A (A), (25) determine the total t complete of recipe 2047A (A) based on d time, (26) determine the amount of time that step 3201 required, and (27) t step 3201 of recipe 2047A (A) by disabling sequence edit, disabling the sequence edit push button, restarting active step 3201 of recipe 2047A (A), checking if e- mail needs to be sent, and resuming from a paused state.
] Referring to B, in some con?gurations, controller 2047 (A) can receive log data 3061 such as, for example, but not limited to, of valve pressure, pump stroke count, mixing count, and ?uid ?ow rate. Valve pressure refers to the pressure sensed by at least one of sensors 2027 of valves , 218A-S (. In some con?gurations, the number of valves can be thirty-?ve, and the number of pump valves can be twenty-eight. Pump stroke count refers to the number of strokes required for a pump to take to support the ?uid ?ow required by recipe 2047A (A). Pump stroke count can be initialized to a ular value and can vary throughout the duration of step 3201 of recipe 2047A (A). Mixing count refers to the number of strokes required of solution/inlet pumps 3225/3227 (F) to create a ?uid required by recipe 2047A (A). In some con?gurations, the number of pumps, not ing, for example, a waste pump, can be four. Mixing count can be initialized to a particular value and can vary hout the duration of step 3201 of recipe 2047A (A).
Fluid ?ow rate refers to the rates of ?uid ?ow through the system based on the requirements of recipe 2047A (A). Fluid ?ow rate can be initialized to a particular value and can vary throughout the duration of step 3201 of recipe 2047A (A).
] Referring primarily again to B, when controller 2047 determines that a ?rst type of error has occurred, controller 2047 can enter an error processing state in which current activity can be stopped, an indication that stopping is complete can be requested and received, and the user can be noti?ed that an error has occurred, for example, by email. When controller 2047 determines that a second type of error has occurred, controller 2047 can enter a warning sing state in which controller 2047 can, for example, but not limited to, pause the system and await user interaction. ller 2047 can perform such housekeeping as clearing ?ltering on reservoir levels to prevent a reservoir over-full condition from immediately posting after the clearing as a result of hysteresis in the signal produced by the sensor detecting the reservoir level. Other alerts can include, but are not limited to including, overfull tank, mixing error, CANbus error, solution error, recipe ?le error, state error, connection timeout, communications problem, operation problem, unexpected state, and ive volume.
Referring primarily to C, controller 2047 (B) can process a bolus sequence. Controller 2047 (B) can manage delivery of the bolus in a con?guration in which there are le of reservoirs 182A/B (F). Bolus delivery 3100 can include steps such as, for e, but not limited to, initializing 3101 bolus delivery 3100 including stopping pumps in which pumps 202, 204, 206, 208, 210, 212, 214 ( can be stopped, and system 2048B (B) can pause while the effect of the stopping pumps completes. Bolus delivery 3100 can include partially ng 3103 reservoir l82A/B (F). If the bolus can ?t into available space in reservoirs 182A/B (F), controller 2047 (B) can direct 182A/B (F) to be drained. Bolus delivery 3100 can include con?guring 3105 any of valves 216A-Z, 218A-S ( for a bolus. Con?guring 3105 can include closing all open mixing valves including reservoir-in , g up accounting of solution 190 (G) for the bolus, and displaying valves 216A-Z, 218A-S ( in their correct states on the display of GUI 2037 (A)). Con?guring 3105 can include ?ushing a bolus. Flushing a bolus can e con?guring a bolus ?ush, g for valves 216A—Z, 218A-S ( to be updated, ?ushing the bolus, and g for valves 216A-Z, 218A-S ( to complete processing.
Bolus delivery can include delivering 3107 the bolus solution. If the bolus volume and rinse volume can ?t into 182A/B (F) without over?ow, the number of strokes to deliver the volume of the bolus can be determined, and mixing to reservoirs 182A/B (F)) can be d. Bolus delivery can include completing 3109 the bolus delivery by updating the volume to indicate that the bolus is done. Delivering 3111 a bolus ?ush, for example, using a ?rst of pumps 202, 204, 206, 208, 210, 212, 214 ( only, not a second of pumps 202, 204, 206, 208, 210, 212, 214 (, can e, but is not limited to including, ring strokes = (volume of ?ush after bolus + pod size)/2/pod size, ?ushing the bolus based on ?rst pump strokes in and second pump strokes in, mixing to reservoirs 182A/B (F), computing the ?rst pump flow rate and the second pump ?ow rate, opening the inlet valve, con?guring the bolus ?ush, setting the second pump start time, and starting mixing. Mixing can be started directly because the correct of valves 216A-Z, 218A-S (FIG 2) are open. The ?rst of pumps 202, 204, 206, 208, 210, 212, 214 ( can be pre-con?gured for bypass mode. Bolus states 3100 do not have to occur in the order set out in C.
Continuing to refer primarily to C, determining the number of s to deliver the volume can include calculating a ?rst pump stroke in as (target volume + pod size)/2/pod size, delivering the bolus based on the ?rst pump stroke in and a second pump stroke in, setting ?rst and second pump ?ow rates, closing selected of valves 216A-Z, 218A-S ( associated with second of pumps 202, 204, 206, 208, 210, 212, 214 (, updating the ?rst pump start time, and starting mixing based on the ?rst and second pump flow rates.
Updating ?ow rate values can include determining stroke numbers for each of pumps 202, 204, 206, 208, 210, 212, 214 (. Before the last stroke, controller 2047 can compute the solution ?ow rate ?lter ml/min = ((stroke count — last ed stroke count) * pod size * 60)/(current time — stroke start time)) for solution pump 3225 (F) and update display 4224A (F), for example. Controller 2047 (B) can a compute solution flow rate in ml/min. If the current pump stroke number is smaller than last pump stroke number, controller 2047 can reset the ?ow rate and ated ?ow rate parameters. Controller 2047 (FIG 31B) can update the flow rates for all of pumps 202, 204, 206, 208, 210, 212, 214 (, update all last stroke numbers, and set ?ow rate to zero for pumps 202, 204, 206, 208, 210, 212, 214 ( 2) that are idle.
Continuing to refer to C, con?guring a bolus ?ush can include, but is not limited to including, g all of valves 216A-Z, 218A-S ( that have been open from bolus delivery 3100 ing reservoir-in valves. Con?guring a bolus flush can also include setting a bypass of solution 190 (F), opening selected of valves 216A—Z, 218A-S ( pre-selected for this step, setting system 2048B (B) in bypass mode so pumping can be done through a second of pumps 202, 204, 206, 208, 210, 212, 214 ( such as, for example, inlet pump 3227 (F), for dual oirs 182A/B (F), delivering the bolus into oir 182A/B (F), setting up accounting for solution 190 (F), and displaying valves 216A-Z, 218A-S ( in their correct states. The ting usage for on 190 (F) can be con?gured using a ?rst of pumps 202, 204, 206, 208, 210, 212, 214 (, such as solution pump 3225 (F), so the flush is not d as the bolus solution.
Referring now primarily to D, and with respect to recipe 2047A (A) and recipe override, recipe 2047A (A) can be displayed as a list of steps 3201, for example, as shown in GUI recipe display 3047. Controller 2047 (B) can select/load/save a ?le that includes recipe 2047A (A) that can be, but is not limited to being, a comma-separated values ?le. Controller 2047 (B) can read a loaded ?le that includes recipe 2047A (A) and can interpret from recipe 2047A (A) actions that controller 2047 (B) can take to complete, for example, decellularization of biological specimen 162 (F). Each step of recipe 2047A (A) can, but does not always, require preconditions 3203 to be met.
Continuing to refer primarily to D, controller 2047 (B) can access, from recipe 2047A (A), from which port 3214 to draw liquid in order to ful?ll the requirements of step 3201. s can include solutions or sources 190 (F), for example, as set out in Table 1. Controller 2047 (B) can access, from recipe 2047A (A), pump information such as ?uid s 4214 and ?uid targets 4216 of pumps 3226/3228 (F), and ?ll pressure 4220 and delivery pressures 4222 of pumps 3226/3228 (F).
Pump sources 4214 can e, but are not limited to including, ?uid from enclosure 100 (F) and ?uid from storage reservoirs 182A/B (F). Pump s 4216 can include, but are not d to including waste reservoir 180 (F) and a port of biological specimen 162 (F). Recipe 2047A (A) can also set pump mode 4218 which can include mirror mode in which pumps 3226/3228 (F) operate cooperatively.
Continuing to still further refer primarily to D, ller 2047 can receive recipe override information from recipe display 3047. Pump and valve instructions can be overridden, depending on the states of buttons and boxes on recipe display 3047, for example.
Selection of reservoir 182A/B (F), level of solution 190 (F), pump valve, chemical levels, and pump actions can also be overridden by setting override parameters 3221 (F). Examples of pump de parameters can include inlet pump stop 3213A and perfuse pump stop 3249. If inlet pump stop 3213A is selected from recipe display 3047, and if step 3201 of recipe 2047A (A) requires an action of inlet pump 3227 (F), the action of recipe 2047A (A) can be overridden. If perfuse pump stop 3249 is selected from recipe display 3047, and if step 3201 of recipe display 3047 requires an action of one of pumps 3226/3228 (F) that is perfusing biological specimen 162 (F), the action of recipe 2047A (A) can be overridden. Inlet pump 3227 (F) and pumps 3226/3228 (F) can be restarted through recipe display 3047, again overriding recipe 2047A ( 31A). Recipe 2047A (A) can be overridden with respect to, for example, but not limited to, valves , 218A-S (, solution levels of s 190 (F), and storage reservoirs 182A/B (F).
Continuing to refer primarily to D, controller 2047 (B) can test the integrity of the recipe and the current con?guration, for example, but not d to, the ing tests. Controller 2047 (B) can check that steps 3201 are in a correct sequence order, and that port 3214 is not set to "no tanks" when one of pumps 3226-3228 (F) needs to draw from at least one of reservoirs 182A/B (F). Controller 2047 (B) can check that both of pumps 3226/3228 (F) are not set to mirror mode, or that one of pumps 3226/3228 (F) is set to mirror mode and the other of pumps 3226/3228 (F) is off. Controller 2047 (B) can check that bolus volume is not ive compared to a pre-selected value, and that the bolus is not con?gured in a step of recipe 2047A (A) that has a ?ll precondition 3203. ller 2047 (B) can check that required parameter ?elds are not set to zero, that mixing is not disabled, and that pumps 3226-3228 (F) that are con?gured to use reservoirs 182A/B (F) are not part of a bolus. Controller 2047 (B) can check that a bolus into reservoir 182A/B (F) for recipe step 11 and recipe step n+1 does not empty reservoir 182A/B (F) as a pre-condition to prevent emptying the bolus before using it. Controller 2047 (B) can insure that valves 216A-Z, 218A—S ( are open to empty reservoirs 182A/B (G).
Continuing to still r refer to D, controller 2047 (FIG‘ 31B) can enable and disable editing of the sequence of recipe 2047A (A). In some con?gurations, editing can be accomplished through recipe display 3047. In some con?gurations, editing can happen automatically as a by—product of system ty. In some con?gurations, GUI (A) can accept, and controller 2047 (B) can automatically process, several types of instructions such as, for example, but not limited to, instructions with respect to state/substate 3049/3051/3053, solution 190 (G), valves 216A—Z, 218A-S ( 2), recipe 2047A (A), pumps 3225-3228, reservoirs 182A/B (G), and display features. GUI (A) can accept instructions to set the system in, for e, ready to run state and s complete state, and can report the state the system is in. GUI (A) can also accept instructions to set the level of solution 190, and to block a manual override of active of reservoirs 182A/B (G). Through GUI 2037 (A), a user can close the open ones of valves 216A—Z, 218A—S (, enable/disable display push buttons, and stop the usage of ure 100 (G). GUI 2037 (A) can further accept instructions to stop pumps 3225-3228. This list is not exhaustive, GUI 2037 (A) can accept a wide variety of instructions, a subset of which is described .
Referring still primarily to FIG‘ 31D, controller 2047 (B) can insure that preconditions 3203 for each of steps 3201 have been met. For example, after moving to step 3201, controller 2047 (B) can test if step 3201 requires ng solutions 190 (F) in reservoir 182A/B (F), get active step 3201, get target volume 3215 for step 3201 ifin volume or bolus of modes 3055, ifin time control of modes 3055 set duration 3213, set substate to idle, set ready to proceed to false. After all preconditions 3203 are met, controller 2047 (B) can start mixing if needed and start the active states 3051 (B) of selected of valves 216A-Z, 218A-S ( and pumps 202, 204, 206, 208, 210, 212, 214 (. If in bolus of modes 3055, controller 2047 (B) can disable mixing, use the same of reservoirs 182A/B (F) for ?lling and using, and set up for dual or single of reservoirs 182A/B (F). Controller 2047 (B) can also bypass ditions 3203 if, for example, the system is starting from a saved state.
Referring now primarily to E, controller 2047 (B) can manage priming by performing functions as set out in TABLE V.
Primin_ o.eration Actions taken b controller 2047 A Set state 3051/3 029 (FIG. Set active of states 3051 (B) to prime operation state 31B) for priming if active of states 3051 (B) is either ready to run or connected Update prime status Unblock solution pump 3225 (F) and insure that valves are closed if the prime ion succeeded k solution pump 3225 (F) and insure that valves are closed if the orime oeration failed Update solution only prime Update clock if mixing is running status Unblock solution pump 3225 (F) and insure that valves are closed if mixin; is not g Update empty fill oir If a drain and fill operation beginning through, for example, prime status but not limited to, a click on drain then ?ll button 3405, and if any of reservoirs 182A/B (F) is not empty, drain reservoirs 182A/B (F) If draining multiple reservoirs 182A/B (F), multiple of pumps 3226/3228 (F) can be used If any of pumps 3226/3228 (F) are , close open non-mixing of valves 216A-Z, 218A-S ( Fill reservoirs 182A/B (F) and unblock solution pump 3227 (F) If reservoirs 182A/B (F) are not full, close open of valves 216A-Z, 218A-S . for failure notice Prime mixing fill reservoir Determine flow rates of solution pump 3227 (F) and 182A/B (F) inlet pump 3225 (F) Insure that open of mixing valves , 218A-S ( are closed includin; reservoir—in valves If water 192 (F), compute inlet pump strokes as 1000/in1et pump size Insure that valves for reservoir 182A/B (F) are open If water 192 (F) and solution 190 (F), start mixing If water onl start inlet .
Prime lines changed If GUI 2037 (A) receives certain signals (representing, for example, user input), the status (for example, connected and clamped) of prime lines to enclosure 100 F can be uidated Prime pre-reservoir lines If GUI 2037 (A) receives n signals (representing, for example, user input through selecting prime pre-tank lines button 3401), controller 2047 (FIG 31A) can ' ' start ore-reservoir circuit _ _ Prime solution lines If GUI 2037 (A) receives certain s (representing, for example, user input through selecting prime solution lines button 3403), controller 2047 (A) can prime lines connecting solutions 190 (F) to pumps 228 F Prime post-reservoir lines that If GUI 2037 (A) receives certain signals, controller do not feed enclosure 100 2047 (A) can prime selected eservoir lines that F do not feed enclosure 100 F Prime enclosure lines If GUI 2037 (A) receives certain signals, controller 2047 (A) can prime lines connecting selected lines to ure 100 TABLE V Referring primarily to F, controller 2047 (B) can load a solution con?guration ?le that can set the names of solutions 190, set the concentrations of ons 190, set the capacities of solutions 190, and set the defaults (not shown) of ons 190 as set out for example in TABLE VI.
SDS 1X 100 Heoarin 10X 100000 100000 PBS 100000 Saline 100000 Other 100000 TABLE VI Controller 2047 (B) can update the solution ?le by allowing names, concentrations, and capacities of solutions 190 to be set, and controller 2047 (B) can save the solution ?le.
Controller 2047 (B) can resize the solution tanks and can update the solution ?le with the new sizes, if desired. Controller 2047 (B) can determine solutions 190 that are currently in use by determining current step 3201 (D) of recipe 2047A (A), and determining a temporary mixing state (for example, mixing ed, mixing Di water only, and mixing als and Di water). If the system is in bolus control mode, controller 2047 (B) can discontinue determining solutions 190 that are currently in use. If the system is not in bolus control mode, controller 2047 (B) can set mix parameters for solution 190 for t step 3201 (D) of recipe 2047A (A), and set up accounting information for the current of solutions 190. Controller 2047 (B) can also set mix ters for solution 190 for the current step of recipe 2047A (A) by, if not in bolus control mode, determining the active step of recipe 2047A (A), ing a residual oir level, computing a current volume in strokes as, and computing inlet strokes. Controller 2047 (B) can exit without setting the mixing parameters if the difference between the inlet strokes and current volume in strokes is less than zero.
Continuing to refer primarily to F, controller 2047 (B) can also set solution mix parameters by blocking on pump 3225 if source tration is 1X.
Controller 2047 (B) can determine a residual % of reservoir 182A/B, a current volume in strokes at least based on the volume of oir 182A/B and the pod size of inlet pump 3227, and the current inlet strokes based on volume of reservoir 182A/B and the pod size of inlet pump 3227. Controller 2047 (B) can compute the difference between the inlet strokes and the current volume in strokes and the volume. If the source concentration is not 1X, controller 2047 (B) can unblock solution pump 3225 if necessary and access values of inlet strokes, solution strokes, and volume. Controller 2047 (B) can update levels of solutions 190 periodically to, for example, update solution reservoir usage against a maximum capacity that can be, for example, user configured. In some configurations, if next state 3049 (B) is s running or ready to run or connected, controller 2047 (B) can determine and display levels of solutions 190. Controller 2047 (B) can update the levels of solutions 190 by computing the remaining of solution 190. Controller 2047 (B) can also update the tank ratios of ons 190 when, for example, a user selection has been made. Controller 2047 (B) can further set for which solution 190 accounting should be done. Solution pump 3225 and/or inlet pump 3227 can be used for accounting.
Referring primarily to F, controller 2047 (A) can direct GUI 2037 (A) to update valve images 3223 and diagnostic display images at the display of GUI 2037. For example, the display of images of valves 216A-Z, 218A—S ( can vary depending upon r any of valves 216A-Z, 218A-S ( are open or closed, for example, or whether any of valves , 218A-S ( are in unexpected states. Controller 2047 (A) can update the states of valves 216A-Z, 218A-S ( after the hardware is connected, i.e. when active state 3051 is not either connected or not connected. ller 2047 (A) can determine the state of any of valves , 218A-S ( in system 2048B (B), for example, atmospheric pressure , reservoir pressure valves, or ?uid valves.
Controller 2047 (A) can toggle valves 216A-Z, 218A-S ( between open and closed states. GUI 2037 (A) can update valve diagnostic images if the display of valve pressures is d. In some con?gurations, the current valve stic image can be updated periodically. Valves 216A-Z, 218A-S ( can be set to open/closed states based on, for example, pre-selected thresholds, and the type of valve. The valve display images can be updated after valves 216A-Z, 218A-S ( have been toggled. Controller 2047 can, for example, check if pumps 202, 204, 206, 208, 210, 212, 214 ( have been running for greater than a pre—selected time.
Referring again primarily to F, controller 2047 (A) can direct GUI 2037 (A) to update chamber image displays depending on, for example, but not limited to, pumps 202, 204, 206, 208, 210, 212, 214 (, the pump valve state (open or closed), and whether overrides for pumps 202, 204, 206, 208, 210, 212, 214 ( are allowed. Pump images can be updated depending on, for example, but not limited to, the type of pump 202, 204, 206, 208, 210, 212, 214 ( (for example, but not limited to, inlet, solution, exchange, e), whether pump 202, 204, 206, 208, 210, 212, 214 ( is responsive, whether pump 202, 204, 206, 208, 210, 212, 214 ( is running, whether the status of pump 202, 204, 206, 208, 210, 212, 214 ( has changed, and whether pump 202, 204, 206, 208, 210, 212, 214 ( is frozen. Solution pump 3225 can have more states than, for example, inlet pump 3227 (F). In some con?gurations, GUI 2037 (A) can update the display periodically, for example, but not limited to, about 3.33 times/second, and can update the animation of ?uid line 2029 if there have been s. In some con?gurations, GUI 2037 (A) can periodically update, for example, but not limited to, about every 1.7 seconds, ys and cs of pressure readings and solution levels, can check for reservoir 182A/B over full, ?ow rate values, ?ow rate display, diagnostic images, step progress, volume of enclosure 100, mixing valves (if system 2048B (B) is in s running state, preconditions state, prime operations state, ready to run state, or process pause state), last saved state (if active state 3051 is s g or preconditions). In some con?gurations, GUI 2037 (A) can alert an operator if active of states 3051 (B) is connected and more than, for example, two seconds have elapsed since a valve command or a pump command has issued. In some con?gurations, GUI 2037 (A) can test for a low memory event by testing against a low memory limit every, for example, ten minutes, and can take remedial action, for example, but not limited to, adjusting the rate of logging system events.
Referring again primarily to F, controller 2047 (B) can update the volume of enclosure 100 if the volume is being d by one of pumps 3226/3228 and if system 2048B (B) is not in pause state. The volume of enclosure 100 can be reset, perhaps after a delay, in some con?gurations to zero, when controller 2047 (B) sends a new command as the result of a next step in recipe 2047A (A) or an override through GUI 2037 (B). ller 2047 (B) can compute the volume of enclosure 100 based on the reported volumes of pumps 3226/3228 and whether or not ?uid is ?owing from 3226/3228 to or from enclosure 100. Controller 2047 (B) can recompute the ?uid direction from/to enclosure 100 and toggle the status of pumps 3226/3228 depending on whether pumps 3226/3228 are the source of ?uid to enclosure 100 or the target of ?uid from enclosure Referring again primarily to FIG‘ 31F, pumps 202, 204, 206, 208, 210, 212, 214, 216 ( can be set to l states that can include, but are not limited to including, dual pump state, single pump state, idle, start pumping, deliver chamber x or y, ?ll chamber x or y, deliver from chamber x or y while ?lling chamber y or x, ?lling chamber y while delivering to r x, EOS delay, frozen, initial ?ll, ?ll chamber state, ?lling, initial delivery, pump inactive, pump running, solution pump normal, solution pump bypass, on pump blocked, and delivering. In some con?gurations, the volume of pumps 202, 204, 206, 208, 210, 212, 214, 216 ( can be, for example, 308ml, which can require seven strokes to ?ll for a 43ml pod. ller 2047 (B) can update the pump start time, enable or disable pump diagnostics, and con?gure mixing. In some con?gurations, controller 2047 (B) can, when mixing is not running, con?gure mixing by con?guring solution pump 3225 and inlet pump 3227, setting pressure limits, con?guring pump commands based on mode ?ow, inlet pump ?ll pressure, and solution pump ry pressure, and setting mixing con?guration strokes for selected of valves 216A—Z, 218A-R ( based on solution pump strokes in and inlet pump strokes in.
Referring again ily to F, controller 2047 (B) can start mixing pumps by starting mixing of deionized (Di) water 192 and/or ons 190 to reservoirs 182A/B. Controller 2047 (B) can set inlet pump 3227 and solution pump 3225 ?ow rates, and set pumps 3227/3225 in flow mode. If mixing is disabled, controller 2047 (B) can discontinue setting up mixing. If mixing Di water only, controller 2047 (B) can update inlet pump start time, and start inlet pump 3227 at an inlet ?ow rate. If mixing chemicals and Di water, controller 2047 (B) can set pump start times for solution pump 3225 and inlet pump 3227, and start mixing at a solution ?ow rate and an inlet flow rate. If mixing directly from chemicals, controller 2047 (B) can set inlet pump start time, start inlet pump 3227, and block solution pump 3225. Controller 2047 (B) can pause to give mixing time to start.
Continuing to refer ily to F, controller 2047 (B) can stop pumps 3226-3228. If a stop is in progress, ller 2047 (B) can discontinue trying to stop pumps. If a stop is not in progress, controller 2047 (B) can stop the g recipe sequence and pause while pumps 3226-3228 receive the message. Controller 2047 (FIG, 31B) can test if any of pumps 3226-3228 are running and, if they are, controller 2047 (B) can abort each of pumps 3226—3228 individually because any of pumps 3226-3228 that are not responding to a stop command could be frozen. To make sure pumps 3226-3228 have stopped, ller 2047 (B) can check pump states by messaging over CANbus 2043 (B) and setting up an error path if any of pumps 3226—3228 have not stopped. uing to refer primarily to F, controller 2047 (B) can freeze pumps 3226-3228, if a freeze is not in progress, and can pause to give pumps 3226-3228 time to respond to the freeze command. Controller 2047 (B) can determine pump states by messaging CANbus 2043 (B) to determine if any of pumps 228 is running, and exit if none of pumps 3226-3228 is running. Controller 2047 (B) can freeze running pumps 3226-3228, get the status of pumps 228 by messaging over CANbus 2043 (B) test to make sure the freeze worked, and report errors if necessary. Controller 2047 (B) can also resume frozen of pumps 3226-3228 if a resume is not in progress, and if there are frozen of pumps 3226-3228. Controller 2047 (B) can pause to give the frozen of pumps 3226-3228 time to respond to the resume command. If the frozen of pumps 3226-3228 are non- mixing pumps, but the pumps are in mirror mode and set as non-frozen, controller 2047 (B) can resume pumps 3226/3228 less of their status in mirror mode.
Referring again primarily to F, controller 2047 can manage reservoir activity based on recipe 2047A (A), GUI 203 7, and the automatic processing of controller 2047. Some functions that ller 2047 can perform and the automatic processing lO performed by controller 2047 with respect to the ons are set out in TABLE VII.
Reservoir function Automatic urocessin; Partially drain reservoirs (1) if a sequence is running or the l system state is not control system ready then stop all pumps 202, 204, 206, 208, 210, 212, 214 ( and compute the number of strokes to drain the reservoir (2) if the number of strokes to drain oir 182A/B is greater than the maximum number of strokes from reservoir 182A/B then set the number of strokes to drain reservoir 182A/B to the maximum number of strokes (3) open a selection of valves 216A-Z, 218A-S ( that have to do with emptying oir 182A/B (4) update pump start time (5) start emptying oir 182A/B (6) set con?guration data for freeze and resume states while em t in_ reservoirs 182A/B Empty reservoirs (1) if a sequence is running or the control system state is not control system ready then stop all pumps 202, 204, 206, 208, 210, 212, 214 ( and compute the number of strokes to empty reservoirs 182A/B to be the maximum number of strokes times the filtered reservoir level d by 90 plus pad empty strokes (2) if the number of strokes to drain reservoirs 182A/B is greater than the maximum number of strokes from reservoir l82A/B then set the number of strokes to drain reservoir 182A/B to the maximum number of strokes (3) open a selection of valves , 218A-S ( that have to do with emptying oir 182A/B (4) update pump start time (5) start emptying reservoir 182A/B (6) set configuration data for freeze and resume states while em t in reservoirs 182A/B Emt multi le reservoirs at 1 if a seuence is runnin, or the control 5 stem state is not the same time control system ready then stop all pumps 202, 204, 206, 208, 210, 212, 214 ( and compute the number of strokes to empty both oirs 182A/B (2) if the number of strokes to drain reservoir 182A/B is r than the maximum number of strokes from reservoirs 182A/B then set the number of strokes to drain reservoirs 182A/B to the maximum number of strokes (3) open a selection of valves 216A-Z, 218A-S ( that have to do with emptying reservoir 182A/B (4) update pump start time (5) start emptying reservoir 182A/B (6) set con?guration data for freeze and resume states while ng reservoirs l82A/B using le of pumps 208, 210, 212, 214 ( simultaneously Empty active reservoirs (1) close any open of valves 216A-Z, 218A-S ( that are mixing valves (2) close all non-mixing valves that are open (3) command reservoirs 182A/B to drain (4) wait .25 seconds to give pumps 208, 210, 212, 214 ( time to start to t ?lling reservoirs 182A/B before the empty starts, Con?gure oir—in valves (1) close all solution valves that may be open and mixing (2) get current solutions (3) if not mixing chemicals and if reservoir level is too high then exit (4) open reservoir inputs, for example, open valves 216A-Z, 218A-S ( for input from a select one of reservoirs 182A/B if le of reservoirs 182A/B and the current ?lling of reservoirs 182A/B is the select one of reservoirs 182A/B (5) open selected of valves 216A-Z, 218A-S ( for solution 190 (G) (6) open inlet pump to mixing valves and water solenoid valves (7) con?gure mixing for solution pump stroke in and inlet pump strokes in if mixing one solution and state is mixing chemicals and Di water (8) if not mixing direct DiRO (i.e. the mixing state is mixing DI water only), open inlet pump to mixing valves and water solenoid valves and con?gure mixing for solution pump stroke in and inlet pump strokes in (9) if not mixing but instead drawing directly from solution 190 (G) (i.e. the mixing state is mixing direct from chemicals) then open inlet pump from solutions valves and inlet pump to mixing valves and con?gure mixing for solution stroke in and inlet strokes in (10) then start mixing pumps (i.e. starts mixing to reservoirs 182A/B (11) either start mixing or start inlet pump only for direct solution and direct DiRO water TABLE VII Continuing to refer primarily to F, during processing, controller 2047 (B) may check for when reservoir 182A/B is full. Controller 2047 (B) may wait for reservoir 182A/B to be full, for example, if ller 2047 is not also waiting for reservoir 182A/B to be empty, for example, in the case of drain before re?ll. Controller 2047 (B) may reset ?ags that indicate waiting for either reservoir 182A or 182B to be full if controller 2047 (B) is both waiting for oir 182A/B to be full and checking for the level of reservoir 182A/B to be full. Controller 2047 (B) can also (1) test if the reservoir level of a particular of reservoirs 182A/B is below a threshold to t mixing if the mixing state is not mixing disabled, (2) test against an empty reservoir pre-selected threshold, (3) test against a full reservoir pre-selected threshold, (4) test if reservoir 182A/B is ll and issue a warning if (a) system 2048B is neither in a connected state or a not connected state, and if a ?ltered level of reservoir 182A/B is greater than an alarm threshold, (5) test if reservoir 182A/B is empty if ller 2047 (B) is g for reservoir 182A/B to be empty, and controller 2047 (B) can stop all pumps if reservoirs 182A/B are emptied. Controller 2047 (B) can insure that reservoir valves are reset to a known state. Possible erations for resetting reservoir valves can include, but are not limited to including, atmosphere pressure, reservoir half pressure, and reservoir half in.
Referring now to FIG‘ 31G, in some con?gurations, GUI 2037 (A) can process selected user button depressions as laid out in TABLE VIII.
Automatic actions Start 3211 (1) disable pump override stop buttons that may have been enabled on any start or resume (2) restart certain of pumps 208, 210, 212, 214 ( if they were paused (3) allow the user to reset all non-mixing of valves 216A-Z, 218A-S ( to the previous state, ie. the state before the pause (4) resume all frozen of mixing pumps 204, 206 ( (5) resume the process g state if the state before the pause state is process running state and if the state before the pause was not d by an override command (6) restore the running state before the pause state that had been modi?ed by an override command (7) restore the state that was not d by an override d by, for example, ng all of pumps 202, 204, 206, 208, 210, 212, 214 ( (8) resume from prime operations when state 3051 is prime operations state (9) set the solution pump bypass and block state to solution pump normal (10) set an initial start time of the ?rst step of recipe 2047A (A) 11 move s stem to a orocess runnin; state Stop 3235 ( 1) prompt the user for veri?cation that a system stop is desired (2) send an e—mail or r form of electronic communication (3) move system to a process complete state Pause 3237 (1) clear any valve override change ?ag (2) trigger a pop-up window on valve state change (3) save the state before the paused state (4) freeze all pumps (5) send an email 6 move s stem to ause from runnin_ state Skip step 3239 (1) get next step to determine step to skip (2) disable sequence edit (3) check email (4) process specially if skip step button was pressed before start button (5) move to the active step after the step to skip if the maximum number of stes of reci e 2047A A have not been oerformed Exit application (1) if active state 3051 (B) is anything but not connected, verify that 3241 the user wants to exit the application (2) stop all activity by pumps 202, 204, 206, 208, 210, 212, 214 ( and valves 216A-Z, 218A-S ( Override (1) set sliders to reservoir default ons solution levels (2) con?gure solution level equal to resize bottles 3243 (3) update defaults from GUI 2037 if they have not been overridden manually ure the chemical reservoir size based on % in reservoirs Override pumps (1) stop all activity of pumps 202, 204, 206, 208, 210, 212, 214 ( and 3245 valves 216A-Z, 218A-S ( OR (2) override pumps 202, 204, 206, 208, 210, 212, 214 ( and compute inlet flow rate at ?ow rate de (1) set all pump con?guration values to user-selected values solution and/or (2) if on or inlet pump is running then prompt user to verify that a inlet pump recon?guration is desired 3243/3243A (3) stop all activity of pumps 202, 204, 206, 208, 210, 212, 214 ( and valves 216A-Z, 218A-S (FIG, 2) (4) if active state 3051 is not running, then override any of pumps 202, 204, 206 ( (5) start mixing to reservoirs 6 set ?ow rates (7) update pump start time (8) start mixing de (1) set con?guration values of all of pumps 208, 210, 212, 214 ( to perfuse/exchange user-selected values pumps 3245 (2) compute the current volume pumped plus any earlier volume pumped (3) if any of pumps 208, 210, 212, 214 ( are running, then prompt the user to verify that a recon?guration is desired (4) con?gure a selected of pumps 208, 210, 212, 214 ( by supplying any of type, ?ll pressure, delivery pressure, minimum pressure, maximum (5) update pump start time (6) start either perfuse or ge function 7 set function start time Generic override (1) set the enable/disable state of the UI pump override controls pump parameters (2) hide the pump override controls that are not used in the selected mode Solution pump (1) If the system is in any of states solution pump bypass, solution pump bypass and block blocked, and solution pump normal, set solution pump operating state state 3247 Generate mouse (1) keep recipe 2047A (A) active step row highlighted over step click to table changes if the bioreactor window is not the application with the center mouse/keyboard input focus (2) generate the mouse click event if the current active tab is associated with reci .6 2047A 1A Stop (1) stop running the process if a stop is in progress perfuse/exchange (2) stop all pump and valve actions and update exit if no pumps are running, abort all pumps, send stop to all frozen pumps, display exit if CANbus reports pumps are not running, test again if pumps are running and report an error if true TABLE VIII Continuing to refer ily to G, other functions that GUI 2037 (A) can process can include, but are not limited to including, going to step N 3249, g to step N via a pop-up window, adding a button, processing an e—mail setting button 3253, ding pumps/valves 3255, overriding oir con?gurations, ding reservoir selections, enabling/disabling speci?c valve state controls, modifying recipe 2047A (A), ?lling (on a graphical display) reservoirs 182A/B in use, graphing functions, calibrating pressure ditions push button, CANbus 2043 (B) and connection status display, updating (on a graphical display) the status of the system, and sing various push buttons. GUI 2037 (A) can manage a reservoir active check box by setting the current ?lling reservoir and the current using from reservoir to be the same in a le reservoir system where only a single oir is running. GUI 2037 (A) can, for example, set the active of reservoirs l82A/B to blue, the inactive of oirs 182A/B to grey. GUI 2037 (A) can also update ?uid lines 2029 on a graphical display. In some con?gurations, ?ow diagram lines can fall into categories such as, but not limited to, line active, line frozen, and line inactive. These lines can, for e, be assigned colors to guish them from each other in a graphical display.
Controller 2047 (A) can begin determining how to direct GUI 2037 (A) to update the cal display by determining, through queries to CANbus 2043 (B), the states of s features on the ?ow diagram. Flow diagram lines can be updated based at least on the lines from valves 216A—Z, 218A—S ( to end items, for example, but not limited to, reservoir l82A/B, drain 226, and DiRO water 192. Lines between two of valves , 218A- S (, and from valves 216A-Z, 218A-S ( to pumps 202, 204, 206, 208, 210, 212, 214 ( can also be constructed. Active lines from pumps 202, 204, 206, 208, 210, 212, 214 ( to valves 216A-Z, 218A-S (, frozen lines from valves 216A-Z, 218A-S ( to pumps 202, 204, 206, 208, 210, 212, 214 (, and lines that have changed since the last update can further be constructed.
Referring now primarily to H, in ?ow diagram 4224C, water 192 can be drawn into ?ow path 3253A by inlet pump 3227, traverse open valve 3227A (among others), and follow ?uid path 3253A to reservoir 182A. At the same time, solution 190A can be drawn into solution pump 3225, and follow fluid path 3253A to join water 192 in reservoir 182A. Fluid from reservoir 182B can be drawn into ?uid path 3225C by perfuse pump 3226 to eventually end up in ?uid path 3253B and within enclosure 100, for example perfusing a ary artery. Controller 2047 (B) can stop g from reservoirs 182A/B (F) if the level of ?uid in reservoirs 182A/B (F) is below a threshold. Controller 2047 (B) can also manage reservoir low conditions and frozen of pumps 202, 204, 206, 208, 210, 212, 214 (. Controller 2047 (B) can test and swap reservoirs l82A/B (F). Controller 2047 (B) can begin by updating substate 3053 (B) when recipe 2047A (A) is ready to proceed unless, for example, system 2048B GIG. 31B) is in pause state. Controller 2047 can log occurrences of when system 2048B (B) ?nds itself in substate 3053 (B). Controller 2047 (B) can maintain data structures that can include appropriate state-substate and state-state transitions, as well as appropriate state-mode and substate-mode relationships. To proceed with testing and swapping reservoirs 182A/B (FIG 31F), ifa single reservoir 182A or 182B (F) is being used, if mixing is not running, and if the level of a current ?lling reservoir 182A or 182B (F) is empty, then controller 2047 (B) can con?gure reservoir-in valves and mixing to be running to restart mixing to a single of reservoirs 182A/B (F). ller 2047 (B) can test and swap reservoirs 182A/B (F) and restart mixing if reservoir 182A or 182B (F) is below thresholds, if system 2048B (B) is running and using a ?rst of reservoirs 182A/B (F) while ?lling a second of reservoirs 182A/B (F), and if mixing is not disabled. In some con?gurations, controller 2047 (B) may not test and swap reservoirs 182A/B (F) and restart mixing if reservoirs 182A/B (F) are below thresholds, if reservoir 182A/B (F) that is tly being used is not empty, or if reservoir 182A or 182B (F) that is currently ?lling and reservoir 182A or 182B (F) that is currently being used are the same, if mixing is disabled, and if the step of recipe 2047A (A) requires a bolus. When mixing is enabled, and when the level of reservoir 182A or 182B (F) that is currently being used is low, and when mixing is not running, controller 2047 (B) can swap reservoirs 182A/B (F) and enable mixing. For this situation, controller 2047 (B) can verify that system 2048B (B) is in normal mode. Normal mode is when system 2048B (B) is using liquid from one reservoir 182A or 182B (F), ?ling another reservoir 182A or 182B (F), and mixing is not active. If mixing is not active, controller 2047 (B) can swap dual reservoir use from ports, con?gure reservoir-in valves and mixing, for example, when system 2048B (B) is running, start mixing to reservoir 182A/B (F) (dual reservoirs), and exit when mixing is not running and a swap of reservoirs 182A/B (FIG‘ 31F) has been con?gured. If mixing is active, controller 2047 may not complete the swap of reservoirs 182A/B (FIG‘ 31F).
Referring again primarily to H, when ng dual reservoir use from ports, controller 2047 (B) can set output valves of reservoir 182A or 182B (F), and can swap reservoir 182A or 182B (F) that is tly being used with reservoir 182B or 182A (F) that is currently , which can modify mixing when con?guring reservoir-in valves and mixing. In some con?gurations, controller 2047 (B) may not, for e, change reservoir—in valves or oir-out valves at this time, nor may controller 2047 start or stop the mixing pumps. In some con?gurations, ller 2047 (B) may not swap dual reservoir 182A/B (F) use if mixing is running. In some con?gurations, if no reservoirs 182A/B (F) are active (this can occur on initial ?lling of reservoirs 182A/B (F) before starting active processing), controller 2047 (B) may not swap reservoirs 182A/B (F). Controller 2047 can (1) swap reservoir 182A or 182B (F), that is being used, with reservoir 182A or 182B (F) that is being ?lled, (2) set substates 3053 (B) accordingly, (3) save the last states of reservoir-out valves, (4) swap the states of reservoir—out valves, (5) set the valves to the updated swapped states, and (6) set expected valve states to match the change.
Referring now to 1, in ?ow diagram 4224D, water 192 can be drawn into ?ow path 3253A by inlet pump 3227, se open valve 3227A (among others), and follow ?uid path 3225A to reservoir 182B. In ?ow diagram 4224D, solution 190A is not being drawn by solution pump 3225, and, at this snapshot, no solution is joining water 192 in oir 182B. Fluid from reservoir 182A can be drawn into ?uid path 3225B by perfuse pump 3226 to eventually end up in ?uid path 3253B and within enclosure 100, for example perfusing a pulmonary artery. GUI 2037 (A) can display a ?ow diagram and pump stic valve numbers 3231 (G) and pressures, which can be hidden. GUI 2037 (A) can display ?ow rates and a ?ow rate ?lter changed indication when pre-selected thresholds have been met.
Referring again ily to , the ?uid pumped h system 2100 may be drawn from a number of sources. In some con?gurations, ?rst ?uid source 2012 and second ?uid source 2015 can provide ?uid to ?uid circuit 2029. Fluid sources 2012, 2015 may be any of a variety of ?uid sources such as any of those described in Table I. Fluid s 2012, 2015 may be user ed to suit the needs of a speci?c procedure performed by system 2100. One or more of ?uid sources 2012, 2015 may be passed through deaerator 2013 before entering the rest of ?uid t 2021. In some con?gurations, ?uid sources 2012, 2015, may pass through one or more ?lter (e.g. 230, 234 () or regulator (e.g. 232 () before reaching the rest of ?uid circuit 2021. Filters 220, 234 ( and regulator 232 ( may be included alone or in addition to deaerator 2013. In some con?gurations, ?ltered water can enter ?uid circuit 2029 through deaerator 2013 and can be mixed, in ?uid t 2029, with concentrates to, for example, dilute concentrates to a lected or dynamic concentration appropriate for a procedure.
Continuing to refer to , power supply 2017 may be included to provide riate power to various components of the system 2100. Power supply 2017 may, for example, supply power at multiple voltages as suitable for different components of system 2100 (e. g. 24V, 12V, etc). Power supply 2017 in some con?gurations can supply power to deaerator 2013, pressure source 2011, and valve module 2019. Enclosure 100 can reside in container 174. In some con?gurations, container 174 can be "x18", though container 174 dimensions may vary. Fluid circuit 2029 can be in ?uidic communication with ical specimen 162 ( within enclosure 100 through at least one ?uid path 2021 including, but not limited to, enclosure inlet and outlet paths, and en—speci?c paths. If biological specimen 162 ( is a lung, for example, the en—speci?c paths may include a path n the ?uid circuit and the trachea, the pulmonary artery, and the pulmonary vein.
Referring now to , ?uid handling set 280 can provide a ?uid circuit similar to that of Fluid handling set 280 can e, but is not limited to including, a number of ?uid handling cassettes 282A, 282B, 282C. Each ?uid handling cassette 282A, 282B, 282C may include pumps, incoming and outgoing ports, , and ?uid paths between valves and pumps allowing the ?uid circuit to be relatively simple and compact.
Pumping and directing of ?uid through the ?uid handling cassette 282A, 282B, 282C may be driven, e. g., pneumatically as described in, for example, US. Patent 5,350,357, ?led March, 3, 1993, and entitled PERITONEAL DIALYSIS SYSTEMS ING A LIQUID DISTRIBUTION AND PUMPING CASSETTE THAT EMULATES GRAVITY FLOW, ey Docket Number 1062/ 147, which is hereby incorporated by reference herein in its entirety or as bed in US. Patent Application Serial Number 11/787,212, patent # 8,292,594, ?led April 13, 2007, issued October 23, 2012, entitled "Fluid Pumping Systems, Devices and Methods,"(E78) incorporated herein by reference in its entirety. In some con?gurations, ?uid handling set 280 can include storage reservoirs 182A, 182B and enclosure 100. Any le enclosure 100 may be used such as, but not limited to, any of those described above with reference to FIGS. 4-20. Fluid handling set 280 may be disposable for single use to, for example, streamline sterilization and/or cleaning of ?uid handling set 280.
Continuing to refer primarily to , ?rst cassette 282A may be in ?uid communication with a number of ?uid sources (such as any of those shown in Table I) via a number of attached ?uid lines 284, 292A, 292B. For example, ?rst cassette 282A can draw ?uid from ?rst line 284. First cassette 282A may also draw ?uid from a source connected to any of solution ports 290 and source lines 292A, 292B of ?rst cassette 282A. In some con?gurations, any or all of solution ports 290 may be connected to a source line. In some con?gurations, one or more port may be d or sealed and not used. In some con?gurations, one or more solution port 290 may include spike port 320 () for attachment of a vial or other source. In some con?gurations, a vial of source fluid may, for example, be spiked directly onto solution port 290 and source lines 292A, 292B may not be necessary. Solution ports 290 may also e other ?ttings such as luer locks or similar ?ttings to which source lines 292A, 292B may be attached. In some con?gurations, solution port 290 may be replaced by vent port 322 () which may allow pressure build up in a source in communication with the solution ports 290 to be ed.
Continuing still further to refer to , ?rst cassette 282A may draw in ?uid via the solution ports 290 and ?rst line 284. This ?uid may then be expelled from cassette 282A through reservoir inlet lines 286, 288 to ?uid reservoirs 182A, 182B. In some con?gurations, ?uid may be drawn in from select sources in predetermined ratios to create a ?uid mixture. The mixture may, in some rations, be created within ?rst cassette 282A or may be created by g the constituent ?uids of the mixture to ?uid reservoirs 182A, 182B and allowing the constituent ?uids to mix within storage reservoirs 182A, 182B. A ?uid mixture may, for example, be an admixture "cocktail" of the contents of a number of different sources which are in communication with ?rst cassette 282A. Additionally, a ?uid mixture may be created via ?rst te 282A by drawing in ?uid from a concentrated ?uid source as well a diluent source. Again, mixing may occur within ?rst cassette 282A or after pumping of these ?uids to ?uid reservoirs 182A, 182B. To achieve a desired tration of the concentrate in the diluted mixture, ?uid may be pumped from the concentrate source and diluent source in a predetermined ratio.
Continuing to refer to , in some con?gurations, ?rst line 284 may place ?rst cassette 282A in ?uid communication with a diluent source such as a water source (e. g. reverse osmosis, deionized, or distilled . Solution ports 290 may be connected to concentrates or additional diluent s via a vial spike or source lines 292A, 292B. Any of ed ?uid lines 284, 292A, 292B may include ?lter 234 attached to line 284 to ?lter incoming ?uid. Filter 234 can be, but is not d to being, a .2um ?lter. Incoming ?uid may also be subjected to multiple ?lters 220, 234 ( or redundant ?ltration, deaeration in deaerator 230 (, and/or subjected regulator 232 ( which may ensure ?uid is at a desired pressure. Though these components may be included within ?uid handling set 280 in some con?gurations, these components may be included in partitioned portion 222 ( to which ?uid handling set 280 connects. Any of attached ?uid lines 284, 292A, 292B may also include ?uid accumulator 236. In some con?gurations, accumulator 236 can be attached to ?rst line 284. Accumulator 236 may be any suitable type of accumulator 23 6. Accumulator 236 can be, but is not limited to being, sized according to various speci?cations of ?rst cassette 282A such as maximum estimated ?uid throughput, pump chamber volume, etc. In some con?gurations, accumulator 236 can be sized to accommodate between 25-100m1 (eg. 50ml) of ?uid. ing now ily to , in some con?gurations, lator 236 can include, but is not limited to including, rigid housing 450 with a displaceable ?exible membrane or barrier 452 therein. Flexible membrane 452 may be constructed of an elastomeric material, ?exible plastic, or other substantially impermeable barrier. Rigid housing 450 may be constmcted of a rigid c. Flexible membrane 452 may de?ne two variable volume chambers 454A, 454B within rigid housing 450. The volume of each variable volume chamber 454A, 454B may change as ?exible membrane 452 ces with one volume increasing and the other decreasing in direct proportion. In some rations, ?rst le volume chamber 454A may be a wet chamber in communication with ?rst line 284 via ?rst accumulator port 456.
Flexible membrane 452 may create a seal between ?rst le volume chamber 454A and second variable volume chamber 454B. Second le volume chamber 454B may be in communication with the atmosphere via vent port 458. Fluid in ?rst line 284 may be at a pressure higher than atmospheric pressure. In the event that ?uid throughput of ?rst cassette 282A () is lower than a ?uid supply rate to ?rst line 284, ?rst variable volume r 454A may increase in volume and air may be displaced out of second variable volume r 454B via vent port 458. Thus accumulator 236 may accumulate a reserve of ?uid. This reserve of ?uid may help ensure that there is extra ?uid ble for ?rst cassette 282A if ?rst cassette 282A is drawing ?uid from ?rst line 284 at a rapid rate (e. g. a rate higher than the supply rate). id="p-242" id="p-242"
id="p-242"
[00242] Referring again to , storage reservoirs 182A, B may be included in ?uid handling set 280. In some con?gurations, two storage reservoirs 182A, B are included though the number of e reservoirs 182A, B may differ. Storage reservoirs 182A, B may include one or more port to which a ?uid line may be connected. Each of storage reservoirs 182A, B may be in ?uid communication with each cassette 282A, 282B, 282C of ?uid handling set 280. Storage reservoirs 182A, B may, for example, receive ?uid from ?rst cassette 282A respectively via reservoir inlet lines 286, 288. In some con?gurations, cassette 282A may also be capable of drawing ?uid from storage reservoirs 182A, B via lines 286, 288. Storage reservoir 182A may be in communication with cassettes 282B, 282C respectively via reservoir outlet lines 302B, 302C. Reservoir outlet lines 302B, 302C may split from common line 302A at a Y—site in some con?gurations. e reservoir 182B may be in communication with second cassettes 282B, 282C respectively via reservoir outlet lines 304B, 304C. These lines 304B, 304C may also split from a common line 304A at a Y-site in some con?gurations. In some rations, second tes 282B, C may each have a dedicated storage oir. In some con?gurations, storage reservoir 182A can feed second cassette 282B, and storage reservoir 182B can feed second cassette 282C. In some con?gurations, the storage reservoirs 182A, B may be shared between cassettes 282B, C and each cassette 282B, C may draw from each storage reservoir 182A, B. Any con?guration that can accommodate providing ?uid to second cassettes 282B, C can be included within the scope of the present teachings.
Continuing to refer to , storage reservoirs 182A, B can include ports for air vent lines 298A, B, over?ow lines 294A, B, and level lines 296A, B. Air vent lines 298A, B may allow air to escape or enter storage reservoirs 182A, B as the level of ?uid in storage reservoirs 182A, B changes. This may help ensure no pressure build up occurs within a storage reservoirs 182A, B. Air vent lines 298A, B can optionally include ?lters 300A, B.
Filters 300A, B may be a 0.2 micron ?lter. w lines 294A, B may be in ?uid communication with an over?ow reservoir (not shown) which may hold excess ?uid in the event that storage reservoirs 182A, B are over—?lled. Level lines 296A, B may be in communication with a sensor which is red to e a determination of the ?uid level within storage reservoirs 182A, B. Level lines 296A, B will be described elsewhere in the speci?cation.
Continuing to refer primaiily to , second tes 282B, C can be, for example, mirror images of each other. In some con?gurations, second cassettes 282B, C may be identical and the arrangement of ?uid lines may differ. In some rations, second cassettes 282B, C may differ from one r. Each second cassette 282B, C may, for example, each be lized or optimized to perform a speci?c task. Second cassettes 282B, C may be in communication with a number of ?uid lines to/from which ?uid may be drawn or pumped.
Second cassettes 282B, C may be in communication with one or more storage reservoirs 182A, B. Second cassettes 282B, C may each be in communication with loop lines 308B, 308C respectively. In some con?gurations, only one or neither of second cassettes 282B, C may be in communication with loop lines 308B, 308C. Loop lines 308B, 308C will be bed elsewhere in the speci?cation. Second tes 282B, 282C may be in communication with lines 306B, 306C of waste line 306A which may lead to waste reservoir 180 (. Air bubbles and used, excess, spent, or otherwise unacceptable ?uid, for e, may be pumped by second cassettes 282B, 282C to waste line 306A, ly, but not limited to, for disposal.
Continuing to still further refer to , second tes 282B, 282C may also be in communication with a number of ?uid buses 310. Fluid buses 310 may be attached to a number of ?uid lines extending to one or more enclosure 100. In some con?gurations, ?rst ?uid line 319, second ?uid line 311, and a number of specimen ?uid lines 313, 315, 317 can be ted to at least one of ?uid buses 310. Fluid may be pumped into or drawn from ?uid lines 311, 313, 315, 317, 319 through the ?uid buses 310 to transfer ?uid to/from enclosure 100 or biological specimen 162 ( within enclosure 100. In some con?gurations, such as those where second cassettes 282A, B are not mirror images, but identical, shared ?uid buses 310 may not be included. Instead ?uid lines 311, 313, 315, 317, 319 may include branches that can be associated with each second cassette 282A, 282B.The branches may, for example, resemble drain line 306A which can include drain lines 302B, 306C.
In some con?gurations, multiple of each of ?uid lines 311, 313, 315, 317, 319 may be included in ?uid handling set 280 and each second cassette 282B, 282C may be ated with its own dedicated ?uid lines 311, 313, 315, 317, 319. In con?gurations with a plurality of ures 100 included in ?uid handling set 280, each second cassette 282B, C may be associated with ?uid lines 311, 313, 315, 317, 319 from one of enclosures 100. Additional cassettes 282A, 282B, 282C and/or other types of cassettes may be included in ?uid handling set 280.
Continuing to still further refer primarily to , operationally, ?uid handling set 280 can circulate speci?c ?uids h biological specimen(s) 162 ( and enclosure 100 according to an automatic process, a manual process, or a combination of both. A recipe ing, for example, but not limited to, ingredients and valve positions as a function of, for example, time, can be constructed that can facilitate an automatic process which can be dden manually. First cassette 282A can be ed to provide suf?cient ?uid to storage oirs 182A, B, and second cassettes 282B, 282C can allow continuous ?ow into enclosure 100 without risking the integrity of enclosure 100. For example, second cassette 282B can be delivering ?uid to enclosure 100 via ?rst ?uid line 311 while second cassette 282C can be draining enclosure 100 via second ?uid line 319. Fluid drained from enclosure 100 may be pumped to waste line 306A or, if recirculation is desired may be pumped back to enclosure 100. uing to refer to , if it is desired to pump air into enclosure 100 or to biological specimen(s) 162 ( within ure 100, storage reservoirs 182A, B, for example, can be emptied of contents, leaving air behind. Second cassettes 282B, 282C can then draw air from storage reservoirs 182A, B and pump the air through ?uid lines 313, 315, 317 to en(s) 162 (. In some con?gurations, second cassettes 282B, 282C may include vent port 322 () which may be used to draw in air for pumping. Fluid handling set 280 can be ed partially or entirely manually through a graphical user interface 2037 () in which valves that control ?uid ?ow can be toggled individually or in prede?ned groups to move ?uid hout ?uid handling set 280 and/or biological specimen 162 ( in ure 100. In some con?gurations, ?uid handling set 280 may be partially manually operated based on information provided to graphical user interface 2037 (). The commands may be associated with prede?ned control ons which can accomplish a desired pumping task. For example, a manually input command may be in the form of "pump ‘X’ volume of ?uid from ‘A’ to ‘B’ at rate ‘Y’ using te ‘Z’" where the variable parameters may be manually de?ned.
Referring now primarily to , ?rst cassette 282A may be operated to deliver desired ?uids to storage reservoirs 182A, B () and may function as a mixing cassette to create desired ?uid mixtures. First cassette 282A may include cassette body 343.
Cassette body 343 may be a rigid member which can be, for example, but not limited to, constructed from a hard plastic or other hard material. Cassette body 343 may be manufactured in any number of le manners such as molding, machining, etc. Cassette body 343 may be, for e, but not limited to, a generally planar structure from which a number of walls 344 and perimeter wall 345 project. Walls 344, 345 may project at an angle that can be substantially perpendicular from the plane of cassette body 343. First cassette 282A can also include a number of valve seats 347 which can project away from cassette body 343, for e, similar to walls 344, 345. Each valve seat 347 may be surrounded by walls 344 which can de?ne valve well 380A. Walls 344, 345 of cassette 282A may extend proud of valve seats 347.
] Continuing to refer to , ?rst te 282A may also include cassette sheeting or membrane 346A, 346B. Cassette sheeting 346A, 346B may be generally planar pieces of material. te sheeting 346A, 346B may be, for example, but not limited to, substantially impermeable and ?exible, for example a e plastic or elastomeric material.
Cassette sheeting 346A, 346B may be attached to each side of cassette body 343 at perimeter wall 345, and can overlay walls 344 of te 282A. Cassette sheeting 346A, 346B may be positioned on ?rst cassette 282A and attached to ?rst cassette 282A e. g., by heat bonding, adhesive, ultrasonic welding or other means. Cassette ng 346A, 346B can be a e polymer ?lm made from, for example, polyvinyl chloride (PVC), that is cast, extruded or otherwise . Alternatively, the cassette sheeting 346A, 346B may be formed as a laminate of two or more layers of poly-cyclohexylene dimethylene cyclohexanedicarboxylate (PCCE) and/or ULDPE, held together, for example, by a coextrudable adhesive (CXA). Urethane may also be used. The thickness of cassette sheeting 346A, 346B may be any suitable thickness, and in some con?gurations, in the range of approximately 0.002 to 0.020 inches thick. In one con?guration, the thickness may be in the range of approximately 0.012 to 0.016 inches thick, and in one con?guration, can be approximately 0.014 inches thick. id="p-250" id="p-250"
id="p-250"
[00250] Continuing to still further refer to , when pressure is applied to each side of cassette body 343, cassette sheeting 346A, 346B may be forced against walls 344 of cassette body 343. The pressure can, for e, form ?uidically sealed chambers and pathways in ?rst cassette 282A. te sheeting 346A, 346B may be, but is not limited to being, prevented from being forced against each of valve seats 347 because walls 344 may be, for example, proud of valve seats 347. Positive re (pressure may be exerted mechanically or by a control ?uid pneumatically, hydraulically, etc.) applied to cassette ng 346A, 346B over valve seat 347 may displace cassette sheeting 346A, B into contact with valve seat 347.
Negative pressure may displace cassette sheeting 346A, B away from valve seat 347. One or more piece of cassette sheeting 346A, 346B may optionally include one or more preformed region 348A, 348B, 348C. Preformed regions 348A, 348B, 348C may be, but are not limited to being, depression-like features in cassette sheeting 346A, 346B which can generally conform to the contours of various portions of ?rst cassette 282A. Preformed regions 348A, 348B, 348C may be added to cassette sheeting 346A, 346B during manufacture. te ng 346A, 346B may be, for example, generally formed as a ?at member and preformed regions 348A, 348B, 348C may later be formed. In some con?gurations, preformed regions 348A, 348B, 348C can correspond to pump chambers 332, 334, 336 of ?rst cassette 282A. The dome- like preformed shapes can, for example, conform to pump chamber 332, 334, 336 depressions of ?rst te 282A. The ike shape of preformed portions 348A, 348B, 348C may be constructed, for example, by heating and forming cassette sheeting 346A, 346B over a vacuum form mold. The vacuum form mold can press a sheet of cassette sheeting 346A, 346B against ?rst cassette 282A and bond them together.
Continuing to refer 'ly to , when ?rst cassette 282A is assembled, each pump chamber 332, 334, 336 can be, for example, de?ned in part by cassette sheeting 346A, B. Each of pump chambers 332, 334, 336 can, for example, be de?ned in part by walls 344 extending from cassette body 343 to create depressions in pump chambers 332, 334, 336. Application of pressure to cassette sheeting 346A, 346B over pump chambers 332, 334, 336 may cause the volume of pump chambers 332, 334, 336 to vary. Negative pressure can draw cassette sheeting 346A, 346B away from te body 343 and can increase the volume of pump chamber 332, 334, 336. If, in communication with a ?uid source such as, for example, but not limited to, source 190 ( and/or storage reservoirs 182 (, ?uid may be drawn into one or more of pump chambers 332, 334, 336 when negative pressure is applied, ing a ?ll pump stroke. Positive pressure can force cassette sheeting 346A, 346B toward cassette body 343 and decrease the volume of one or more of pump chambers 332, 334, 336.
When one or more of pump chambers 332, 334, 336 contains ?uid, the application of ve pressure may cause the ?uid to be expelled from one or more of pump chambers 332, 334, 336, executing a deliver pump stroke.
As with cassette sheeting 346A, 346B over valve seat 347, pressure may be applied in any of a y of ways (eg. mechanically or by a l ?uid pneumatically, hydraulically, etc). In con?gurations where cassette sheeting 346A, 346B includes preformed regions 348A, 348B, 348C, preformed regions 348A, 348B, 348C may ce to conduct pumping action without requiring signi?cant (or any) stretching of cassette sheeting 346A, 346B, even when a region of cassette sheeting 346A, 346B is at a maximum excursion point (e.g. when an associated pump chamber 332, 334, 336 is at minimum or maximum volume).
] Continuing to refer to , in some rations, cassette sheeting 346A, 346B (also referred to as ?exible sheeting) may also be bonded to walls 344 of ?rst cassette 282A. For example, cassette sheeting 346A, B may be bonded to walls 344 that form s pathways or buses within ?rst cassette 282A and can cover at least one pump chamber 332, 334, 336 (). At least one piece of cassette sheeting 346A, 346B may be formed of a rigid sheet of material that is bonded or otherwise made integral with ?rst cassette 282A. Thus, at least one piece of cassette sheeting 346A, 346B need not necessarily be, or include, a e member. Similarly, cassette sheeting 346A, 346B need not be ?exible over its entire surface, but instead may include one or more ?exible portions to permit pump and/or valve operation, and one or more rigid portions, e.g., to close ?uid buses of ?rst cassette 282A. In some con?gurations, ?rst cassette 282A can include ?uid buses or pathways that can be otherwise sealed or fully enclosed within ?rst cassette 282A without cassette sheeting 346A, 346B.
] Referring now primarily to FIGS. 35, 36, and 38, ?rst cassette 282A can include, but is not limited to ing, ?rst side 283 () and second side 285 ().
First cassette 282A may also include one or more pump chamber, for example, ?rst pump chamber 332, second pump chamber 334, and solution pump chamber 336. Each of pump chambers 332, 334, 336 may be a variable volume chamber which may be de?ned in part by cassette sheeting 346A, 346B () which may act as a displaceable diaphragm. Pressure applied to one or more pump chambers 332, 334, 336 may cause ?uid to be drawn into or forced out of one or more pump rs 332, 334, 336. First cassette 282A may e, but is not limited to including a number of ?uid valves 13.1, 7.1—7.4, 10.1, 10.4, 4, 12.4, 11.4, 9.1, 13.2, 12.1, 11.1 (eg. volcano valves) which may be independently opened and closed to make and break ?uid communication with ?uid pathways 324, 326, 328A, 328B, 330A, 330B, 338A, 340, 342 () on second side 285 () of ?rst cassette 282A. Each of ?uid valves 13.1, 7.1-7.4, 10.1, 10.4, 8.1-8.4,12.4,11.4, 9.1,13.2,12.1,1111in ?rst cassette 282A may be ated with valve seats 347 (). Cassette sheeting 346A, 346B () may be forced against or pulled away from valve seats 347 () associated with valves 13.1, 7.1- 7.4, 10.1, 10.4, 4, 12.4, 11.4, 9.1, 13.2, 12.1, 11.1 to respectively close or open valves 13.1, 7.1-7.4,10.1,10.4, 8.1-8.4,12.4,11.4, 9.1,13.2,12.1,11.1. Valves 13.1, 7.1-7.4, 10.1, 10.4, 4, 12.4, 11.4, 9.1, 13.2, 12.1, 11.1 can be opened and closed to direct ?uid ?ow when ?uid is pumped via one or more of pump chambers 332, 334, 336. Fluid in valve well 380A () may, for example, ?ow through valve 12.1 to a ?ow path on the opposing side of the cassette 282A if the sheeting 346A, 346B () is not pressed against valve seat 347 () of valve 121 Continuing to refer primarily to FIGS. 35, 36, and 38, cassette sheeting 346A, 346B () may also serve to create a ?uid tight seal for ?uid pathways 324, 326, 328A, 328B, 330A, 3303, 33 8A, 340, 342 () such that ?uid in ?uid pathways 324, 326, 328A, 328B, 330A, 330B, 338A, 340, 342 () can be con?ned within each of ?uid pathways 324, 326, 328A, 328B, 330A, 3303, 338A, 340, 342 (). First cassette 282A may also include a number of ?uid ports 290, 322, 284A, 286A, 288A, 320. Each of ports 290, 322, 284A, 286A, 288A, 320 may be ted to ?uid lines, or conduits leading to ?uid sources 190 ( or reservoirs 182 (. ion of pump chambers 332, 334, 336, and valves 13.1, 7.1, 7.2, 7.3, 7.4, 8.2, 10.1, 10.4, 8.1, 12.4, 11.4, 8.3, 9.1, 13.2, 12.1, 11.1, 8.4 may allow ?uid to be pumped into or out of ?rst te 282A through one or more of ports 290, 322, 284A, 286A, 288A, 320. Closing all ofvalves 13.1, 7.1, 7.2, 7.3, 7.4, 8.2, 10.1, 10.4, 8.1, 12.4, 11.4, 8.3, 9.1, 13.2, 12.1, 11.1, 8.4 which are not associated with a desired of ?uid pathways 324, 326, 328A, 328B, 330A, 330B, 338A, 340, 342 () to one or more of ports 290, 322, 284A, 286A, 288A, 320 may allow one or more pump rs 332, 334, 336 to be in exclusive communication with the desired ports 290, 322, 284A, 286A, 288A, 320. Depending on how valves 13.1, 7.1, 7.2, 7.3, 74, 8.2, 10.1, 10.4, 8.1, 12.4, 114, 8.3, 9.1, 132, 12.1, 11.1, 8.4 are ed in relation to the actuation of pump chambers 332, 334, 336, ?uid may be pumped either in a ?rst direction, or in a second direction. That is, one or more of pump chambers 332, 334, 336 may transfer ?uid into and out of one or more ports 290, 322, 284A, 286A, 288A, 320 of ?rst cassette 282A such that one or more ports 290, 322, 284A, 286A, 288A, 320 may behave as inlets and outlets.
Referring now to , in some con?gurations, solution ports 290 may be attached to solution lines 292A-D providing ?uid from various sources 190A-F. Sources 190A-F may differ and a non limiting number of example sources 190A-F are shown in .
In some con?gurations, manifold 191 for, for example, sources 190A-C may be attached to solution port 290 by solution line 292A which can be used by manifold 191 as a common inlet to ?rst cassette 282A. Each type of source l9OA—C on manifold 191 may be different or, in some con?gurations, at least two sources l90A-C on manifold 191 may be the same. In some con?gurations, solution line 292B may be connected to solution bag l90D. Any size solution bag 190D may be used to provide the source ?uid. In some con?gurations, solution line 292C may be in communication with reservoir l90E which can be, for example, a drum or other bulk size container. Solution line 292D may be placed in communication with ?ask l90F or other laboratory vessel. Flask l9OF may be desirable in scenarios where the incoming ?uid is manually produced or produced on site. Other source l90A-F types may also be used.
Continuing to refer to , in some rations, ?rst cassette 282A may include one or more spike(s) or spike port(s) 320. Spike port 320 can include, but is not limited to including, a needle or hollow spike that can pierce a seal or septum of source vial 394 or other source reservoir. Spike port 320 may be formed from, for example, but not limited to, c, or a metal such as stainless steel. In some con?gurations, spike port 320 may be made from a sterilizable material which may be able to withstand suf?ciently high temperatures and/or chemical/radiation exposure related to a sterilization process. Spike port 320 may be used to spike source vial 394 such that ?uid may be drawn through spike port 320 into ?rst cassette 282A. In some rations, spike 320 may be omitted. For example, spike port 320 may be replaced by solution port 290. Some con?gurations may include additional spike ports 320 which may be in addition to or substituted for one or more of solution ports 290. id="p-258" id="p-258"
id="p-258"
[00258] Continuing to refer to , in some rations, ?rst te 282A may include vent port 322. Vent port 322 can allow pressure build up in sources l9OA-F or source vials 394 to be relieved. Source l9OA-F and source vial 394 may be placed in ication with vent port 322 to equalize the pressure of source l90A-F and source vial 394 with ambient pressure as ?uid is drawn into ?rst cassette 282A. Vent port 322 may also be used to pump or purge undesired ?uid such as air out of ?rst cassette 282A. Vent port 322 may include a ?lter, such as a 0.2 micron ?lter. Vent port 322 may include a hydrophobic ?lter. In some con?gurations, air may be introduced from vent port 322 into ?rst cassette 282A through operation of at least one of pump chambers 332, 334, 336. The air may, for e, be pumped throughout ?rst cassette 282A to purge ?rst cassette 282A of a ?rst ?uid before re- priming ?rst te 282A with another ?uid. In some con?gurations, vent port 322 may be omitted. For example, vent port 322 may be ed by solution port 290. Some rations may include onal vent port(s) 322 which may be in addition to or substituted for one or more of solution ports 290.
] Continuing to refer primarily to , among the ?uid pathways of ?rst cassette 282A may be on bus 324. Solution bus 324 may be a common bus for solution drawn into ?rst cassette 282A through solution ports 290 and spike ports 320. Valves 7.4, 7.2, 7.1, 8.2, 131 may be opened and closed to make and break ?uid communication between solution bus 324 and one or more of ports 290, 320, 322. For example, opening valve 7.2 while closing valves 7.4, 7.1, 8.2, 13.1 could place spike port 320 in communication with solution bus 324 while isolating solution ports 290 and vent port 322 from solution bus 324. Fluid may then be transferred between solution bus 324 and spike port 320.
Additional ports including, though not limited to, ?rst line port 284A, ?rst reservoir port 286A, and second reservoir port 286A may be included in ?rst cassette 282A.
These ports may be connected to various ?uid lines leading to fluid sources 190 ( and reservoirs 182 (. For example, ?rst line port 284A may be ted to ?rst line 284 g to a diluent source in some con?gurations. First and second reservoir port 286A, 288A may be respectively connected to ?rst reservoir line 286 and second reservoir line 288 g to storage reservoirs 182A, 182B () of ?uid handling set 280 (). uing to refer primarily to , among the ?uid pathways of ?rst cassette 282A may be pump chamber bus 326, ?rst reservoir inlet path 340 and second reservoir inlet path 342. Pump r bus 326 may allow ?uid to be transferred between ?rst cassette 282A and ?rst line 284. The ?uid may, for example, be a diluent such as puri?ed water in some con?gurations. First reservoir inlet path 340 and second oir inlet path 342 may allow ?uid to be transferred between ?rst cassette 282A and ?rst and second reservoir lines 286, 288.
Central bus 338A h it may be included anywhere on the cassette 282A and not necessarily near the cassette 282A center) may also be included among the ?ow pathways. First cassette 282A may include ?rst pump chamber 332, second pump chamber 334, and solution pump chamber 336. In some con?gurations, ?rst cassette 282A may be con?gured such that any of pump chambers 332, 334, 336 may be placed in ?uid communication with any of ports 290, 320, 284A, 286A, 288A. While in ?uid communication with a desired of ports 290, 320, 284A, 286A, 288A, negative pressure may be applied to sheeting 346A () over one or more pump chambers 332, 334, 336 to ?ll one or more pump chambers 332, 334, 336 with ?uid from ?uid source 190 ( or reservoirs 182 ( connected to one or more of ports 290, 320, 284A, 286A, 288A. Positive pressure may be applied to expel ?uid within one or more of pump chambers 332, 334, 336 to one or more ?uid lines connected to one or more of ports 290, 320, 284A, 286A, 288A. Each of pump chambers 332, 334, 336 may be placed in communication with one another. Thus, the ?ow of ?uid from any of ports 290, 320, 284A, 286A, 288A h ?rst cassette 282A may be controlled by any of pump chambers 332, 334, 336. Only one of pump chambers 332, 334, 336 need be operable to draw ?uid into itself. Other of pump chambers 332, 334, 336 may be left inoperable and closed off to ?ow by g the appropriate valves. id="p-262" id="p-262"
id="p-262"
[00262] uing to still further refer to , with respect to ?rst pump chamber 332, communication with ?rst line port 284A may be established by opening valve 111 creating a ?uid pathway from pump chamber bus 326 to ?rst pump chamber inlet/outlet path 328A and into ?rst pump chamber 332 via pump chamber inlet/outlet 329A. Communication with solution line bus 324 may be ished by opening valves 8.1 and 114. Opening valves 8.1 and 11.4 may generate a ?uid pathway from solution bus 324 to l bus 338A and from central bus 338A to ?rst pump chamber inlet/outlet path 328B. First pump chamber inlet/outlet path 328B is in communication with ?rst pump r 332 via pump chamber inlet/outlet 329B. Communication with ?rst reservoir port 286A may be ished by opening valves 8.3 and 11.4. Opening valves 83 and 11.4 may te a ?uid pathway from ?rst reservoir path 340 to l bus 33 8A and from central bus 338A to ?rst pump chamber inlet/outlet path 328B. ication with ?rst pump chamber inlet/outlet path 328B may be established by opening valves 9.1, 8.3, and 11.4. Opening valves 9.1, 8.3, and 114 may generate a ?uid pathway from second reservoir path 342 to ?rst reservoir path 340 onto central bus 338A and into pump chamber 332 through ?rst pump chamber inlet/outlet path 328B. id="p-263" id="p-263"
id="p-263"
[00263] Continuing to refer to , with respect to second pump chamber 334, communication with ?rst line port 284A may be established by opening valve 12.1 creating a ?uid pathway from pump chamber bus 326 to second pump chamber inlet/outlet path 330A and into second pump chamber 334 via pump chamber inlet/outlet 327A. Communication with solution line bus 324 may be established by opening valve 8.1 and 124. Opening valve 8.1 and 12.4 may generate a ?uid pathway from on bus 324 to central bus 33 8A and from central bus 338A to second pump chamber inlet/outlet path 330B. Second pump chamber inlet/outlet path 330B may be in communication with pump chamber inlet/outlet 327B. Communication with ?rst reservoir port 286A may be ished by opening valves 8.3 and 12.4. Opening valves 83 and 124 may te a ?uid pathway from ?rst reservoir path 340 to central bus 338A and from the central bus 338A to second pump chamber inlet/outlet path 330B. ication with second reservoir port 328A may be established by opening valves 9.1, 8.3, and 124. Opening valves 9.1, 8.3, and 12.4 may generate a ?uid y from second reservoir path 342 to ?rst reservoir path 340 onto central bus 338A and into second pump r 334 through second pump chamber inlet/outlet path 330B.
Continuing to refer to , with respect to solution pump chamber 336, communication with solution line bus 324 may be established by opening valve 10.1 establishing a pathway from solution bus 324 to solution pump chamber outlet path 337A.
Solution pump chamber inlet/outlet path 337A is in communication with solution pump chamber 336 via solution pump chamber inlet outlet 335A. Communication with ?rst line port 284A may be established by opening valves 13.2 and 101. Opening valves 13.2 and 10.1 may create a ?uid pathway from pump chamber bus 326 to solution bus 324 and on to solution pump chamber inlet/outlet path 337A. Communication with ?rst oir port 286A may be established by opening valve 104. Opening valve 104 may generate a ?uid pathway from ?rst reservoir path 340 to solution pump chamber inlet/outlet path 337B. Solution pump chamber inlet/outlet path 337B is in communication with solution pump chamber 336 via solution pump chamber inlet/outlet 335B. Communication with second reservoir port 228A may be established by opening valves 9.1 and 10.4. Opening valves 9.1 and 104 may generate a ?uid pathway from second reservoir path 342 to ?rst reservoir path 340 onto solution pump r inlet/outlet path 337B.
Continuing to refer to , the ?uid pathways described herein for placing pump chambers 332, 334, 336 in communication with c ports 290, 320, 284A, 286A, 288A are merely exemplary. More than one pathway can be established by opening and closing of valves of ?rst cassette 282A to place one or more of pump rs 332, 334, 336 in communication with a desired of ports 290, 320, 284A, 286A, 288A. Multiple of pump chambers 32, 334, 336 may be placed in communication with the same of ports 290, 320, 284A, 286A, 288A at the same time. By opening valves 12.4, 11.4, 8.3, and 10.4 all of pump chambers 332, 334, 336 may, for example, be operated to deliver ?uid to ?rst oir port 286A.
In some rations, ?rst line 284 may be connected to a diluent source. Each of solution ports 290 and spike ports 320 may be connected to a variety of sources 190A-F and vial 394 which can contain a trate or number of concentrates. If the concentrate in source 190A-F and vial 394 requires reconstitution, one or more of pump rs 332, 334, 336 may be placed in ication with ?rst line port 284A and ?lled with diluent. The diluent may then be expelled from one or more of pump chambers 332, 334, 336 to source 190A—F and vial 394 through one or more of ports 290, 320 associated with source l90A-F and vial 394. In some con?gurations, one or more of pump chambers 332, 334, 336 may be operated to pump the partially reconstituted concentrate back and forth between one or more of pump chambers 332, 334, 336, and source 190A-F and vial 394. Pumping the partially reconstituted concentrate back and forth may help to facilitate reconstitution. In some con?gurations, reconstitution may be performed similar to as bed in US. Patent No. 6,726,656, ?led October 8, 2002, and entitled System For Controlling Flow Through a Line During Intravenous Drug Delivery, Attorney Docket No. D26 which is orated by reference herein in its entirety.
Still further referring primarily to , in some con?gurations, diluent may be pumped via one or more of pump chambers 332, 334 from ?rst line port 284A through ?rst cassette 282A to one or more of reservoir ports 286A, 288A. The diluent may then proceed through reservoir inlet line 286, 288 to one or more storage oirs 182A, 182B ()‘ trate fluid from a desired of sources 190A-F and vial 394 may be pumped via solution pump chamber 336 from solution bus 324 to one or more of reservoir ports 286A, 288A. The concentrate ?uid may then proceed h reservoir inlet line 286, 288 to one or more storage reservoirs 182A, 182B (). With the concentration of the concentrate in source l9OA—F, 394 known, the ratio of diluent to concentrate pumped may be altered such that the ?uid mixture delivered to one or more storage reservoirs 182A, 182B () is at a desired concentration.
In some con?gurations, the ratio of diluent to concentrate may, for example, be one full solution pump r 336 delivered for every ten full deliveries from any of pump chambers 332, 334.
If a full delivery of one of pump chambers 332, 334 is ?ve times the volume of a full delivery of solution pump chamber 336, the ratio would be 50:1. For ?ner control of the ratio, partial deliveries of any of pump chambers 332, 334, 336 may also be performed. In some rations, partial deliveries may be done by calculating the volume of ?uid transferred between one or more of pump chambers 332, 334, 336 and one or more of sources 190A-F, vial 394, and reservoir ports 286A, 288A as the pump stroke is in ss. When the desired volume of ?uid has been pumped, the stroke may be terminated. Such displaced volume accounting as a stroke is in progress may be conducted as described in US. Patent Application Serial No. 14/732,564, ?led June 5, 2015, and entitled l Treatment System and Method Using a Plurality of Fluid Lines, Attorney Docket No. Q24 which is incorporated by reference herein in its entirety. In some con?gurations, dilution may be performed within ?rst cassette 282A. Two ?uids, e. g. a diluent and a trated source ?uid may be mixed similarly to as described in US Patent No. 7,461,968, ?led October 30, 2003, and entitled System, Device, and Method for Mixing Liquids, Attorney Docket No. D71 which is incorporated by reference herein in its entirety.
Referring now cally to , ?rst te 282A can include one or more pump chambers. Each of pump chambers 332, 334, 336, may be identical or may differ from one another. For example, solution pump chamber 336 can have a different design from pump chambers 332, 334. on pump chamber 336 may be a small volume chamber, 6. g. 5— 20ml or in some con?gurations 10ml in volume when fully ?lled. Pump rs 332, 334 may or may not be of equal volume and may be larger in volume than solution pump chamber 336 when fully ?lled. In some con?gurations, pump chambers 332, 334 may be about 3.5-7 times (e. g. 5 times) larger in volume when fully ?lled than solution pump chamber 336. In some con?gurations, pump chambers 332, 334 may each be about 40-50ml (e.g. 50ml) in volume when fully ?lled.
Each of pump chambers 332, 334, 336 may be of different or identical geometry. For example, solution pump chamber 336 may have a generally circular int while pump chambers 332, 334 can be, for example, but not limited to, ovoid, elliptical, oblong, and stadium shaped. In some con?gurations, solution pump chamber 336 may be at least partially formed as a generally hemispherical or spherical cap like depression in ?rst cassette 282A. Pump chambers 332, 334 may be de?ned at least partially by ?at bottomed sions in ?rst cassette 282A. One or more of pump chambers 332, 334, 336 may include spacers 337.
For example, pump chambers 332, 334 may include spacers 337 while solution pump chamber 336 can be devoid of spacers 337. Spacers 337 may be similar to those described in US. Patent 6,302,653, ?led July 20, 1999, and entitled METHODS AND SYSTEMS FOR DETECTING THE PRESENCE OF A GAS IN A PUlVIP AND PREVENTING A GAS FROM BEING PUMPED FROM A PUMP, ey Docket No. 7001 and, US Patent Application Serial Number 13/667,696, ?led November 2, 2012, and entitled MEDICAL TREATMENT SYSTEM AND METHODS USING A PLURALITY OF FLUID LINES, Attorney Docket Number I95 both of which are incorporated herein by reference in their entireties. Spacers 337 will be described further herein.
Continuing to refer to , each pump chamber 332, 334, 336 may have re applied in a different manner (e. g. mechanically v. with a control ?uid) or with different control ?uids. In some con?gurations, pressure may be applied to pump rs 332, 334, 336 in a different manner than it is applied to sheeting over valve seats 347 ().
For example, the pressure may be applied to pump chambers 332,334, 336 with a control ?uid while ng 346A, 346B may be ically d against valve seats 347. id="p-271" id="p-271"
id="p-271"
[00271] Referring now to FIGS. 37A and 37B, cross sectional views of an example ?rst cassette 282A taken at lines 22C-22C and 22D-22D of are shown. In some con?gurations, the pump chambers 332, 334, 336 depressions may be de?ned by chamber depression faces 338.
Referring now primarily to A, spacers 337 may be omitted from at least one pump chamber 332 (), 334 (), 336 of ?rst cassette 282A. Solution pump chamber 336, for example, may be de?ned by a relatively featureless or bald depression face 338.
Referring now primarily to FIGS. 37B and 37C (which is an enlarged view of region 22E in B), depression face 338 (A) of pump chambers 332, 334 () can include spacers 337 which can project away from sion face 33 8. Spacers 337 may , for example, but not limited to, in a manner substantially dicular from depression face 338 or in a manner parallel to walls 344 (B) of ?rst cassette 282A (). Spacers 337 can be spaced, for example, but not limited to, an equal distance apart from one another. The height of s 337 may be equal or may progressively increase or decrease in size within pump chambers 332, 334, 336 (). In one con?guration, spacers 337 can be arranged in a kind of "stadium seating" arrangement such that spacers 337 can be arranged in a concentric elliptical pattern with ends of spacers 337 increasing in height from one portion of depression face 338 to another to form a semi-elliptical domed shaped region. Spacers 337 may have, for example, but not limited to, top face 379A (C) that is, for example, but not d to, ?at or sloped. Edges 378A (C) of top face 379A (C) may be beveled, rounded, or chamfered. Top face 379A (C) of each spacer 337 may serve as a contact face for cassette sheeting 346A, 346B () when cassette sheeting 346A, 346B () travels into pump chambers 332, 334 (). Spacers 337 may at least partially de?ne the shape or curvature of cassette sheeting 346A, 346B () at an excursion into pump chambers 332, 334 (). id="p-274" id="p-274"
id="p-274"
[00274] Continuing to refer primarily to FIGS. 37B and 37C, by preventing t of cassette sheeting 346A, 346B () with depression face 338, spacers 337 can provide a dead space (or trap volume or tidal volume) which can trap an undesired ?uid such as air or other gas in pump chambers 332, 334 () during g. The trap volume may aid in inhibiting undesired ?uid from being pumped out of pump chambers 332, 334 () unless desired. Also, spacers 337 can prevent cassette sheeting 346A, 346B () from sticking to depression faces 338. In addition, spacers 337 can prevent cassette sheeting 346A, 346B () from ting pump chamber inlet/outlets 329A, 329B, 327A, 327B () . Spacers 337 may also be arranged so as to allow undesired ?uid to move toward a location of pump chambers 332, 334 where it may be easily discharged to, for example, but not limited to, waste line 306A (), vent port 322 (), or other location. Discharging ?uid may be accomplished, for example, by providing ?uidic ication between spacers 337 such that ?uid may pass between spacers 337 near depression face 338. When spacers 337 are positioned in a um seating" arrangement, "aisles" or breaks 339, 341 in the elliptical n, for example, can be included. y of the ?uids may be leveraged to aid in moving ?uid toward a discharge point. For example, ?rst cassette 282A () may be used in a prescribed orientation. Aisles 339 (B), 341 and the discharge point (eg. one of ports 327A, 327B, 329A, 329B ()) may be arranged such that the undesired ?uid may sink or rise to the discharge point based density properties. If, for example, the undesired ?uid is air, the air may automatically rise toward the highest point in one or more of pump chambers 332, 334. Aisles 339 (B), 341 may be positioned to facilitate this and the discharge point may be disposed at or near that location. In some configurations, cassette sheeting 346A, 346B () may have spacer elements or other features, such as, for example, but not limited to, ribs, bumps, tabs, grooves, and channels, in addition to, or in place of spacers 337.
] Referring now to , ?rst side of ?rst cassette 282A can e pump chambers 332/334, spacers 337, walls 344, valve wells, and ports.
Referring now primarily to , second cassette 282C may be operationally r to the ?rst cassette 282A (), but may have a different layout.
Second te 282C may include one or more pump chambers, for example, ?rst pump chamber 350 and second pump chamber 352. Second cassette 282C can also include spacers 337 described ere herein. Walls 344 () and perimeter wall 345 () may be included and may project from cassette body 351. Walls 344 () may de?ne various ?uid pathways in second te 282C and may also form valve wells 380A (). Valve seat 347 () may be included in each valve well 380A (). Cassette sheeting 346A, 346B may be included as part of second cassette 282C. Cassette sheeting 346A, 346B for second cassette 282C may include preformed regions 348A, 348B for each pump chamber 350, 352. Application of pressure to cassette sheeting 346A, 346B of second cassette 282C may be coordinated to pump ?uid via pump chamber 350, 352 through a d ?ow pathway or pathways. Pushing cassette ng 346A, 346B into or pulling cassette ng 346A, 346B away from valve seats 347 may allow a desired ?ow pathway or pathways to be established.
Fill and deliver strokes may be performed in a manner which mimics a physiological characteristic or condition of a biological specimen 162 (. For example, the ?ll and deliver strokes may be synchronized in a manner which generates a pulsatile ?ow of the ?uid(s) being pumped. The rate at which ?ll strokes and deliver strokes are performed may allow for the pulse rate of the ?ow to be ed. Such adjustment may allow a cassette to mimic logical perfusion of a b iological specimen 162 (. The pressure used to execute ?ll and delivery strokes may also be varied. This pressure may be set to a value which causes the pressure of the pumped ?uid to mimic physiological perfusion pressures.
Referring now primarily to FIGS. 40 and 41, second cassette 282C can include, but is not limited to ing, ?rst side 391 () and second side 392 ().
Second cassette 282C can include, but is not limited to including, valves 3.3, 4.1-4.4, 5.1, 5.2, 9.3, 133,24, 14,21, 1.1, and 14.4. Valves 3.3, 4.1—4.4, 5.1, 5.2, 9.3, 13.3, 2.4, 1.4, 2.1, 1.1, 14.4 which may, for example, be similar to those in ?rst cassette 282A and may be independently opened and closed to make and break ?uid communication with ?uid pathways 370, 368, 364, 354, 358A, 358B, 356A, 356B () second side 392 of second te 282C. Fluid in valve well 380A (G), for example, may ?ow through valve 21 to ?uid pathway 354 on second side 392 of cassette 282C if cassette ng 346A, 346B () is not pressed against valve seat 347 () of valve 2.1. Second cassette 282C may also include ?uid ports 390, 388, 386, 384, 382, 372, 374, 376, 378, and 380. Each ?uid port 390, 388, 386, 384, 382, 372, 374, 376, 378, 380 may be connected to a ?uid line or conduit leading to ?uid source 190 (, reservoir 182 (, enclosure 100 ( or biological specimen 162 (. Operation of pump chambers 350, 352 and valves 3.3, 4.1-4.4, 5.1, 5.2, 9.3, 13.3, 2.4, 1.4, 2.1, 1.1, 14.4 may allow ?uid to be pumped into or out of second cassette 282C through any desired ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. Additionally, in some con?gurations, second cassette 282C may be con?gured such that any of pump chambers 350, 352 may be placed in ?uid communication with any of ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. id="p-279" id="p-279"
id="p-279"
[00279] Continuing to refer primarily to FIGS. 40 and 41, at least one storage reservoir port 372, 374 may be ed on second cassette 282C. Storage reservoir ports 372, 374 may be in communication with reservoir outlet lines 302C, 304C. Loop out port 378 and loop return port 376 may be in communication with ends of a loop line 308C. At least one inlet port 382, at least one outlet port 390 may also be included. Inlet port 382 may be in communication with enclosure line 319 which can transfer ?uid into/out of ure 100 (. Outlet port 390 may be in ication with an ure line 311 which may er ?uid into/out of enclosure 100 (. At least one specimen port 384, 386, 388 may be included on second cassette 282C. Specimen ports 384, 386, 388 may be in communication with specimen lines 313, 315, 317. Specimen lines 313, 315, 317 may allow transfer of ?uid to biological specimen 162 (. At least one waste port 380 may be in communication with line 306C of waste line 306A ().
Continuing to further refer primarily to FIGS. 40 and 41, among the ?uid pathways of second cassette 282C may be pump r bus 354 (), loop out bus 370 (), loop return bus 368 (), and specimen bus 364 (). Pump chamber bus 354 () may allow ?uid to be transferred between second cassette 282C and reservoir outlet lines 302C, 304C. The ?uid may, for example, be a diluted concentrate or ?uid admixture delivered to storage reservoirs 182A, 182B () from ?rst cassette 282A (). Loop out bus 370 () and loop return bus 368 () may allow ?uid to ?ow h loop line 308C from one portion of second cassette 282C to another. Specimen bus 364 () may allow ?uid to be transferred between second cassette 282C and specimen lines 313, 315, 317.
Continuing to refer primarily to FIGS. 40 and 41, second cassette 282C may include ?rst pump chamber 350 and second pump chamber 352 which may be placed in fluid communication with any of ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. While in ?uid communication with desired ) 390, 388, 386, 384, 382, 372, 374, 376, 378, 380, negative pressure may be applied to sheeting 346A, 346B () over pump chamber 350, 352 to ?ll pump chamber 350, 352 with ?uid from ?uid source 190 ( connected to the desired of ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. Positive re may be applied to expel ?uid within pump chamber 350, 352 to one or more of lines 311, 313, 315, 317, 319, 308C, 306C, 304C, 302C connected to the desired port(s) 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. Additionally, each pump chamber 350, 352 may be placed in communication with one another. Thus, the ?ow of ?uid from any of ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380 through second cassette 282C may be lled by any of pump chambers 350, 352. Only one pump chamber 350, 352 need be operable to draw ?uid into itself.
The other pump chamber 350, 352 may be left inoperable and closed off to ?ow by closing the appropriate ofvalves 3.3, 4, 5.1, 5.2, 9.3, 13.3, 2.4, 1.4, 2.1, 1.1, 14.4.
Referring primarily to , with t to pump chamber 350, communication with reservoir inlet port 372, may be established by opening valve 9.3 creating a pathway from reservoir inlet port 372 to pump chamber bus 354. Opening valve 2.1 can create a pathway from pump chamber bus 354 to ?rst pump r outlet path 356A which is in communication with pump chamber 350 via inlet/outlet 357A. Communication with reservoir inlet port 374 may be established by opening valve 5.1 creating a pathway from reservoir inlet port 374 to pump chamber bus 354. Opening valve 2.1 can create a pathway from pump chamber bus 354 to ?rst pump chamber inlet/outlet path 356A. Communication with loop out port 378 may be established by opening valve 24 creating a pathway from ?rst pump r inlet/outlet path 356B to loop out bus 370. outlet path 356B can be in communication with ?rst pump chamber 350 via inlet/outlet 357B. Communication with waste port 380 may be established by opening valve 2.4 creating a pathway from ?rst pump r outlet path 356B to loop out bus 370. Opening valve 4.1 can create a pathway from loop out bus 370 to waste port 380. Communication with inlet port 382 may be ished by opening valve 24 creating a pathway n ?rst pump chamber inlet/outlet path 356B and loop out bus 370.
Opening valve 5.2 to place loop return bus 368 in communication with inlet port 382 may complete the pathway since loop out bus 370 may be in communication with loop return bus 368 via loop line 308C. Communication with outlet port 390 may be established by opening valve 3.3 creating a pathway between outlet port 390 and pump chamber bus 354. Opening valve 2.1 would then create a pathway from the pump chamber bus 354 to ?rst pump chamber inlet/outlet path 356A. Communication with specimen bus 364 may be established by opening valve 2.4 ng a pathway between ?rst pump chamber inlet/outlet path 356B and loop out bus 370.
Opening valve 4.3 to place loop return bus 368 in communication with specimen bus 364 may then complete the pathway since loop out bus 370 may be in communication with loop return bus 368 via loop line 308C. Valves 4.2, 13.3, 4.4 may then be opened to establish communication n the desired specimen ports 384, 386, 388 and specimen bus 364.
Continuing to refer to , with respect to pump chamber 352, communication with reservoir inlet port 372, may be established by opening valve 9.3 creating a ?uid pathway from reservoir inlet port 372 to pump chamber bus 354. Opening valve 11 could create a ?uid pathway from pump chamber bus 354 to second pump chamber inlet/outlet path 358A via inlet/out 359A. Communication with reservoir inlet port 374 may be established by opening valve 5.1 creating a ?uid pathway from reservoir inlet port 374 to pump chamber bus 354. Opening valve 1.1 could create a ?uid pathway from pump chamber bus 354 to second pump chamber outlet path 358A. Communication with loop out port 378 may be established by opening valve 1.4 creating a ?uid pathway from second pump chamber inlet/outlet path 358A to the loop out bus 370. Second pump chamber inlet/outlet path 358B is in communication with second pump chamber 352 via outlet 359B. Communication with waste port 380 may be established by opening valve 14 creating a ?uid pathway from second pump chamber inlet/outlet path 358B to loop out bus 370. Opening valve 4.1 can create a ?uid pathway from loop out bus 370 to waste port 380. Communication with inlet port 382 may be established by opening valve 1.4 ng a ?uid pathway between second pump chamber inlet/outlet path 358B and loop out bus 370. Opening valve 5.2 to place loop return bus 368 in communication with inlet port 382 may complete the ?uid pathway since loop out bus 370 may be in communication with loop return bus 368 via loop line 308C. Communication with outlet port 390 may be established by opening valve 33 creating a ?uid y between outlet port 390 and pump chamber bus 354. g valve 1.1 could create a ?uid pathway from pump chamber bus 354 to second pump chamber inlet/outlet path 358A. Communication with specimen bus 364 may be established by opening valve 1.4 ng a ?uid pathway between second pump chamber inlet/outlet path 358B and loop out bus 370. Opening valve 43 to place loop return bus 368 in ication with specimen bus 364 may then te the ?uid pathway since the loop out bus 370 may be in communication with loop return bus 368 via loop line 308C. Valves 4.2, 13.3, 4.4 may then be opened to establish ication between the desired specimen ports 384, 386, 388 and specimen bus 364.
Continuing to still further refer primarily to , the ?uid pathways for placing pump chambers 350, 352 in communication with c of ports 390, 388, 386, 384, 382, 372, 374, 376, 378, 380 can be formed in many possible sequences of valve openings/closings. More than one pathway can be ished by g and closing of valves 3.3, 4.1-4.4, 5.1, 5.2, 9.3, 13.3, 2.4, 1.4, 2.1, 1.1, 14.4 of second cassette 282C to place a pump chamber 350, 352 in communication with a desired port(s) 390, 388, 386, 384, 382, 372, 374, 376, 378, 380. Additionally, multiple pump chambers 350, 352 may be placed in communication with the same port(s) 390, 388, 386, 384, 382, 372, 374, 376, 378, 380 at the same time. By opening valves 3.3, 1.1, and 2.1, all of pump chambers 350, 352 may, for example, be ed to draw ?uid from the outlet port 390. In some con?gurations, specimen ports 384, 386, 388 can allow for transfer of ?uid between second cassette 282C and specimen 162 (. If specimen 162 ( is a lung, specimen port 384, for example, may be in communication with a pulmonary artery of the lung via specimen line 317. Specimen port 386 may be in communication with a trachea of the lung via specimen line 315. Specimen port 388 may be in communication with a pulmonary vein of the lung via specimen line 313. Fluid or a mixture of ?uid such as any ?uid or any combination of those in Table I may be delivered to specimen 162 ( via second cassette 282C from storage reservoir 182A, 182B (). Fluid may also be delivered to enclosure 100 ( in which specimen 162 ( is housed via enclosure lines 319, 311 attached to inlet and outlet ports 382, 390. Once the ?uid is spent, the ?uid may be removed from the en 162 ( and , via second cassette 282C, to waste line 306C. uing to still further refer to , in some con?gurations, ?uid can, for example, proceed from a ?rst at least one loop port 376, 378 through loop line 308C, to another port such as a second at least one loop port 376, 378. At least one sensor 377 may sense a characteristic of interest of the ?uid as it passes through loop line 308C. Temperature, conductivity, turbidity, spectrophotometric teristics, ?ow rate, viscosity, color, dielectric ties, acoustic impedance dissolved gas t (e. g. dissolved oxygen), ?uorescence, dissolved organic matter, ?ow trics or any other characteristic of interest may be sensed by sensor 377 monitoring ?uid in loop line 308C. Sensor 377 may be, but is not limited to being, a thermocouple, thermistor, resistance thermometer, conductivity sensor or probe, turbidity sensor or probe, spectrophotometer, ?ow sensor, ?ow meter, velocimeter, viscosity sensor, optical sensor, capacitance probe or sensor, ultrasonic sensor, dissolved oxygen sensor, ?uorescence sensors, colored dissolved organic matter sensors (CDOM), ?uorescent dissolved organic matter sensors (fDOM), and ?ow cytometers. Sensor 377 may also monitor for a particular condition of interest. For example, sensor 377 may monitor for air bubbles in loop line 308C. In some con?gurations, sensor 377 may be, for example, an onic air bubble detection sensor, or may be a sensor similar to any of those described in US. Patent Publication No. US 2015/0033823, ?led July 25, 2014, and entitled System, Method, and Apparatus for Bubble Detection in a Fluid Line Using a Split-Ring Resonator, ey Docket No. M02 which is hereby incorporated by reference in its entirety.
Continuing to refer to , in some con?gurations, sensor 377 may be a part of a sorting system or apparatus. For example, sensor 377 may be included in a ?uorescence-activated cell sorting ?ow cytometer. In some con?gurations, a geneous mixture of cells may be separated into constituent parts using the cence—activated cell sorting (FACS) ?ow cytometer.
Continuing to refer primarily to , in some con?gurations, ?uid can also be subject to temperature regulation as it passes through loop line 308C. For example, temperature tor 379 may be placed against or in proximity to loop line 308C such that the ?uid is regulated to a desired temperature as it passes through loop line 308C. At least one sensor 377 may be ed to provide feedback as to the temperature of the ?uid in loop line 308C. Temperature regulator 379 may, for example, include any of a variety of le heating elements such as a resistive heater or number of resistive heaters. Temperature regulator 379 may also include cooling elements as well for lowering the temperature of the ?uid. Any temperature regulating elements 379, sensors 377, and other components associated with loop line 308C can be optional parts of ?uid handling set 280 (), or can be coupled to or ise ated with loop line 308C. For example, sensor 377 may clip onto loop line 308C or loop line 308C may be seated in a receiving structure of sensor 377 during set up, Referring now to FIGS. 42 and 43, second cassette 282B can be, for example, but not limited to, a mirror image of second cassette 282C, can be identical to cassette 282C, or may differ, perhaps substantially, from second cassette 282C. Second cassette 282B can include, but is not limited to including, valves 3.1, 3.2, 3.4, 9.2, 9.4, 5.3, 6.1—6.4, 14.1-14.3, .4. In some con?gurations, each valve 3.1, 3.2, 3.4, 9.2, 9.4, 5.3, 6.1-6.4, 4.3, 5.4 in second cassette 282B may have a corresponding sister valve on second cassette 282C. In some con?gurations, the same ?uid pathways between cassette ports 390, 388, 386, 384, 382, 372, 374, 376, 376B, 378, 378B, 380 and pump rs 350, 352 described in relation to second cassette 282C may be established in second cassette 282B by operating valves 3.1, 3.2, 3.4, 9.2, 9.4, 5.3, 6.1—6.4, 141—143, 5.4 in the same manner as their sister valves on second te 282C. For the configuration shown FIGS. 45 and 46, valves 3.1, 3.2, 3.4, 9.2, 9.4, 5.3, 6.1-6.4, 14.1-14.3, 5.4 of second cassette 282B and their counterpart or corresponding sister valves on second cassette 282C are provided in Table IX as follows: 3.1 13.3 .4 4.4 9.2 9.3 6.3 2.1 TABLE IX Referring now to , upstream te 282A 031G. 36) can pump ?uid to storage reservoir 182A. The pumped ?uid may be mixed inside of ?rst cassette 282A () or mixed as it is pumped into storage reservoir 182A. The ?uid stored within storage reservoir 182A may be for used by any component of ?uid handling set 280 () that can be in the ?uid pathway of e reservoir 182A, for example. In some con?gurations, ?rst cassette 282A () may also draw ?uid from storage reservoir 182A. e reservoir 182A can include inlet port 400. Inlet port 400 may attach to ?rst reservoir inlet line 286 through which ?uid may be pumped into e reservoir 182A. Storage reservoir 182A may also include reservoir outlet port 402. Outlet port 402 may be attached to reservoir outlet lines 302B, 302C through which ?uid may exit storage reservoir 182A. Fluid may, for example, be drawn from storage reservoir 182A, by second cassette 282B, 282C (). The interior volume of e reservoir 182A may vary depending on the con?guration or biological specimen 162 ( being processed. In some con?gurations, storage reservoir 182A may have an interior volume of 05-10 liters (e. g. 1.4 liters). In some con?gurations, storage reservoir 182A can have a different interior volume from storage reservoir 182B ().
Continuing to refer to , storage reservoir 182A may include a number of other ports or ori?ces. For example, storage oir 182A may include over?ow port 404. Over?ow port 404 may connect to over?ow line 294A. Over?ow line 294A may be in ?uid communication with an over?ow reservoir (not shown) which may hold excess ?uid in the event that storage reservoir 182A is over ?lled. Over?ow port 404 may include a sensor (not shown) which may provide data indicating whether the ?uid level in storage oir 182A has reached over?ow port 404. In some rations over?ow port 404 may include a conductivity sensor, for example. Storage reservoir 182A may also include at least one vent port 406. In some con?gurations, the over?ow port 404 may double as a vent port 406. In some rations, vent port 406 can be connected to vent line 298A which can include ?lter 300A.
Vent port 406 may allow air to be displaced into or out of storage reservoir 182A as the liquid level within storage reservoir 182A changes. Filter 300A on vent line 298A may, for example, but not limited to, ?lter biological material or organisms from entering into storage reservoir 182A. Filter 300A may be a 0.2 micron ?lter in some con?gurations. Filter 300A may be a hydrophobic ?lter in some con?gurations.
Continuing to still further refer to , storage reservoir 182A may also include sensor port 408. Sensor port 408 may allow for data related to the liquid level within e reservoir 182A to be collected. In some con?gurations, the type of sensor used may vary. In some con?gurations, sensor port 408 may allow for electrical communication with a sensor in storage oir 182A. The sensor may, for example, be a ?oat sensor or any other liquid level sensor. Sensor port 408 may provide pass-through for sensor line 296A or may provide a pass-through for a ?uid conduit for a manometer type sensing arrangement. Storage oir 182A may e a number of features which aid in mounting of storage reservoir 182A. For example, body 410 of the storage oir 182A may include various projections or recesses 412 therein which can facilitate attachment of storage oir 182A to another structure. Body 410 may include recesses which can accommodate clips (not shown) which can hold storage oir 182A in place on a holding structure.
Referring now to , ?rst side 411 of body 410 of storage reservoir 182A may be sloped to enable gravity to move ?uid within storage reservoir 182A toward outlet port 402 of e reservoir 182A. The sloping may, for example, facilitate full emptying of storage reservoir 182A when ?uid is transferred out of storage reservoir 182A through outlet port 402. In some con?gurations, interior inlet line 420 may extend into the interior volume of storage reservoir 182A from inlet port 400. Interior inlet line 420 may extend nearly to interior ?rst side 411A of storage reservoir 182A. Fluid entering storage reservoir 182A may pass from oir inlet line 286 through inlet port 400 to interior inlet line 420. By placing the inlet line end 420A of interior inlet line 420 near interior ?rst side 411A of e oir 182A, any splashing and mixing with air in storage reservoir 182A may be zed. Minimizing splashing and mixing in air may, for example, reduce and/or eliminate foaming or bubbling if the ?uid in storage reservoir 182A contains a surfactant, for example. In some con?gurations, the inlet line end 420 may be positioned so as to be on the opposite side of the interior ?rst side 411A than the outlet port 402. This may help to maximize mixing of various ?uids entering the storage reservoir 182A. or inlet line 420 and reservoir inlet line 286 may be continuous in some con?gurations, and in some con?gurations, may be two separate ?uid conduits.
Continuing to refer to , interior sensor line 422 can be included within the interior volume of storage reservoir 182A. In some con?gurations, or sensor line 422 may be continuous with sensor line 296A, and in some con?gurations, interior sensor line 422 may be a separate ?uid conduit from sensor line 296A. Interior sensor line 422 can extend towards and nearly to interior ?rst side 411A of storage reservoir 182A. In some con?gurations, a gap (e.g. 3-10mm) may exist between interior sensor line end 422A of or sensor line 422 and interior ?rst side 411A of storage oir 182A. Alternatively, interior sensor line 422 may touch interior ?rst side 411A and a notch, fenestration, or other void may be cut out of interior sensor line end 422A. Sensor line or end 422B of sensor line 296A may be closed such that ?uid may not enter or exit sensor line or end 422B of sensor line 296A.
In some con?gurations, sensor line exterior end 422B may be in communication with closed volume 426 in which pressure sensor 424 can reside. Pressure sensor 424 and closed volume 426 may be optionally included in ?uid handling set 280 (). Sensor line 296A of storage reservoir 182A may be coupled to closed volume 426 during set up of ?uid ng set 280 () and the closed volume 426 and pressure sensor 424 may be parts a separate durable component with which the ?uid handling set 281 interfaces. In some con?gurations an additional pressure sensor (not shown) may be included to sense ambient pressure and the ambient pressure reading may be used in conjunction with the reading from pressure sensor 424. When the ?uid level in storage reservoir 182A has covered the interior sensor line end 422A, the air (or another compressible ?uid) within the conduit of interior sensor line 422 can become compressed as the ?uid level rises. The rise in pressure within interior sensor line 422 and sensor line 296A may be monitored by pressure sensor 424. The pressure data output from pressure sensor 424 may be used to determine the liquid level within e reservoir 182A. The pressure values associated with a speci?c liquid level may be mathematically or empirically derived. ing now to A, method 1500 for generating a tissue for transplant may include, but is not limited to including, iteratively decellularizing and recellularizing 1502 a biological specimen (a synthetic scaffold may be used and will be understood to be included under the term ical specimen). A biological specimen may be a ng of cells and the associated extra cellular matrix including, but not limited to, a tissue, group of s, organ, organ system, or group of organs. The biological en may, in some rations, be porcine tissue, bovine tissue, non—human primate tissue, harvested human transplant tissue found able for transplantation, and tissue from any other source.
The ical specimen may, in some con?gurations, be a porcine lung or lungs. The biological specimen may, in some con?gurations, be decellularized and recellularized for research purposes, for example, but not limited to biological and biochemical research, or for the e of generating a transplant. The term biological specimen may be used interchangeably herein with donor tissue.
Continuing to refer to A, the protocol used to decellularize and the protocol used to recellularize the biological specimen may each be any protocol such as any known protocol. The protocol may involve delivering/removing a variety of agents, such as, for example, but not limited to, ent solutions, mediums, ?uids, biological agents, and cells to/from the biological specimen or the area around the biological specimen. A non-limiting list of potential agents which may be used in any le combination is provided in Table I. id="p-296" id="p-296"
id="p-296"
[00296] Continuing to refer to A, in some con?gurations, the protocol may be any of those bed in: Weymann, A. et al., Per?/sion-Decellularization ofPorcine Lung and Tracheafor Respiratory Bioengineering, International Center for Arti?cial Organs and Transplantation and Wiley Periodicals, Inc., 2015 (Weymann), Price, A., et al., Development ofa Decellularized Lung Bioreactor Systemfor Bioengineering the Lung: The Matrix Reloaded, Tissue Eng Part A, 2010, Aug: 16(8):2581-2591 (Price, 2010), Price, A., et al., ted Decellularization ofIntact, Human-Sized Lungsfor Tissue Engineering, Tissue Engineering: Part C, Vol. 21, No. 1, 2015 (Price 2015); Urbano, I]. et al., Lung Sca?oldsfor Bioengineered Organ, XXIV Congresso Brasileiro de Engenharia Biomedia, CBEB 2014, pp. 2814-2816 (Urbano); Taylor and Kren, United States Patent Publication # 2013/0156744, entitled Methods of Recellularizing a Tissue or Organ for Improved Transplantability, ?led February 28, 2013 (Taylor), Gratzer, P.F. et al., Matrix Alteration andNot Residual Sodium Dodecyl Sulfate xicity A?eets the Cellular lation ofa ularizedMatrix, Tissue Engineering, 2006, Oct: 12(10):2975-83 (Gratzer), and/or Sumitran-Holgersson et al, United States Patent Publication # 2014/0377864, entitled Biogenic Allogeneic Blood Vessel, ?led June 12, 2014 (Sumitran) each of which is incorporated by reference herein in its ty. Any protocol described herein is merely exemplary and non-limiting.
Continuing to refer to A, in some con?gurations, ularization and recellularization protocols for a biological specimen such as a pulmonary system may include (a) perfusing the lung(s) with deionized water and subsequently harvesting lung(s), (b) incubating the lung(s) in deionized water for 1 hour, (c) injecting deionized water into the trachea and right ventricle, (d) injecting a Triton series detergent into the trachea and right ventricle and incubating for 24 hours, (e) rinsing as in step (c), (f) injecting deoxycholate into the trachea and right ventricle, (g) ting for 24 hours, (h) rinsing as in step (c), (i) injecting sodium chloride into the trachea and right ventricle, (j) incubating for 1 hour, (k) rinsing as in step (c), (l) injecting deoxyribonuclease (DNase) into the trachea and right cle, (m) incubating for 1 hour, (11) rinsing as in step (c) using PBS, (0) ge lung(s) in growth , (p) infusing cells through the a, and (q) connecting the lung(s) to a ventilator in an incubator. In some con?gurations, the ularization protocol for a biological specimen such as a lung or lungs may e the steps of (a) perfusing PBS enriched with penicillin- streptomycin through the lung(s) and trachea for 24 hours, (b) perfusing the lung(s) with SDC and a Triton series detergent in PBS for ?ve days, (c) immersing the trachea in SDS and agitating for 72 hours and changing the solution at 24 hours, (d) washing and agitating the lung(s) with peracetic acid and l for siX hours, (e) washing the lung(s) and trachea with PBS once daily during the steps of (a)-(d), and (f) perfusing the lung(s) with PBS for 24 hours.
Continuing to refer to A, in some con?gurations, the decellularization protocol for a ical en such as a lung or lungs may e the steps of (a) freezing the lung(s) in PBS until the lung(s) is/are needed, (b) freezing/thawing the lung(s) in cycles of ten minutes each, (c) washing the lung(s) 6-8 times in PBS, (d) rinsing the lung(s) in deionized water, (e) instilling SDS in the lung(s) and agitating for 24 hours in a bath of SDS, (f) maintaining the lung(s) in SDS overnight without agitation, (g) rinsing and ing the lung(s) in PBS for 24 hours, and (h) maintaining the lung(s) in PBS without agitation. In some con?gurations, the recellularization protocol for a biological specimen such as, for example, but not limited to, a lung or lungs may include re-endothelialization of a scaffold which has been previously perfused with a buffer on, The recellularization protocol may further include introduction of epithelial cells, clara cells, goblet cells, alveolar type I, and/or alveolar type II cells into or onto a scaffold. The cells may be allowed to adhere to the scaffold for a period of time, such as, for example, but not limited to, 30 to 180 minutes. Further, the scaffold may be naturally recellularized in Vivo through the migration of cells from the adjacent tissue.
Continuing to refer to A, in some configurations, the recellularization protocol for a biological specimen may include, but is not limited to including, expanding and differentiating a population of cells. The cell population may be differentiated into elial cells and smooth muscle cells in Vitro. Introduction of the population of cells to the biological specimen may include perfusion of elial cells and smooth muscle cells.
Perfusion of an endothelial cell medium and smooth muscle cell medium may be administered in alternating fashion. Method 1500 can optionally include preparing the supplied tissue by ularizing the supplied tissue a plurality of times, and refining the tissue for transplant by decellularizing the iteratively decellularized and recellularized supplied tissue a plurality of times. Method 1500 can also optionally include ucing at least one agent to the supplied tissue, ng an undesired component of the supplied tissue with the at least one agent, and rinsing the supplied tissue. Rinsing the supplied tissue can optionally e rinsing the supplied tissue with an isotonic solution, and/or phosphate buffered solution The at least one agent can optionally e a detergent, a Triton series detergent, sodium dodecyl sulfate, peracetic acid, ethanol, an enzyme solution, a nuclease, DNase, RNase, water, zed water, and/or distilled water. Method 1500 can optionally e freezing the supplied tissue, and alternately freezing and g the supplied tissue. id="p-300" id="p-300"
id="p-300"
[00300] Continuing to still further refer to A, method 1500 can optionally include, but is not d to including, introducing the biological specimen to at least one agent for a period of time. The at least one agent may include, but is not limited to including, a detergent (eg. a Triton series detergent such as Triton X-100), enzyme (eg. a nuclease such as DNase or RNase), enzyme tor, chelating agent, cell lysing agent, osmotically incompatible agent, anti—microbial agent (eg. anti—biotic, Peracetic acid), water, alcohol (eg. ethanol), and any suitable agent from Table I. The biological specimen may be uced to the at least one agent in any of a number of ways. In some con?gurations, the at least one agent may be perfused through an anatomical eway of the biological specimen and/or the biological specimen may be bathed in the at least one agent. Method 1500 may optionally include preparing the biological specimen for decellularization. Preparation may include cleaning and rinsing the biological en and/or readying anatomical structures of the biological specimen for decellularization by, for example, but not limited to, attaching tubing and ligating vasculature.
In some con?gurations, method 1500 may further include agitating, for example, but not limited to, mechanical and through tion, the biological specimen. In some con?gurations, method 1500 may further include regulating the temperature of the biological specimen and/or at least one agent before, during, and after ularization. uing to refer to A, recellularization can optionally include introducing a cell culture to the decellularized supplied tissue, introducing endothelial cells, epithelial cells, clara cells, ciliated cells, goblet cells, alveolar type 1, and/or ar type II cells to the decellularized supplied tissue, and/or ucing stem cells or cells of at least one tissue speci?c phenotype to the decellularized supplied tissue. Recellularizing can also optionally e ucing cells to an acellular scaffold which may be, but is not limited to being, an isolated ECM scaffold or a synthetic scaffold. In some con?gurations, the ld may be created via method 1500. Introducing cells may be done in any of a number of ways. In some con?gurations, the cells may be perfused through an anatomical eway of the biological specimen and/or the biological specimen may be bathed in the cells. In some con?gurations, introducing cells may include perfusing different types of cells through assigned anatomical passages. In some con?gurations, the cells introduced may be epithelial cells, endothelial cells, elial cells, mesenchymal cells, etc. Depending on the biological en, more speci?c specialized cell types or cells with tissue speci?c phenotypes may be introduced which are appropriate to the specimen. In a lung, in some con?gurations, clara cells, ciliated cells, goblet cells, alveolar type I, and/or alveolar type II cells, may be introduced. In some con?gurations, hepatocytes may be introduced if the biological specimen is a liver for example. In some con?gurations, cardiomyocytes may be introduced if the biological specimen is a heart. Other ies of cells may also be introduced such as e uncommitted or pluripotent cells such as stem cells, itor cells, precursor cells, and/or fetal associated cells. Introducing cells may include introducing cells which are autologous to the intended recipient or non-immunogenic to the intended recipient. Method 1500 may optionally Method 1500 may optionally include regulating the temperature of the biological specimen and/or at least one recellularization agent before, during, and after recellularization. In some con?gurations, method 1500 may optionally include simulating a physiological condition. In some con?gurations, pulsatile blood ?ow or ing may be simulated. ing now to B, method 1550 for decellularizing and recellularizing a biological en may include, but is not limited to including, decellularizing 1552 a biological specimen with a ?rst decellularization ol. Method 1550 may further include recellularizing 1554 the biological specimen with a ?rst recellularization ol.
Method 1550 may also include decellularizing 1556 the biological specimen with a second decellulaIization protocol. Method 1550 may include recellularizing 1558 the biological specimen with a second recellularization protocol. The second decellularization protocol and the second recellularization protocol may differ in whole or in part respectively from the ?rst decellularization protocol and ?rst recellularization protocol. The ?rst and second decellularization protocols and the ?rst and second recellularization protocols may optionally each use the same agents or may use at least one different, some different, or all different agents.
In some con?gurations, one of the ?rst decellularization protocol or the ?rst recellularization protocol may be used a second time when decellulaiizing 1556 or recellularizing 1558.
Continuing to refer to B, the ?rst decellularization protocol may use at least one of a ?rst set of decellularization agents, and the second decellularization protocol may use at least one of a second set of decellularization agents. The ?rst set of decellularization agents can optionally include at least one decellularization agent, and the second set of decellularization agents can optionally include at least one decellularization agent. The ?rst set of decellularization agents can optionally be substantially the same as or identical to the second set of decellularization agents or the ?rst set of ulaiization agents can optionally be different from the second set of decellularization agents. The ?rst recellularization protocol may use at least one of a ?rst set of recellularization agents, and the second recellularization protocol may use at least one of a second set of recellularization . The ?rst set of recellularization agents can optionally include at least one recellularization agent, and the second set of recellularization agents can optionally include at least one recellularization agent. The ?rst set of recellularization agents can ally be substantially the same as to the second set of ularization agents or the ?rst set of recellularization agents can optionally be ent from the second set of recellularization agents. The protocols may be de?ned by differing temporal ters. In some con?gurations, the protocols may include steps which can be performed for greater or lesser periods of time and/or steps within a protocol may be temporally rearranged and performed in s orders.
Continuing to refer to B, if 1560 "n" number of iterations have been completed, method 1550 may ate. The variable "11" may be any number of iterations and may be prede?ned or determined dynamically by, for example, but not limited to, examining the status of the processed biological specimen. If 1560 "11" number of iterations have not been completed the biological en may be decellularized 1556 and recellularized 1558 again until the number of iterations completed is equal to "n". In some con?gurations, each ion may use protocols which are ent from any previously used protocol. A ?rst iteration may use the ?rst decellularization protocol and the ?rst recellularization protocol, a second iteration may use the second decellularization protocol and the second ularization protocol, and so on. In some con?gurations, each iteration may use a previously used protocol or a different protocol. In some rations, the protocols used in method 1550 may ate based on which part of method 1550 is being executed. For example, the protocols used in 1552, 1554 and 1556, 1558 may be used in alternating fashion throughout multiple iterations. In some con?gurations, a select number of different decellularization protocols and recellularization protocols may be scheduled for use on speci?c iterations. The number of different decellularization protocols may differ from the number of different recellularization protocols.
Continuing to still further refer to B, in some con?gurations, the protocol used for decellularization in each iteration may remain the same while the protocol used for ularization in each iteration can be changed (or vice versa). In some con?gurations, the protocol used for decellularization in each iteration may be altered at a ?rst rate (e. g. after every ?rst number of iterations) while the protocol used for recellularization can be altered at a second rate (eg. after every second number iterations).
] Referring now to C, method 1590 for decellularizing and ularizing a biological specimen may include, but is not limited to including, decellularizing 1580 a biological specimen with a ularization protocol. If 1582 all decellularization cycles for the current ion of method 1590 have not been completed, decellularization 1580 of the biological specimen may be repeated. If 1582 all decellularization cycles for the current iteration have of method 1590 have been completed, method 1590 may include recellularization 1584 of the biological specimen with a recellularization protocols If 1586 all recellularization cycles for the current iteration of method 1590 have not been completed, recellularization 1584 of the biological specimen may be repeated. If 1586 all ularization cycles for the current iteration of method 1590 have been completed, and if 1588 "n" iterations of method 1590 have been completed, method 1590 may terminate. If 1586 all recellularization cycles for the current iteration of method 1590 have been ted, and if 1588 "n" ions of method 1590 have not been completed, method 1590 may return to decellularizing 1580. The variable "n" may be any desired number of iterations and may be prede?ned or dynamically determined based on, for e, but not limited to, the status of the biological specimen. uing to refer to C, protocols in each iteration of method 1590 may differ from each other, for example, similarly to as described above in relation to . In some con?gurations, within each iteration, decellularization and recellularization may each (though not necessarily both) be done multiple times and the number of times for each may be prede?ned or determined dynamically based on, for example, but not d to, the status of the processed biological specimen. In some con?gurations, each time a decellularization protocol or recellularization protocol is performed within an iteration, the protocol used may be the same as at least one or differ from each protocol performed previously. The protocols may use at least one different, some, or all different agents, for example, In some rations, protocols which differ from one another may be de?ned by differing temporal parameters. In some con?gurations, the protocols may include steps which are performed for greater or lesser periods of time and/or steps within a protocol may be temporally nged and performed in a different order. In some con?gurations, there may be multiple cycles of both ularization and recellularization protocols within an iteration. In some con?gurations, one of the ols for decellularization and recellularization may differ from cycle to cycle, while the other may be constant or maintained. In some con?gurations, the decellularization protocol may be maintained, while the cell type(s) introduced in the recellularization protocol may differ from cycle to cycle. In some con?gurations, a select number of different ularization protocols and recellularization protocols may be scheduled for use on speci?c . Different protocols for ularization and recellularization may be used in ating fashion over a number of cycles. In some con?gurations, the protocol used for decellularization in each cycle may be altered at a ?rst rate (e. g. after every ?rst number of cycles) while the protocol used for recellularization is altered at a second rate (e. g. after every second number cycles). id="p-308" id="p-308"
id="p-308"
[00308] Referring now to D, method 1530 for a generating a transplantable lung from a donor lung may include, but is not limited to including, decellularizing 1532 the donor lung. Method 1530 may include recellularizing 1534 the decellularized lung. Method 1530 may include ularizing 1536 the recellularized lung. Method 1530 may include creating 1540 the transplantable lung by recellularizing the lung from 1536 if 1538 "11" number of iterations have been completed. The variable "n" may be any number of desired ions and may be prede?ned or determined dynamically based on, for example, but not limited to, the status of the processed donor lung. Method 1530 may include repeating ularizing 1534 the lung and decellularizing 1536 the lung if 1538 "n" number of iterations have not been completed.
In some con?gurations, method 1530 may also be used for other biological specimens. In some con?gurations, the iterations may be conducted as described in relation to FIGs. 63 and 64. id="p-309" id="p-309"
id="p-309"
[00309] Referring now to , ?tting 460 can include, but is not limited to including, sensor well 462. Sensor well 462 can form a pathway leading to the interior of ?tting 460. Sensor well 462 can be, but is not limited to being, located on the main portion or body 472 of ?tting 460 and can be de?ned in part by surrounding wall 478 that can, for example, project away from main portion 472. Surrounding wall 478 may, for example, but not limited to, project from main portion 472 in a manner substantially perpendicular to the long axis of ?tting 460. In some rations, main portion 472 may be ted and may include multiple sensor wells 462.
Fitting 460 can also include connector tion 464 which may optionally, but not necessarily, include a number of barbs 466. In some con?gurations tor projection 464 may be Luer-lock like connector projections. Fluid conduit 468 may couple onto connector projection 464 such that ?uid may pass from conduit 468 into the interior of ?tting 460. In some con?gurations, ?uid conduit 468 may be ently attached to connector projection 464 via e. g. solvent g.
Continuing to refer to , ?tting 460 can also include mating body 470 which can extend from main portion 472 of ?tting 460. Mating body 470 may be con?gured to mate and lock onto r, ly identical, ?tting 460. For example, mating body 470 may include arm 474 which can have mating face 476 that can mate and lock to another ?tting 460. Mating face 476 may include ramp 480 which can begin at end 484 of arm 474. Ramp 480 may progressively increase the thickness of arm 474 in a direction toward main portion 472 of ?tting 460 as the ramp 480 extends away from the end 484. Mating face 476 may also include a detent region or dwell 482 which can be separated from ramp 480 by transition region 486 at which the ess of arm 474 can be greatest. Detent region 482 may be a depression into arm 474 which can decrease the thickness of arm 474. Detent region 482 may be a curved shape depression, or in some con?gurations may be de?ned by a lip or step down from transition region 486. In some con?gurations, the thinnest part of detent region 482 of arm 474 may be thicker than the thinnest part of ramp 480. Fitting 460 can also include gasket 488.
Gasket 488 may be any of a variety of suitable sealing members. Gasket 488 may be ucted of a compliant, compressible material such as an elastomeric material. Gasket 488 may be, for example, but not limited to, a planar gasket or an o-ring. In some rations, when two ?ttings 460 are mated to one another, gasket 488 of each ?tting 460 may abut and be compressed to create a ?uid tight seal between ?ttings 460.
Referring now to the progression of FIGS. 48A and 48B, two ?ttings 460A, 460B are shown being mated er. In the ?rst stage of mating shown in A, ?ttings 460A, 460B may be brought into proximity with one another. Main portions 472A, 472B of each ?tting 460A, 460B may be cradled in mating body 470A, 470B of the other. One of ?ttings 460A, 460B may be rotated until ramps 480A, 480B of ?ttings 460A, 460B abuts surrounding walls 478A, 478B of the other of ?ttings 460A, 460B. Fittings 460A, 460B may be rotated in opposite directions or one of ?ttings 460A, 460B may be held stationary while the other of ?ttings 460A, 460B is rotated.
] Referring now primarily to B, when ramps 480A, 480B abut nding walls 478A, 478B, ?ttings 460A, 460B may continue to be rotated in the second stage of mating. In some con?gurations, the se in thickness of ramps 480A, 480B, may cause ramps 480A, 480B to act in a ke manner. Ramps 480A, 480B may t the rotational displacement into a linear displacement by applying a force against surrounding walls 478A, 478B of ?ttings 460A, 460B urging them toward one r. As compared to A, gaskets 488A, 488B in B are compressed against one another as a result of the further rotation. At the end of the second stage of mating, surrounding walls 478A, 478B may be in contact with transition region 486B of the arm 474A, 474B (A).
Referring now to C, ?ttings 460A, 460B may continue to be still further rotated into a fully mated and locked state. The further rotation of ?ttings 460A, 460B may cause detent region 482A, 482B of each arm 474A, 474B to rest against a portion of surrounding walls 478A, 478B of the opposing ?tting 460A, 460B. In this position, mating faces 476A, 476B may apply a force against surrounding walls 478A, 478B which can compress gaskets 488A, 488B of each ?tting 460A, 460B. The compression of gaskets 488A, 488B may form a ?uid tight seal between the environment and the interior of ?ttings 460A, 460B. Detent s 482A, 482B may be shaped complimentarily to surrounding walls 478A, 478B to allow detent regions 482A, 482B to cradle nding walls 478A, 478B.
Continuing to refer to C, the interaction of detent region 482A, 482B and surrounding walls 478A, 478B may serve to help protect t inadvertent disassociation of ?ttings 460A, 460B or may lock them together. In order to disassociate ?ttings 460A, 460B from one another, a rotational force may be applied which can force ?ttings 460A, 460B toward one another and ss gaskets 488A, 488B. Detent regions 482A, 482B and transition regions 486A, 486B may be shaped to tune the amount of force required to disassociate ?ttings 460A, 460B from one another. The thicker are transition regions 486A, 486B in comparison to detent regions 482A, 482B, the greater the force required to disassociate ?ttings 460A, 460B from one r. The amount of force desired may be chosen to allow ?ttings 460A, 460B to be separated without undue effort, but with enough force that accidental disassociation is unlikely. Alternatively, the amount of force required may be selected such that it is very hard to disassociate two mated ?ttings 460A, 460B to, for example, dissuade against reuse.
Continuing to refer primarily to C, ?ttings 460A, 460B can be permanently associated after they are mated by using additional or alternative mating structures.
In some con?gurations, s 460A, 460B may e features which render them inoperative if disassociated after being mated. In some con?gurations, arms 474A, 474B may include a cable ke projection which can include an integrated gear rack. Each of mating bodies 470A, 470B (B) may include a pawl or ratcheting mechanism which can be sized to accept the rack projection of the opposing of arms 474A, 474B. When joined, the ratcheting mechanism may prevent ociation of ?ttings 460A, 460B. Any other arrangement to prevent disassociation may also be used.
Referring now to FIGS. 49A-D, a number of views of ?ttings 460A, 460B which have been mated and locked together are shown. Each of ?ttings 460A, 460B may include sensor well 462 () which can be de?ned at least in part by surrounding walls 478A, 478B. Sensor 490 may be placed or housed in each sensor well 462 (). Sensor 490 may be any of a variety of sensors. Temperature, tivity, turbidity, spectrophotometric, ?ow rate, color, dielectric property, air bubble, acoustic impedance sensors, or any other sensors mentioned herein may, for example, be used. In some con?gurations, sensors 490 can be conductivity sensors. In some con?gurations, when multiple of sensors 490 are used, sensors 490 can be different from one another. In some con?gurations, sensor 490 may only be included for one of ?ttings 460A, 460B. In some con?gurations, ?ttings 460A, 460B can have an elongated of main bodies 472A, 472B (E) including multiple sensor wells 462 (). Single ?ttings 460A, 460B may have sensors 490 for multiple different characteristics of interest. id="p-318" id="p-318"
id="p-318"
[00318] Referring now ily to E, a cross sectional view of two mated ?ttings 460A, 460B taken at line 1 of A is shown. Connector projections 464A, 464B may each include tor ?uid conduits 492A, 492B extending hrough and leading to sensing volumes 494A, 494B. When ?ttings 460A, 460B are mated and locked together, the seal created by gaskets 488A, 488B may join sensing volumes 494A, 494B in a ?uidically sealed manner creating sensing chamber 496. Fluid may pass from ?uid line or conduit 468 (FIG, 47) attached to one of connector projections 464A, 464B through connector conduits 492A, 492B and sensing chamber 496 to another of ?uid line 468 () attached to the other of connector projections 464A, 464B. Sensors 490 may be introduced to sensing chamber 496 via sensor wells 462A, 462B. A characteristic of the ?uid may be sensed by s 490 while the ?uid is within sensing chamber 496. If sensors 490 are conductivity sensors, sensing chamber 496, may for example, be sized such that the working portion of probe 498 of sensor 490 may be completely bathed in the ?uid being sensed. In some con?gurations, dimensions of ?ttings 460A, 460B may be selected to place sensors 490 a desired distance apart from one another. In some con?gurations, gaskets 488A, 488B may be d or swapped out to alter the distance between sensors 490. In some con?gurations, the distance between sensors 490 may be about 0.4-0.8 inches apart. In some con?gurations, the distance n s 490 (from center point to center point) may be about 0.6 inches. Alternatively, the distance may be greater, for example between 3.5-2 inches. The ce chosen may be dependent on the concentration ranges expected. Generally, if the expected tration ranges are lower the ce may be r. In some con?gurations, a light source can be included as part of sensor 490 or within the sensing chamber 496. In some con?gurations, the light source may, for example, be an LED light source.
] Continuing to refer primarily to E, in some con?gurations, connector projections 464A, 464B may be of differing sizes allowing mated s 460A, 460B to act as adapters between different diameter ?uid lines 468 (). One of connector projections 464A, 464B may be sized to ?t a ?rst er line while the other can be sized to ?t a second, different size, diameter line. Sensor wells 462 () and sensors 490 can be optional in some con?gurations where s 460A, 460B serve as adapters.
Referring now primarily to , ?tting 500 can include, but is not limited to including, connector projection 464 which can optionally include barbs 466, though other varieties may also be used. Connector projection 464 may be attached to ?uid line or conduit 468 (). Fitting 500 may include main body 472 and mating body 470. Main body 472 may include sensor well 462 () which can be de?ned at least in part by surrounding wall 478. Sensor well 462 () may be in communication with sensing volume 494 on the interior of ?tting 500. Main body 472 may include track 502 which can be recessed into outer face 504 of main body 472. Track 502 may have, for example, but not limited to, a detent or dwell region 503. Mating body 470 may be con?gured to mate and lock with another ?tting 500 which may be identical to ?tting 500. Mating body 470 may include projection 506 which can be sized to ?t within track 502 of another ?tting 500. When projection 506 is engaged with track 502 of another ?tting 500, two ?ttings 500 may be rotated and mated. As projection 506 rides along track 502 toward detent region 503, the onal cement of two ?ttings 500 can be translated to a linear displacement. The linear displacement may force two ?ttings 500 toward one another. When projection 506 reaches detent region 503, two ?ttings 500 may be fully mated and locked. Lip 505 that can de?ne the ry between track 502 and detent region 503 may help lock s 500 together and may protect against rtent disassociation of two ?ttings 500. In some con?gurations, an undercut (not shown) may be included along at least one wall of the track 502. Projection 506 may e a cooperating feature which mates into the undercut and helps secure two ?ttings 500 together. Gasket 488 () may be placed in recess 508. Gasket 488 may become compressed which can create a ?uid-tight seal between two ?ttings 500 during mating.
Referring now to FIGS. 51B—D, a number of views of two ?ttings 500A, 500B which have been mated and locked together are shown. Each of ?ttings 500A, 500B may include sensor well 462 which can be de?ned at least in part by surrounding wall 478A, 478B.
Sensor 490 may be placed or housed in each sensor well 462. Sensor 490 may be any of a variety of sensors, for example, but not limited to, sensors described herein. Sensors 490 in each sensor well 462 can differ from one another. In some con?gurations, sensor 490 may be ed for only one of ?ttings 500A, 500B. ing now primarily to E, a cross sectional view of two mated s 500A, 500B taken at line 27F-27F of D is shown. Projections 506A, 506B of each mating body 470A, 470B may be in contact with the detent region 503A, 503B of the opposing ?tting 500A, 500B track 502A, 502B. Thus, the ?ttings 500A, 500B may be fully mated and locked together. Gasket 488 may be ssed, joining g volumes 494A, 494B in a ?uidically sealed manner creating sensing chamber 496. Connector projections 464A, 464B may each include connector fluid conduit 492A, 492B extending therethrough and g to respective sensing volumes 494A, 494B. Fluid may pass from ?uid line or conduit 468 () attached to one connector tion 464A, 464B through the connector conduits 492A, 492B and sensing chamber 496 to another ?uid line 468 () attached to the other connector projection 464A, 464B.
Continuing to refer to E, Sensors 490 may be introduced to sensing chamber 496 via sensor wells 462A, 462B. A characteristic of the fluid may be sensed by sensors 490 while the ?uid is within sensing chamber 496. If sensors 490 are tivity sensors, sensing chamber 496, may, for example, be sized such that the working portion of sensor 490 may be completely bathed in the ?uid being sensed. Dimensions of ?ttings 500A, 500B may be selected to place sensors 490 a desired distance apart from one another. In some con?gurations, the ce between sensors 490 (from center point to center point) may be about 0.4-0.8 inches. In some con?gurations, the distance between s 490 may be about 0.6 inches. Alternatively, the distance may be greater, for example between 3.5-2 inches. The distance chosen may be dependent on the concentration ranges expected. Generally, if the expected concentration ranges are lower the distance may be shorter.
] Referring now to A ?tting 650 can include, but is not limited to including, connector projection 652 which can optionally include barbs 654, though other varieties may also be used. tor projection 652 may be attached to ?uid line or conduit 468 (). Fitting 650 may include main body 656, ?rst mating body 658 and second mating body 660. Main body 656 may include sensor well 662 which can be de?ned at least in part by surrounding wall 664. Sensor well 662 may be in communication with a sensing volume on the interior of ?tting 650.
Continuing to refer to A, ?rst mating body 658 may include cantilevered beam 666 which can extend from main body 656 substantially parallel to the long axis of ?tting 650. Cantilevered beam 666 may include a catch or latching structure 668. The catch 668 may be at an end 670 of the ?rst mating body 650. The end 670 may be distal to the main body 656. In some con?gurations, the catch 668 may include a sloped portion which increases the thickness of the cantilevered beam 666 as it extends from end 670 proximally toward main body 656. The catch 668 may also include a lip 674 which de?nes the end of the sloped portion 672. The sloped n 672 may have a gentle slope or slope between 30-50 degrees, though the slope may differ in other con?gurations. id="p-326" id="p-326"
id="p-326"
[00326] Continuing to still further refer to A, ?tting 650 may mate with a second ?tting which may, in some con?gurations, be an cal ?tting. Second mating body 660 may, for example, be con?gured to receive a ?rst mating body 658 of another ?tting 650.
The second mating body 660 may include a slot or bay 676 into which a ?rst mating body 658 of another ?tting 650 may be uced. In some con?gurations, the bay 676 may completely nd the ?rst mating body 658 when the ?rst mating body 658 has been introduced. The bay 676 may include an opening 678 through which the end 670 of a ?rst mating body 658 may protrude.
Referring now to FIGS. 52B-C, during mating of two ?ttings 650A,B, the ?ttings 650A,B may be aligned such that the ?rst mating bodies 658A,B of ?ttings 650A,B are in line with second mating bodies 660A,B of the opposing ?tting 650A, B. When the ?rst mating bodies 658A,B begin to enter the receiving second mating bodies 660A,B, the sloped portions 672A,B may cause the cantilevered beams 666A,B to be de?ected inward toward the long axis of ?ttings 650A, B. The two ?ttings 650A,B may continue to be brought together until they reach the position shown in C. id="p-328" id="p-328"
id="p-328"
[00328] Still referring to FIGS. 52B-C, once the two ?ttings 650A,B are fully mated er, the ends 670A,B of ?rst mating bodies 658A,B may t through openings 678 (A) of their ing second mating bodies 660A,B. When the sloped portions 672A,B have d g 678 (A) cantilevered beams 666A, B may restore to a resting or unde?ected position. In this position, lips 674A,B may abut against walls 680A, B of their respective second mating bodies 660A, B locking the two ?ttings 650A,B together. As in above con?gurations, a gasket 488 () may be placed in between the two s 650A,B when they are mated and locked together. Gasket 488 () may become compressed which can create a ?uid-tight seal between two ?ttings 650A,B during mating.
Referring now to C, a sensor 490 (E) may be placed or housed in each sensor well 662. Sensor 490 may be any of a variety of sensors, for example, but not limited to, sensors described herein. Sensors 490 (E) in each sensor well 662 can differ from one another. In some con?gurations, sensor 490 (E) may be included for only one of ?ttings 650A, 650B. Fluid may pass from ?uid line or conduit 468 () attached to one connector projection 652A, 652B through the ?ttings 650A, 650B to another fluid line 468 () ed to the other connector projection 652A, 652B. s 490 (E) may sense at least one characteristic of the ?uid as the ?uid passes through the ?ttings 650A, B. The ?ttings 650A, B may be red to accommodate or space apart sensors 490 as described above. ing now to A, an example of second cassette 282C which can include a loop line 308C is shown. Fitting assembly 510 can include, for example, but not limited to, a pair of mated ?ttings 460A, 460B (C) between ?rst loop portion 514A and second loop portion 514B of loop line 308C. Fitting assembly 510 can include, but is not limited to including, two sensors 490 from which electrical communication lines 512 can extend.
Sensors 490 may sense a characteristic of ?uid passing through loop line 308C such as the conductivity of the ?uid. Any other characteristic and/or condition may also be sensed. A signal representative of a sensed value for the characteristics and/or condition of interest may be reported via ical communication lines 512.
Referring now primarily to B, enclosure 100 can e, but is not limited to including, ?uid lines 311, 313, 315, 317, 319 that may be attached to or extend into a bag containing specimen 162 ( as described elsewhere . In some con?gurations, one oflines 311, 313, 315, 317, 319 may include a ?rst portion and a second portion which are separated by ?tting assembly 510. Fitting assembly 510 may serve as an adapter between tubing of differing sizes in some con?gurations. Fitting assembly 510 may include sensors 490 which may sense a characteristic and/or condition of the ?uid entering or exiting enclosure 100 or biological specimen 162 ( in ure 100. In some con?gurations, line 319 may include ?rst portion 516A and second portion 516B which can be ted by and attached to ?tting assembly 510 including sensors 490. Sensors 490 may sense any characteristics and/or condition of interest of the fluid passing h ?tting assembly 510, for example, tivity.
A signal entative of a sensed value for the condition of interest may be reported via electrical communication lines 512.
Referring now to , in some con?gurations, an example ?uid ng set 280 () may include one or more pierceable septum 530. Septum(s) 530 may be made of a self closing or sealing material such as a rubber or elastomer which may be pierced by a sharp instrument such as a needle. Septum(s) 530 may form a ?uid tight seal between the surrounding environment and the interior of ?uid handling set 280 () Septum(s) 530 may serve as sampling ports through which a sample of ?uid or biological specimen 162 ( 1) within ?uid handling set 280 () may be drawn. After drawing the sample, the hole in septum 530 may close and septum 530 may again provide a ?uid tight r. The sample may then be analyzed to determine various characteristics of the sample. For e, a cell count may be taken or components of the sample may be separated and stained for later analysis. In some con?gurations, at least one septum 530 may be included as part of enclosure 100. Septum 530 may be attached to a piece of material which is then heat bonded, solvent bonded, attached with adhesive, ultrasonically welded, or otherwise attached to enclosure 100. Septum 530 may allow ng of the contents of enclosure 100. In some con?gurations, ?uid may be drawn from enclosure 100 or part of biological en 162 ( contained within ure 100.
Septum 530 may be placed at any le location on enclosure 100. In some con?gurations, septum 530 may be placed near adapter 23 (.
Referring now primarily to A, at least one septum 530 may be disposed in other portions of ?uid handling set 280 (). In some con?gurations, septum 530 may provide access to ?uid ?owing through a ?uid line of ?uid handling set 280 ().
Any ?uid line within ?uid handling set 280 () may be in communication with septum 530 which may be used as a sampling port. In some con?gurations, in lieu of or in addition to sensor 490 (E), ?tting 460 may include septum 530. Septum 530 may, in some con?gurations, be placed in sensor well 462 of ?tting 460. In some con?gurations, a needle or other sharp instrument may pierce through septum 530 to gain access to the ?uid within ?tting 460. Septum 530 may be made of a self healing material and may re-seal itself upon withdrawal of the piercing instrument.
Referring now to B, in some con?gurations, a dual (or triple, quadruple, so on) septum 532 may be included as part of ?uid handling set 280 (). In some con?gurations, a plurality of septa 532A, 532B may be placed in series with one another.
Each septum 532A, 532B may be pierced to gain access to the ?uid to be d. Multiple septa 532A, 532B can provide ant ?uid tight seals between the environment and the ?uid.
In some con?gurations, a plurality of septa 532 may be included in many places in ?uid handling set 280 () such as in enclosure 100 ().
Referring now to C, valves and pump chambers of tes 282A- C () may be actuated by any suitable type of pneumatic valves. In some rations, the valves may be included in valve modules which may each comprise one or more valves.
Additionally, each valve module may contain all of the electronic components necessary to operate the valves included in that valve module. A valve module may thus be an assembly of one or more valves attached to one or more PCBs populated with electronic components suitable for operating the valves autonomously or semi-autonomously with respect to main or central controller 2047 (). This may help to of?oad some of the computing ces necessary to run the valves from a main processor of a device. Controller 2047 () may then only need to send a valve module high level commands. These high level commands may include start commands, stop commands, resume ds, and commands to perform template functions pre-programmed on the PCB. Alternatively, the PCB may allow a valve module perform a valve function in an entirely autonomous manner without the need for an external ller. Still further, control may be centralized in the main processor. Any of the example methods, systems, and valves described in US patent application serial number 14/967,093, ?led December 11, 2015, and entitled Modular Valve Apparatus and System, Attorney Docket No.
P82, incorporated herein in its ty, may, for example, be used.
Continuing to refer to C, valves such as binary , vari-valves, or any of the valves bed herein may, in some con?gurations, be supplied as modular that can be plugged into a manifold frame or base to provide pneumatic, hydraulic or electrical control of external devices, such as ?uid ?ow control devices, heaters, motors, or hydraulic or pneumatic devices. Each valve module 2800 can include one or more valves 2802. Each valve module 2800 may include electronic components necessary to operate valves 2802 included in valve module 2800. The electronic components can include an electronic controller equipped to perform a number of programmed commands to the valves to allow valve module 2800 to actuate or control an external device in at least a partially autonomous manner. Valve module 2800 can include an assembly of one or more valves 2802 connected to one or more on-board PCBs 2808 populated with electronic components suitable for operating the valves autonomously or semi—autonomously with t to a main or central controller. Some of the computing resources necessary to run valves 2802 can be performed by the on-board PCBs 2808, and others can be performed by a main processor of the lled device, for example. The main processor can supply high level commands to valve module 2800 such as, for example, but not d to, start commands, stop commands, pause/resume commands, commands to perform a ement, commands to e liquid ?ow in an associated flow control device, commands to properly sequence the operation of on-board , commands to coordinate valve actions among a local group of s, and commands to perform template functions pre- programmed on PCB 2808. PCB 2808 can command valve module 2800 to m a valve function (e.g., opening or closing a port in a prescribed sequence or at a prescribed rate) in an autonomous manner without further input from an external controller. id="p-337" id="p-337"
id="p-337"
[00337] Continuing to refer to C, in some con?gurations valve ld module 2800 can include a plurality of valve assemblies 2802, and PCB 2808 may be con?gured such that all of the valves 2802 in the module 2800 may be ed using a common power source or bus. In some con?gurations, module 2800 can include multiple valve assemblies 2802, each of the valve assemblies 2802 being mounted on modular ld base 2804 which can include or can be operably connected to ld ?uidic (hydraulic or pneumatic) ?ow paths (?uid buses) for valves 2802. An integrated manifold assembly can include a plurality of concatenated valve manifold s 2800 that can be assembled (attached or connected together, for example by fasteners) and con?gured for l or operation of an al device, such as a liquid flow control device (e.g. pump and valve device for transfer of a liquid). A modular valve/manifold assembly can permit maintenance, repair or replacement of individual valve modules 2800 by plugging in or unplugging the valve module 2800 from the manifold.
Each valve module 2800 can include a bank of valve assemblies 2802. Value assemblies can include ports and electrical connections and housing dimensions that can be suf?ciently cal to be interchangeable among the designated receptacles in module 2800. Valve manifold module 2800 can be con?gured for operation of an al device having various features or functions, for example, but not limited to, various arrays of ?uid ?ow control pumps and valves, and/or systems with various electronic, electrical, hydraulic or pneumatic functions.
Continuing to still further refer to C, each PCB 2808 may include, for example, a pressure sensor which is con?gured to read the pressure of a ?uid volume in the module. In some con?gurations, the re sensors may read the pressure from wells in the module manifold or block 2804 where the wells can ?uidically communicate with the ?uid pathways in module block 2804. O-rings, gasketing, and/or another suitable seal, for example, may ly isolate the volume of the wells in module block 2804 from the ambient environment. In some con?gurations, one or more o-rings and/or gaskets may be compressed to create the seal as PCB 2808 is coupled to module block 2804. In other con?gurations, the re s of PCB 2808 may communicate with the interior valve cavities of valves 2802 via any suitable ?uid path. In some con?gurations, pressure sensors may be, for e, in ?uid communication with the interior valve cavities directly through a ?uid path in each of the respective valves 2802. In some con?gurations, pressure sensors may be in communication with the ?ow paths leading from outlets of values 2802 via a ?ow path through end blocks 2806 on the ends of module 2800. Other arrangements may also be used.
Continuing to refer to C, sensors, such as, for example, but not limited to, t sensors, may also be included on PCB 2808. Current sensors may be con?gured to sense the t running through the electromagnetic coils of valve 2802, for example. Data provided by the current sensors may allow for a determination to be made about whether or not valve 2802 is functioning properly. PCB 2808 may also be equipped to receive electronic s from remote sensors, and to convert these signals to l form using any suitable A/D converter mounted to on PCB 2808. Remote sensor signals may be received from remote pressure sensors, conductivity sensors, temperature sensors, air—in-line sensors, ?uid level sensors, ?ow sensors, as well as other types of s depending on the application to which the valve/controller module is directed. A processor or processing components may be included on PCB 2808 and may allow valve module 2800 to autonomously execute various valve-related applications. Module 2800 may require little or no direction from an external processor included in the device in which module 2800 is installed. The sor or processing components of PCB 2808 may make use of and analyze data ted from other components (e.g. pressure sensors) of PCB 2808 to meet the needs of a particular application.
Continuing to refer to C, modules 2800 can be con?gured and programmed for particular applications. Modules 2800 may be programmed to perform a multiplicity of tasks. In some con?gurations, valve(s) 2802, PCB 2808, and other components of valve module 2800 may be overmolded together such that all of the components of module 2800 are physically attached to one another and form a single unit. In some con?gurations, module 2800 may be programmed to m basic functions (e.g. coordinating the opening and closing of inlet and outlet valves while driving a pump, regulating the ?ow or pumping rate of the pump, detecting aberrant ?ow conditions, etc), but may be automatically assigned more speci?c or ed tasks upon connection of module 2800 to a communications control bus, such as a controller area network (‘CAN’) bus.
] Referring now to D, each module 2800 may be con?gured such that it may be connectable to another module 2800, allowing assembly of manifold 2850 con?gured for a particular application. Valve modules 2800 may be arranged such that ?uid pathways of each module 2800 may be connectable or coupleable to ?uid pathways of r module 2800. End blocks 2806 may be placed on the ends of manifold 2850 to allow assembled manifold 2850 to ace with other ents such as a pressure oir or bus of a device, and onic communication bus of a device, and/or a power bus of a device. An , gasket, and/or seal may be provided to ensure integrity of the ?uid paths within ld 2850.
Continuing to refer to D, the electronic components of each connected module 2800 may be placed into communication with one another, allowing connected modules 2800 to utilize power from a single source, for example, but not limited to, a device power bus. Connected modules 2800 can share and/or synchronize data such as, for example, valve state and pressure data. Modules 2800 that include various types of electronic components can operably communicate with each other and with controllers and other devices using any communication scheme, ing, but not limited to, a CANbus. Each module 2800 may include a component (not shown) such as, for example, but not limited to, a resistor that can terminate manifold 2850 if module 2800 is located at a terminating position such as, for example, but not limited to, at the end of manifold 2850 and/or at the end of the s communications chain.
] Continuing to still further refer to D, manifold 2850 may communicate with other components of a device wirelessly or via wired connection to a device communication bus. In some con?gurations, manifold 2850 can be controlled remotely or wirelessly, and communications among modules 2800 can be Wireless. In some con?gurations, each valve module 2800 may be red to perform a full set of valve-related tasks or applications, but without a preset assigned functionality. Tasks may include, but are not limited to, synchronization of inter—modular operations, functioning as a master device of modules 2800 for multi-module ld 2850, functioning as a pumping device of modules 2800 by supplying pressure to a pneumatically or hydraulically driven ?uid pump, and/or functioning as a pneumatic or hydraulic valve controller by supplying pressure to a pneumatic/hydraulic valve interface. In some con?gurations, tasks may include, but are not limited to ing, supplying pressure to an interface for a pumping te to effect pumping of ?uid in the pumping cassette, supplying pressure to an interface for a pumping cassette to actuate valves of the pumping cassette, and/or supplying pressure to an interface for a g cassette to direct ?uid ?ow through the pumping cassette.
Continuing to refer to D, as modules 2800 are added onto manifold 2850 that carries hydraulic or pneumatic supply lines, modules 2800 may be specialized to ular tasks and/or applications. The tasks and/or applications may be automatically determined by the location of module 2800 along an interconnected chain of modules 2800 on a communications bus. Further specialization may also be imposed during ion by a system controller as required by particular applications. For example, module 2800 that can act as a pumping module may be mmed to pump at a speci?c pressure or ?ow rate. In some con?gurations, the c task assigned to a ?rst of modules 2800 may be automatically assigned to a second of modules 2800 by (1) locating the second of modules 2800 in the same position along the chain of modules 2800 on the communications bus as the ?rst of modules 2800 had been d, and/or (2) alerting a system controller to the location on the communications bus, for example, of the second of module 2800 by providing, for example, but not limited to, a unique identi?er.
Continuing to refer to D, in some con?gurations, modules 2800 may self-identify and may be assigned a unique identi?er after lation onto ld 2850.
A sor included on PCB 2808 of a master of modules 2800 may take a census of modules 2800 connected to one another in manifold 2850. Any module 2800 may be assigned as the master of modules 2800. The processor can update the census as additional modules 2800 are added to and d from manifold 2850. The processor of the master of modules 2800 may also assign one or more specialization(s) to each module 2800 in manifold 2850. The specialization ed may depend on the physical on of module 2800 on manifold 2850.
In some con?gurations, when the census of is taken, each module 2800 may be assigned a unique identi?er. The census may also determine the spatial arrangement of s 2800. For example, a processor of the master of modules 2800 may determine, during the , that a ?rst of modules 2800 is ?rst side of a second of modules and adjacent a ?rst side of a third of modules 2800. The l arrangement can aid in automatic ment of tasks to modules 2800. In some con?gurations, the spatial arrangement may be implied from identities of modules 2800.
Continuing to refer to D, in some con?gurations, modules 2800 that are added to manifold 2850 either to replace modules 2800 or add modules to manifold 2850 may automatically self-identify. For example, if a ?rst of modules 2800 needs to be ed with a second of modules 2800, the processor of the master of modules 2800 may detect when the second of modules 2800 has been installed, and may automatically assign the identity, including the tasks, of the ?rst of modules 2800 to the second of modules 2800. The second of modules 2800 may determine its own identity and tasks. The second of modules 2800 can execute commands issued for the ?rst of modules 2800, and can communicate with others of modules 2800. In some con?gurations, fault conditions may be communicated between modules 2800 within manifold 2850, and manifold 2850 can adapt to faults. In some con?gurations, a processor of a master of modules 2800 may command that ld 2850 operate in a "limp home" mode if particular fault conditions occur. For example, if manifold 2850 includes a ?rst and a second of modules 2800 and the ?rst of modules 2800 has a fault, the processor of the master of modules 2800 may command modules 2800 of manifold 2850 to continue pumping with the second of modules 2800.
Continuing to refer to D, if a communications bus of manifold 2850 has a fault and is interrupted, and if the power bus remains functional, modules 2800 of manifold 2850 may identify the fault and switch to operation in a fail safe mode. Fluid valves may, for example, be commanded to automatically close. Any other desirable fail safe mode could also be implemented. For example, module 2800 could be programmed to continue pumping of ?uid at a previously programmed or commanded flow rate. In this way, the failure of one of modules 2800 in manifold 2850 may allow the system to wind down in an y manner. For example, a blood pump module could be allowed to continue to operate for a designated period of time if a dialysate pump module were to fail in a hemodialysis system. id="p-348" id="p-348"
id="p-348"
[00348] uing to refer to D, in some configurations, modules 2800 may detect and react to various conditions. For example, in con?gurations where at least one of modules 2800 of manifold 2850 is a g module, a processor of module 2800 may detect flow condition-related information. If an abnormal ?ow ion, for example, but not limited to, reduced ?ow or no ?ow, is detected, module 2800 may arrange for and/or m troubleshooting, and/or may request that the sor of the master of modules 2800 command that troubleshooting be performed. eshooting may determine, for example, if an occlusion exists. Manifold 2850 may then cease g and signal that an error condition exists if an occlusion is detected.
Referring now to E, pneumatic system 2852 can include a number of valve modules 2800. Each module 2800 can include controller 2854 which may be included on PCB 2808 (C) of module 2800. Each module 2800 can include pneumatic block 2856. Pneumatic block 2856 may include various pneumatic components of module 2800 such as one or more valves 2802 (C), module block 2804 (C) including ?uid ?ow paths, and end block 2806 (C) if module 2800 is at the end of multi-module manifold 2850 (D). Each module 2800 may connect to various buses of a .
Data/communications bus 2864 may allow for data and/or commands to be communicated from module 2800 to module 2800 within module manifold 2850 (D) to enable synchronization and coordination of module 2800 ties in multi-module manifold 2850 (D). Commands and/or data may be conveyed to/from manifold 2950 (D) to an external board or processor via data/communications bus 2864. Power bus 2866 may supply power to modules 2800 in manifold 2850 (D). Power may pass to manifold 2850 (D) via power bus 2866 from a source external to ld 2850 (D).
Data/communication bus 2864 and power bus 2866 may be operably coupled to PCB 2808 (C). ] uing to refer to E, ?rst tic buses 2868, second pneumatic buses 2870, and third pneumatic bus 2872 may each be connected to a pressure reservoir. The pressure of the pressure reservoir can be different from the pressure of pneumatic busses 2868, 2870, 2872, Pneumatic buses 2868, 2870, 2872 may be operably coupled to end block 2806 (C) of multi-module manifold 2850 (D). Pneumatic buses 2868, 2870, 2872 may be operably coupled with pneumatic block 2856 of module 2800. The connection between module 2800 and pneumatic busses 2868, 2870, 2872 can be plug and play.
If module 2800 includes operable connection with any of pneumatic buses 2868, 2870, 2872, an identity for module 2800 may be determined and module 2800 can be ready for operation.
Continuing to refer to E, As represented by the buses of the E running through each module 2800 and on to the next, each bus may be ed through the modules 2800 of a multi—module manifold. ical power and data ication may be conveyed through a module to module connector on a PCB 2808 (see, for example, C) of each module 2800. Pneumatic buses 2868, 2870, 2872 may be conveyed through bus ?ow paths in a ?rst of pneumatic blocks 2856. The bus flow paths can align with bus ?ow paths on a second of pneumatic blocks 2856. Each module 2800 in manifold 2850 (D) may be individually ted to any of pneumatic buses 2868, 2870, 2872. In some con?gurations, pneumatic buses 2868, 2870, 2872 may be in ?uid communication with selected of modules 2800 of manifold 2850 (D). In some con?gurations, modules 2800 may have occludable ports to pneumatic block 2856, or may be constructed with a d array of ports. Controller 2854 of each module 2800 may issue valve commands 2858 to control valve(s) 2802 (C) of module 2800. Controller 2854 may receive data 2860 from one or more sensor(s) 2862 in module 2800. Sensor(s) 2862 can, for example, but not limited to, sense the pressure of ?ow paths within pneumatic block 2856. Sensor data 2860 may be used by controller 2854 to inform control of valve(s) 2802 (C). In some con?gurations, each module 2800 can identify as a pumping module, and controller 2854 may control module 2800 to cause ?uid to be pumped by pneumatic system 2852.
Continuing to refer to E, a change in volume of ?rst variable volume 2882 may cause a change in volume of second variable volume 2884. An increase in volume of ?rst variable volume 2882 may cause a corresponding se in volume of second variable volume 2884. A decrease in volume of ?rst variable volume 2882 may cause an increase in volume of second variable volume 2884. Two pneumatically driven inlet/outlet valves 2892 for second variable volume 2884 may be actuated to allow variable volumes 2882, 2884 to change in . ] uing to refer to E, ?rst variable volume 2882 and two outlet valves 2892 can be operably connected to the outputs of their respective modules 2800. Valves 2802 (C) of each module 2800 may be actuated to increase or decrease the volume of ?rst variable volume 2882. When the volume of ?rst variable volume 2882 is decreased, one inlet/outlet valve 2802 is open, and the other inlet/outlet valve 2892 is closed, ?uid will be drawn into second variable volume 2884. When the volume of ?rst variable volume 2882 is sed, one inlet/outlet valve 2892 is closed, and inlet/outlet valve 2892 is open, ?uid will be forced out of second variable volume 2884. Pumping of ?uid in either direction may be accomplished by appropriate actuation of inlet/outlet valves 2892.
Continuing to refer to E, ?rst and second variable volumes 2882, 2894 may be con?gured in any suitable arrangement which would allow a change in volume in one to be tied to a change in volume of the other. For example, ?rst le volume 2882 may surround or be surrounded by second variable volume 2884. In some con?gurations, ?rst variable volume 2882 may be separated from second variable volume 2884 by a displaceable intermediary structure which can act on second variable volume 2884 as ?rst variable volume 2882 increases or ses in volume. The intermediary structure can include, but is not limited to including, a piston, an arm, and a lever. First and second variable volume 2882, 2884 may be separated from one another by displaceable wall 2888 that can include, but is not limited to including, a diaphragm and a membrane made of a ?exible material.
Continuing to refer to E, there can be any number of le volumes, and, in some con?gurations, a change in volume of ?rst variable volume 2882 may cause a change in volume of a plurality of other variable volumes. Likewise, change in volume of a plurality of variable volumes may cause a change in volume of, for example, but not limited to, ?rst variable volume 2882. First variable volume 2882 can be de?ned by ?xed wall 2886 and displaceable wall 2888. Second variable volume 2884 can be adjacent to ?rst variable volume 2882 and can be de?ned by second ?xed wall 2889 and displaceable wall 2888. As the volume of ?rst variable volume 2882 increases, displaceable wall 2888 can be pushed toward second ?xed wall 2889. As the volume of ?rst variable volume 2882 decreases, displaceable wall 2888 can be pulled toward ?rst ?xed wall 2886.
Referring now to F, fourth pneumatic bus 2873 may be connected to a vent reservoir such as the atmosphere. Pneumatic buses 2868, 2870, 2872 may be connected to pressure reservoirs. In some con?gurations, ?rst pneumatic bus 2868 may be connected to a negative pressure reservoir, second pneumatic bus 2870 may be connected to a low ve pressure reservoir, and third pneumatic bus 2872 may be ted to a high positive re reservoir. Fourth pneumatic bus 2873 acting as a vent to the atmosphere may minimize the amount of pumping necessary to in reservoirs for buses 2868, 2870, 2872. For example, when switching a volume from ve pressure to a negative pressure or vice versa, it may be desirable to vent the volume to ambient pressure to lower the pressure difference between the volume and the reservoir. Any number of pneumatic and electrical buses may be included in various con?gurations. ing now to G, module to module connectors 2865 on data/communication bus 2864 can include cooperating pieces of hardware on each module 2800.
Connectors 2865 can create an electrical communication pathway between modules 2800.
Controller 2854 can interrupt communications between modules 2800 by toggling switch 2865A.
Communications can be interrupted when, for example, but not limited to, a manifold is self- de?ning or when a new of modules 2800 is being installed in the ld. In some rations, module 2800 may interrupt ications in a ?rst direction while maintaining communications in a second direction. Communications may be upted as a default con?guration of module 2800 upon installation into a manifold. When communication has been interrupted, in some con?gurations, a ating resistor on module 2800 may also be switched Continuing to refer to G, each message sent on the ommunication bus 2864 may be uniquely marked according to the module 2800 from which it originated. After interrupting communications, module 2800 may then poll modules 2800 on the portion of the manifold that module 2800 is still in communication with. Modules 2800 may respond to new module 2800 and new module 2800 can determine its identity or function based upon the responses received. For example, if module 2800 only receives responses from modules 1 and 2, new module 2800 can ine that it must be module 3.
Messages addressed with the unique marker for module 3 may be ed and acted upon by new module 2800. Communication with the rest of the manifold may be reestablished and next module 2800 may repeat the process to determine its identity or function, and so on. When communications are reestablished, a terminal resistor included on newly self—identi?ed module 2800 may also be switched off.
Continuing to refer to G, after module 2800 interrupts communications to one side of the manifold, module 2800 may wait for a period of time and receive messages sent across data/communication bus 2864. Module 2800 may determine its ty or function based upon the unique markers of the messages sent across the ommunication bus 2864. If new module 2800 receives messages from module 1 and 2, new module 2800 may determine that it is module 3. As above, ication with the rest of the manifold may be reestablished and this s may repeat until each module 2800 in a manifold has self-identified. A terminal resistor which may be switched in and out may be included on each module 2800. Any other process involving interruption of the communication bus to facilitate self-identification of modules 2800 in a multi-module manifold may also be used. In some con?gurations, the s may be conducted or coordinated by a master controller in the ld.
Referring now to H, a number of modules 2800 can perform a plurality of different valve-related tasks. Module 2800C can include a pumping module.
Modules 2800A and 2800B can control two-chamber ?uid pump 2896. Controllers 2854A and 2854B may operate in tandem, coordinating or synchronizing pumping operations between one another to optimize ?uid throughput and/or achieve substantially continuous pumping, for example. Controllers 2854A, 2854B, 2854C, 2854D may communicate over the data/communication bus 2864 to onize with one another. Each of controllers 2854A, 2854B may send commands 2858 to tic blocks 2856A, 2856B to effect pumping of ?uid in chambers of the ?uid pumps of modules 2800A, 2800B. In some con?gurations, controller 2854A, for example, may be synchronized to command ?lling of its associated chamber while the controller 2854B commands delivery of its associated chamber. Thus ?uid may be pumped to one of ?rst reservoir 2890 or second oir 2895 substantially uously from one of second reservoir 2895 or ?rst reservoir 2890. s 2800A, 2800B, 2800C, 2800D may coordinate to synchronize operations between a greater number of ?uid pumping chambers as well. For example, a three r ?uid pump may be controlled by modules 2800A, 2800B, 2800C that can communicate over data/communication bus 2864 to synchronize pumping.
Referring now to 1, module 2800D can be con?gured as a pneumatic (or, in some con?gurations, hydraulic) valve module that can control valves. The outputs of module 2800D can be connected to a number of ?uid valves 2897 that can control ?uid ication to various ?uid ys 2898 in the pneumatic system. Any number of ?uid valves 2897 can be included. Depending on the number of valves included in module 2800, the number of ?uid valves 2897 that module 2800D can control independently can depend on the number of valves in module 2800. System can include modules 2800A, 2800B, 2800C, 2800D that can perform a plurality of exemplary valve related tasks including ?uid pumping and ion of pneumatic ?uid valve 2897. Modules 2800A, 2800B can cooperatively control ?uid pump 2882A. For example, module 2800A may provide ?uid at a ?rst negative pressure and a second negative pressure while module 2800B may e ?uid at a ?rst positive re and a second positive pressure. Module 2800A can control the state of inlet/outlet valves 2892A, 2892B of the second variable volume 2884 of ?uid pump 2882A. Module 2800A can control a pressure input to ?rst variable volume 2882 of ?uid pump 2882A. Module 2800B can control another pressure input to ?rst variable volume 2882 as well as inlet/outlet valve 2892C of second variable volume 2884. To coordinate pumping operations for the ?uid pump, processor 2854 of modules 2800A, 2800B may synchronize valve activity related to ?uid pump 2882A over data/communication bus 2864. Synchronization can allow a manifold assembled from modules 2800A, 2800B each including four valves 2802 (C) to run a ?uid pump requiring ?ve valves 2802 (C). Modules 2800 (C) may be d to control a wide range of components or devices, for example, but not limited to, hydraulically actuated pumps and/or valves, in which manifold valve module 2800 can make a hydraulic connection to one or more pressurized hydraulic lines in a system, using, for e, quick-connect ?ttings.
Referring now to ], module 2800 may include PCB 2808. PCB 2808 can include, but is not limited to including, processor 2854 that can be programmed to automatically command ion of one or more motors 2841. PCB 2808 may include electrical outputs to each winding of motor 2841. In some con?gurations, motor 2841 and PCB 2808 may be ed as a single package and the PCB 2808 may be overmolded onto a portion of the motor 2841. Module 2800 may automatically control operation of one or more pump 2842. PCB 2808 may include electrical outputs which can ace with pump 2842. In some con?gurations, pump 2842 and PCB 2808 may be included as a single package and PCB 2808 may be overmolded onto a portion of pump 2842. Module 2800 may be programmed to control nation of one or more light emitters 2843.
Continuing to refer to J, PCB 2808 can include controller 2854 that can be programmed to control operation of one or more electromagnets 2844 based. PCB 2808 may include an electrical output that can interface with the contacts of electromagnets 2844 to energize electromagnets 2844. Modules 2800 may automatically l operation of one or more heater elements 2845. In some con?gurations, PCB 2808 can include controller 2854 that can switch current flow h heater element 2845 on and off based upon a pre-de?ned program or commands from an external main controller. For example, the main controller may command heater element 2845 to warm a e to a temperature set point. Module 2800 may e the necessary control functions to raise the temperature of the surface to the commanded temperature set point using heater element 2845 and feedback signals from a temperature sensor.
Controller 2854 can provide analog control of heater element 2845, or digital control through, for example, ation of pulse-width-modulated current to the heater element 2845. In some con?gurations, module 2800 may control a relay making or breaking a tion n a current source and heater element 2845. This may be desirable in scenarios in which heater element 2845 is run at high voltages (e. g. mains voltage). Modules 2800 may control relays such as high speed digital s, for example, thyristors, TRIACS, or silicon controlled recti?ers.
Continuing to refer to J, PCB 2808 can ace with and/or include a variety of sensors 2840 suited for particular applications. For example, sensors 2840 may include current sensors, temperature sensors, re sensors, encoders, optical sensors, magnetic sensors, inertial sensors, or any other sensor required by an application executing on module 2800. Modules 2800 used for l of other devices or components can share power transmitted through shared power bus 2866. Modules 2800 can coordinate or synchronize operation via shared data/communication bus 2864. Coordination may be n similar and/or dissimilar devices or components. Coordination may limit and/or manage peak power loads.
Referring now to K, in some con?gurations, module 1 (and any of modules 1-17 (P)) can include, for example, four valve assemblies 2902, but any number of valve assemblies 2902 can be included. Valve assemblies 2902 can include any of a variety of types of valves including binary valves, variable , or bi-stable valves. Valve assemblies 2902 can be mounted on manifold module base or block 2904. Module block 2904 can include a number of ?uid ls or ?ow paths that can interface with the ?uid inlets and outlets of each valve assembly 2902. Module block 2904 can form a manifold for valve assembly 2902. In some con?gurations, one of the inlet ports for one or more valve assemblies 2902 can be blocked. If valve assembly 2902 includes a bi—stable valve, blocking valve assembly 2902 can allow the bi-stable valve to on as a two-way valve. Module base or block 2904 may include one or more ?ow paths that can convey pressurized ?uid (e.g. pneumatic or hydraulic) from a pressurized ?uid source line to a series of interconnected ld modules. The one or more ?ow paths can also be known as ?uid busses. Any number of modules l-l7 (P) can be concatenated or connected, for example, in series. Each of modules l-l7 (P) can have a ?uid bus connecting a pressure line inlet port 2907 on one side of the module to a pressure line outlet port 2907 on another side of the module. Modules 1-17 (P) can be connected er by standard fasteners, with inlet and outlet ports 2907 joined via s or O-rings, for e. Manifold module end blocks 2906 can be operably ted to manifold 700 (P) that can be assembled from a number of valve modules l-l7 (P). End blocks 2906 can include connection ports 2907 connecting one or more pressure line inputs or outputs 706/708/710 (P) to corresponding pressure line input or output ports 2907 of each of valve modules l-l7 (P). In some con?gurations, connection ports 2907 may enable connection to pressurized ?uidic components such as, for example, but not limited to, pneumatic lines and/or buses from one or more ve pressure sources or reservoirs, negative pressure reservoirs, a vented source or reservoir (e. g. atmosphere), or other reservoir. Any suitable connector ?tting may be orated into connection ports 2907, including, for example, but not limited to, quick-connect ?ttings. Unused of connection ports 2907 may be plugged, blocked, or otherwise sealed off. In some con?gurations, three connection ports 2907 can be included. In some con?gurations, any number of connection ports 2907 can be included.
In some con?gurations, module end blocks 2906 may ate a series or bank of connected of modules 1-17 (P), and connection ports 2907 can be closed or blocked. In some con?gurations, connection ports 2907 including end blocks 2906 that terminate ted of modules 1-17 (P) can include connections to one or more ?uid lines leading to one of end blocks 2906 forming an input block of another bank of manifolds 700 (P) in a larger manifold assembly.
Continuing to refer to K, controller board (PCB) 2035 can include capacitors 2910 that can have a capacitance suf?cient to power valves 2902 to a known or desired state in the event that power to any of modules 1-17 (FIG, 55P) is lost. If the electrical power and/or communications bus e of a device operably connected to PCB 2035 drops below a predetermined level, valve(s) 2902 may be transitioned to a pre—determined con?guration, for example, but not d to, a valve state that closes a speci?ed ?uid port or opens a ed ?uid port. The pre—determined con?guration can represent a afe con?guration for an apparatus controlled by any of modules 1-17 (P). The apparatus can include, but is not limited to including, a ?uid ?ow control device such as a pump and/or valves in a l device. Capacitors 2910 can transition valve(s) 2902 to the pre-determined con?guration if power is lost.
Referring now primarily to K, each module block 2904 may e one or more coupling features that can facilitate connecting modules 1—17 (P) together to form a bank of modules 1-17 (P) or manifold assembly 2950 (L). In some con?gurations, module blocks 2904 can include holes 2914 (L) through which a fastener (not shown) may be placed to couple module blocks 2904 together. The fastener may be any variety of fastener. A fastener may also be used to couple end blocks 2906 of manifold 2950 (L) to any of valve modules 1—17 (P). Where various ?uid pathways between valves 2902, module blocks 2904, and/or end blocks 2906 interface with one another, a sealing member such as an o-ring, gasket, or the like may be used to ensure leak-free connections. In some con?gurations, module bases or blocks 2904 can be ly con?gured side—to—side, aligning pressure line input ports (not shown) and pressure line output ports (not shown) of adjacent of blocks 2904. Blocks 2904 can be fastened together using, for example, but not limited to, gaskets and/or O-rings to form a seal between the input and output ports (not shown).
One or more valve lies 2902 can be installed in each of modules 1-17 (P), either before or after s 1-17 (P) are concatenated. Valve assemblies 2902 can be positioned in le communication with receiving stations (not shown) on manifold base or block 2904. Inlets (not shown) of valve assemblies 2902 can be d with pressure ports (not shown) that can enable communication with a ?uidic re bus in module block 2904. Outlet (not shown) of each valve assembly 2902 can be aligned with a port (not shown) on module block 2906 that can enable ?uid ication with an outlet of module block 2904. A gasket can be interposed between a face of valve assembly 2902 and a mating receiving face of module block 2904. In some rations, the gasket can include a variable number of ports. In some con?gurations, module blocks 2904 can be onnected, valve assemblies 2902 can be installed, and PCB 2035 can be mounted on each of s 1-17 (F) and valve assemblies 2902. In some con?gurations, each PCB 2035 can be installed on module block 2906 before any of modules 1-17 (P) are interconnected, forming an expandable assemblage 2950 having standardized ?uidic and electronic inputs, outputs, valve mating dimensions and r of PCBs 2035.
Referring now to L, a series of interconnected (or bank) of manifold modules 1,2 can include interconnected PCBs 2035 through connector 2912 that can enable data and/or power communications and/or power bus n modules 1,2. Each of manifold modules 1,2 can be assigned a speci?c task or set of tasks, and/or PCBs 2035 can establish a ‘master—slave’ or primary—secondary hierarchical relationship. Through the transmission of identifying data to or from each PCB 203 5, any or all of the PCBs 2035 can detect the presence of and/or function of any other module 1,2 in the bank or in an entire ld assembly 2950. If a controlled device has a plurality of functions or plurality of pump/valve combinations, a y PCB 2035 can be assigned, which can then coordinate or synchronize the functions of a group of secondary modules 1,2 with respect to the controlled device. In some con?gurations, a linked group of modules 1,2 can include a subset of manifold modules 1-17 (P) in a bank or manifold assembly 2950. id="p-369" id="p-369"
id="p-369"
[00369] Referring now to M, PCB 2035 can include components such as, for example, but not limited to, ?eld programmable gate arrays, microprocessor chips, and/or a combination thereof. The components are can provide, for example, but not limited to, pressure data from on-board pressure sensors 2918 connectable to ports 2916 providing an interface with valve cavities 2902A (K) of valve assemblies 2902 (K). Pressure sensors 2918 can be aligned with pressure sensing ports or wells 2916 on module block 2904. Pressure sensors 2918 can communicate with the cavity (not shown) of valve assembly 2902. If electromagnetic coils are mounted on valve assembly 2902, electrodes on PCB 2035 can be aligned with corresponding receptacles or odes connected to the coils. Valve assemblies 2902 can be securely fastened to module block 2904, and PCB 2035 can be ly fastened to module block 2904 using fasteners, for example, but not limited to, screws. In some con?gurations, each of s 1-17 (P) can have four valve receiving stations 2916 onto which PCB 2035 can position four pressure sensors 2918 — one for each installed valve assembly 2902. Each of modules 1-17 (P) can have a fewer or greater number of receiving stations.
Continuing to refer to M, each of sensing wells 2916 can be in ?uid communication with the interior valve cavity (not shown) of one of valves 2902. Sensing wells 2916 can enable pressure sensors 2918 on PCB 2035 to sense the pressure of the interior cavity (not shown) of valves 2902. The valve cavity pressure may be measured periodically or monitored in real time, acquired and stored by PCB 203 5, and/or used by PCB 2035 to control valves 2902. Valves 2902 can be directed to perform tasks such as, for example, but not d to, selected delivery of one or another pressurized ?uid (e. g. air) to a device, such as a pump and/or valve. If valve 2902 controls a single pressure line, or if valve 2902 can simultaneously block more than one pressure line, PCB 2305 can receive pressure data that can represent the pressure present in a , for example, the valve cavity (not shown) can be in ?uid communication with a control chamber, for e, of a controlled membrane pump. Any of valve modules 1-17 (P) can be assigned the task of a pumping module. In some con?gurations, the pressure data can be used to determine, among other things, an amount of liquid transferred and a ?ow rate of the liquid being transferred in the liquid ?ow control apparatus.
Referring now primarily to N, four-valve manifold modules 1—17 (P) can function independently to operate a single pump. For example, a liquid inlet valve and outlet valve of the pump can each be assigned and ted to the output of a separate manifold valve assembly 2902 (K), which can toggle between a positive ?uidic pressure bus and negative ?uidic pressure bus in any of modules 1-17 (P) to either close or open the inlet/outlet pump valve. Third manifold valve 2902 (K) can be arranged to toggle on or off a tion of the positive pressure bus to the pump control chamber to perform a pump deliver stroke, and fourth manifold valve 2902 (K) can be arranged to toggle on or off a connection of the negative pressure bus to the pump control r to perform a pump ?ll stroke. The pump l ld valves can be converted to two-way valves (on/off) by installing them on module block 2904 (K) using a gasket having no port to the positive pressure bus if used as a ?ll l valve, or having no port to the negative pressure bus if used as a deliver control valve. PCB 2035 (M) can operate the liquid pump/valve unit by coordinating the inlet and outlet pump valves to permit ?lling the pump chamber with liquid and then expelling the liquid from the pump chamber in the direction assigned by PCB 2035 (M). PCB 2035 (M) can receive pressure data from the pump control chamber to determine rate of ?uid volume movement and end—of—stroke conditions. PCB 2035 (M) can vary the rate or amount of pressure delivered to the pump control chamber. PCB 2035 (M) can receive command sets locally from other manifold modules PCB 2035 (M), or from an external main or system controller.
Continuing to refer to N, module 1 can include output ports 2955 that can enable tubing to be connected to module 1. The tubing can supply a conduit to a destination for outputs from module 1. In some con?gurations, the destination may be, for example, but not d to, a ?uid pump, a pneumatic valve, and/or a ?uid reservoir. Any le connector ?tting may be included as part of output ports 2955. Unused output ports 2955 can be plugged, blocked, or ise sealed off.
Referring now to 0, assemblage 2950 of modules l-l7 (P) may be stacked to allow input end blocks 2906 (K) to be interconnected to supply each bank of modules 1-17 (P) with one or more pressurized ?uid lines. tion ports 2907 (K) of end blocks 2906 (K) can be sealed closed or blocked. PCB 2035 can include connectors 2912 that can operably connect PCB 2035 with additional PCBs 2035 to interconnect, for example, but not limited to, valve modules 1-4 into manifold 2950 that can be of any size or complexity. Connectors 2912 can enable communications and/or electrical power buses to be assembled in a bank, such as, for example, modules 1—4. Connectors 2912 can enable electronic communication (power and/or data) between valve modules 1-4 in manifold ly 2950 and, for example, but not limited to, an external (e.g. main or system) controller (not shown) included in a device in which manifold assembly 2950 can be led. Banks of modules 1-4 can be placed on a number of individual module racks or frames 2970. In some rations, each the banks can include four modules 1-4, though racks or frames 2970 may hold any number of modules 1—4. Each rack 2970 may include mating or coupling features (not shown) that can allow a ?rst of racks 2970 to be stacked upon a second of racks 2970, g a rack or frame assembly. For e, a ?rst side of each rack 2970 may include a pin or projection (not shown). A second side of each rack 2970 opposite the ?rst side may include a receiving structure (not shown) that can retain the projection from the ?rst side of an adjacent rack 2970 ting two of racks 2970 together. Cap 2972 can optionally top a terminal of racks 2970. Each rack 2970 may include tracks 2974 or a frame in which modules 1-4 may be retained. Tracks 2974 may enable modules 1-4 to be slid in and out of rack 2970. In some con?gurations, tracks 2974 can ensure that modules 1—4 are installed at a pre—determined orientation. Tracks 2974 may aid in alignment of connectors 2912. In some con?gurations, end blocks 2906 031G. 55K) can form at least part of the supporting structure of rack or frame 2970.
Track 2974 can accommodate any number of manifold modules 1-4 in a bank, each module 1-4 having a slot in rack or frame 2970. Modules 1-4 can be enated in a bank by mating the pressure line inlet port (not shown) of one of modules 1-4 with pressure line outlet port (not shown) of another of modules 1-4 to form ?uidic pressure bus. Modules 1—4 can be concatenated in a bank interconnecting PCBs 2035 with connectors 2912. Manifold ly 2950 formed from a stack of modules 1—4 can be modi?ed to accommodate any number or combination of ld modules 1—4.
Continuing to refer to 0, communications/power bus extension line 2913 may extend between s 1-4 on one of racks 2970 to s 1-4 on another of racks 2970. In some con?gurations, communications/ power bus extension line 2913 may be integrated into each of racks 2970. Pneumatic (or in other systems, hydraulic) communication between modules 1-4 on different of racks 2970 may be established with tic distribution lines housed or integrated within each of racks 2970. As racks 2970 are stacked, ?uidic (e. g. pneumatic) communication from a ?rst of racks 2970 to a second of racks 2970 may be automatically established. The tions may be made, for example, by press-?t plug/receptacle pairs (not shown) having leak-proof contact surfaces such as, for example, but not limited to, elastomeric gaskets or O-rings. In some con?gurations, pneumatic lines may run individually to each rack 2970. id="p-375" id="p-375"
id="p-375"
[00375] Referring now to P, manifold 700 can include, but is not limited to including, a number of s 1-17. Manifold 700 can be arranged to control operation of a ?uid circuit including a number of cassettes 282A—C (FIGS. 55R—55T). Each of modules 1—17 (P) may be substantially identical. In some con?gurations, each module 1-17 (P) may e substantially the same electronic control board 2908 (K) for processor 2038 (P) associated with each of modules 1-17. Each of modules 1-17 (P) can e pneumatic block 2025 (P) described, for example, but not limited to, herein. In some con?gurations, each pneumatic block 2025 (P) can include four valve assemblies 2902 (K), that can be labeled, for e, valves ‘n’.l-‘n’.4 (S) and accompanying outlet ports ‘n’. lV-‘n’.4V (P), where ‘n’ follows the naming convention of valve modules 1—17. In some con?gurations, any number of valve assemblies 2902 (K) per pneumatic block 2025 (P), and any number of modules l-l7 (P), may be included. The portion of cassettes 282A-C (FIGS. T) controlled by a particular port on manifold 700 is labeled correspondingly. For example, a fluid valve controlled by port "n".2V on module l-l7 can include the label "n".2 on te 282A-C (FIGS. 55R-55T).
] Referring again to P, power bus 702 and communication bus 704 can extend from module 1 to module 17 throughout manifold 700. In some con?gurations, communications bus 704 can be, but is not d to being, CAN-bus compatible. If communication is disrupted between one of modules 1—17 and others of s 1—17, power bus 702 may remain intact so that all s 1-17 have the opportunity to remain operational.
Modules 1—17 may enter an autonomous mode of operation, for example, but not limited to, upon loss of communications. For example, certain modules 1-17 along manifold 700 may enter an autonomous mode of operation (e.g. for a designated period of time) upon loss of communications so that a pump, for example, may ue to operate when an am module 1-17 fails or is disconnected.
Continuing to refer primarily to P, negative 706, high positive 708, and low positive pressure 710 pneumatic buses can extend from module 1 to module 17 throughout manifold 700. In some con?gurations, there may be a negative pressure pneumatic bus and a positive pressure pneumatic bus. Each module 1—17 can include processor 2038 which can command pneumatic block 2025 of module 1-17 and may send signals to actuate the valves of the respective module 1-17. Additionally, each processor 2038 can receive pressure data from re sensors 2027 () monitoring ?uid ?ow paths in pneumatic block 2025, so that, for example, the pressure of the pumping chambers of each cassette 282A-C (FIGS. 55R- SST) can be monitored by processors 2038. Each module 1—17 may be assigned a role depending on the portion(s) of a ?uid circuit in communication with its outlet ports ‘n’.1V-‘n’.4V. In some con?gurations, modules 1-17 can be assigned roles as, for example, but not limited to, ?uid valve control modules and pump chamber modules. Fluid valve control modules may supply positive and negative pressure to sheeting over ?uid valves of a cassette 282A-C (FIGS. 55R-55T). ve pressure may be supplied to close the valves while ve pressure may be supplied to open the valves. The pump chamber modules may control the inlet and outlet ?uid valves to pump chambers of a cassette 282A-C (FIGS. 55R-55T). The pump chamber modules may also l the application of pressure to sheeting over pump chambers to cause ?uid to be pumped by cassette 282A-C (FIGS. 55R-55T). Other role assignments are possible. The role assignments for s 1-17 and module ports can vary . In some con?gurations, if all of modules 1-17 are substantially identical, any module 1-17 may be assigned any role and may be installed in ld 700 in any order. In some con?gurations, when modules 1-17 are connected to pneumatic lines, modules 1-l7 may automatically control operation of, for e, but not d to, ?uid handling set 280 (). In some con?gurations, pump chambers may, for e, be paired with a corresponding pump chamber module. Any number of ?uid valve control modules which are dedicated to speci?c cassettes 282A—C (FIGS. 55R—55T) may be present. Any number of support modules may be included.
Referring now to Q, method 3160 can assign roles to modules 1—17 (P) in manifold assembly 700 (FIG, 55P). In some con?gurations, various modules 1-17 (F) can take on different roles from each other and perform tasks associated with those roles. In some con?gurations, the tasks may be pre-programmed onto a master module controller and can execute ndent from a main controller. In some con?gurations, a main controller can take more of an active role in controlling modules 1-17 (P). Method 3160 can include sending 3162, by the main controller, a query to the master module controller requesting the number of modules operably connected, through, for example, but not limited to, the communications bus. Method 3160 can include sending 3164, by the master module ller, a response ting the number of s operably connected, h, for example, but not limited to, the communications bus. Method 3160 can include comparing 3166, by the main controller, the number of modules speci?ed by the master controller to an expected number of modules. If 3168 the expected number of modules 1-17 (P) is greater than the number reported by the master module controller, method 3160 can include entering 3170, by the main controller, an error state. In the error state, a noti?cation for display on a user interface can optionally be displayed. In some rations, the main controller may enter an error state if the number of s 1-17 (P) reported by the master module controller differs from the expected number. For example, an error state may be entered and a noti?cation generated if the master module controller tes that extra of modules 1—17 (P) are t.
Continuing to refer to Q, if 3 168 the expected number of modules 1-17 (P) s the number reported by the master module controller, method 3160 can include determining 3172, the main controller, at least one role for a ?rst of modules 1—17 ( 55P). Method 3160 can e sending 3174, by the main controller the at least one role to the ?rst of modules 1-17 (P). Method 3160 can include con?guring 3176, by the ?rst of modules 1-17 (P), upon receipt of the at least one role, the ?rst of modules 1-17 (P) according to the at least one role. If 3 178 there are no further of modules 1-17 (P), method 3160 can terminate If 3178 there are additional of modules 1-17 (FIG‘ 55P), method 3160 can include ining 3180, by the main controller, at least one role for another of modules 1-17 (P). Method 3160 can include sending 3182, by the main controller, the at least one role to another of modules 1—17 (P). Method 3160 can include con?guring 3184, by module controller, upon receipt of the at least one task, another of modules 1-17 (P) according to the at least one role. If 3 178 there are no further modules 1-17 (P), method 3160 can terminate. If 3 178 there are additional of s 1-17 (P), method 3160 can repeat steps 3180, 3182 and 3184 all of modules 1-17 (P) have been assigned at least one role.
Continuing to refer to Q, the at least one role generated by the main controller may, in some con?gurations, include the role of a pump chamber module or a ?uid valve module, or a combination of the two. The con?gurations that could include, for example, pump chamber modules, can include con?gurations in which s 1-17 (P) control pneumatic pathways leading to a pumping cassette. In some con?gurations, the module controller can tically interpret the at least one role, and can set up valve con?gurations, sequencing and default states ing the at least one role. In some con?gurations, the at least one role may include specifying valve con?guration information to one of modules 1-17 (P). In some con?gurations, the at least one role can include specifying con?guration settings for individual valves of one of modules l—l7 (P). In some rations, the at least one role can include specifying a module number, a valve number (e.g. 1—4), and con?guration setting. Each of modules l-17 (P) may be red to accept a plurality of valve assemblies 2902 (K). In some con?gurations, the number of valve assemblies 2902 (K) per module l-l7 (P) can be standardized to permit ready replacement or substitution of valve assembly 2902 (K) and gasket at an assigned location in one of modules l-l7 (P), or ready replacement of the entire of one of s 1-17 (P) without necessitating re-programming of the module controller. In some con?gurations, the gasket mating valve assembly 2902 (K) to the ?uidic bus (pneumatic or hydraulic) may have different communication holes or ports to the bus to permit or deny access of the valve to a particular re line in the bus. Possible con?guration settings can include, but are not limited to including, the setting in TABLE X.
Valve Con?-urations Fluid Valve 3-way valve with an input connected to positive pressure and an in ut ted to neative ressure Chamber Valve Pos 2-wa valve with an in out connected to ositive ressure Chamber Valve Ne; 2-wa valve with an in ut connected to ve ressure source .ressure to an accumulator .ressure reference volume and a control chamber blocked off TABLE X ] Continuing to refer to Q, in some con?gurations, each of modules 1—17 (P) may default to predetermined valve con?guration settings. In some con?gurations, the main controller may not generate a role for a module if the t settings are provide the desired tasks. In some con?gurations, each of modules l-17 (P) may default to a pump chamber control module con?guration in Which two valves of the module are red as ?uid valves, one is con?gured as a positive chamber valve, and another is con?gured as a negative chamber valve. In some con?gurations, roles may e primary or grouped tasks addressed to a master module controller Any of the module controllers in a manifold assembly may be assigned to be a master module controller. The master module controller can receive a primary role assignment from a main or system controller via the communications bus. The primary or grouped role may include the task of assigning a role to a master module to nate the tasks of a speci?c secondary module or group of secondary modules. In some con?gurations, the primary or grouped role may include tasks that specify that the master module controller coordinates or synchronizes pumping performed by two or more pump chamber modules (e. g. pump chamber modules controlling two or more pump chambers of the same device or the same pump cassette). This may cause the speci?ed secondary modules to effectively operate in tandem to provide the pumping device with greater potential throughput.
In some con?gurations, the main ller can transmit a single role and/or at least one task with a group identi?er. The master module controller of the primary module can receive the role and/or at least one task and transmit the role and/or at least one task to ary modules associated with the group identi?er. Although timing of inlet and outlet pump valve operations with an associated pump operation can be performed y with the on-board controller of the individual pump control modules, synchronizing the operation of one pump/valve combination with another pump/valve combination may be a function of the group role and/or at least one task coordinated by the master module controller. The module controller can include software, ?rmware, and/or hardware led on any of the on—board controllers of the valved ld modules. In some con?gurations, a master module ller may be omitted. In some con?gurations, a controller al to the manifold assembly, such as a main or system controller, may m the functions of the master module controller.
Continuing to still further refer to Q, a role can include tasks that specify that the master module controller coordinate operations of a pump chamber module with a volume measurement module, for e, but not limited to, a manifold module having a valved connection to a reference chamber and to vent for pressure/volume calculations. This may cause the master module ller to synchronize operations of the volume measurement module with the pump r module so that the volume measurement module performs a pressure ement to determine the volume transferred in each pump stroke commanded by the pump chamber module.
Referring now primarily to R, in some con?gurations, s 1- 17 (P) may also be assigned roles which support or supplement the roles of other modules 1-17 (P). For example, some modules 1-17 (P) may act to vent components of a ?uid t. The control chamber for a pump chamber, may, for example, be vented in various stances. Additionally, some support modules 1—17 (P) may be measurement modules which measure the volume of ?uid which is transferred during pumping.
Other support modules are also possible, for example some modules or module ports may play a support role in which pressures of various portions of a ?uid circuit or pneumatic circuit are sensed by the module. In some con?gurations, module 15 (P) may optionally be a regulator module which regulates the pressure fed to modules 16, 17 (P) disposed downstream. Ports 16.3V and 16.4V (P) may be associated with pneumatic isolation assembly 4600 (W) instead of a valve such that the ports 16.3V, 16.4V (P) may be used for sensing pressure, for example. Pneumatic isolation assembly 4600 (W) may seal off a volume of the module in which a pressure sensor in communication with the associated port is located.
Continuing to refer to R, in some con?gurations, ports 16.3V, 16.4V (P) can be connected at 16.3 and 16.4 to level sensing lines 296A, 296B of storages oirs 182A, 182B. Pressure sensors associated with the ports 16.3V, 16.4V (P) can monitor the pressure in the level sensing lines 296A, 296B. The sensed pressure of the level sensing lines 296A, 296B may be used to determine the level or volume of a ?uid contained within the storage reservoir 182A, 182B. Ports 17.1V and 17.2V (P) can be associated with pneumatic ion assembly 4600 (W) and can be used for g pressure. In some con?gurations, ports 17.1V, 17.2V (P) may be connected at 17.1 and 17.2 to atmosphere or ambient pressure 720. The pressure sensors associated with ports 17.1V, 17.2V (P) may monitor t pressure 720 and generate a pressure offset value. The pressure offset value may be used when determining re from pressure data provided by other pressure sensors in a manifold 700 (P). The pressure offset value may be ed based on a prede?ned le as ambient pressure values may te throughout a day.
Continuing to refer to R, in some con?gurations, ports 17.1V and 17.2V (P) can be connected to ambient pressure 720 to provide ancy. The pressure data or pressure offset values generated from the pressure sensors ated with each port 17.1V, 17.2V (P) may be compared t one another to ensure they are within a prede?ned range of each other. If the values are not within the prede?ned range of one another, an error state may be entered and a noti?cation may be generated. In some con?gurations, only one port 17.1V, 17.2V (P) may be arranged to r atmospheric pressure and generate a pressure offset value. Port 13.4V (P) may be ted to ?uid valve 13.4 which may be included in stand-alone valve block 730. Stand alone valve block 730 may e ?uid ?ow body 732 separated by displaceable sheet or barrier 735 from pneumatic chamber body 734.
Pneumatic chamber body 734 may include control volume 736 to which pressure from port 13.4V (P) may be supplied. The pressure may cause displacement of displaceable barrier 735 to open and close valve port 738 of stand-alone valve block 730. Fluid ?ow body 732 may include material that can include inlet ?ow path 740 and outlet ?ow path 742. Communication between inlet ?ow path 740 and outlet ?ow path 742 may be interrupted as displaceable barrier 735 is displaced against valve port 738 to outlet ?ow path 742. Positive pressure may be supplied to pneumatic control chamber 736 to displace barrier 735 against valve port 738 to close the valve. Negative pressure may be supplied to pneumatic control chamber 736 to displace barrier 735 away from valve port 738 to open the valve. Fluid lines may be coupled to inlet ?ow path 740 and outlet ?ow path 742 with any of a variety of ?ttings or connectors. Inlet ?ow path 740 and outlet ?ow path 742 may be associated with, for example, but not limited to, barbed connectors, luer-locks, and/or quick ts to facilitate connection to ?uid lines. uing to refer to R, ?uid ?ow body 732 and pneumatic chamber body 734 may be coupled to one another in any suitable manner. For example, ?uid ?ow body 732 and pneumatic chamber body 734 may be ultrasonically welded to one another with ?exible barrier 735 ed in between. In some con?gurations, ?uid ?ow body 732 and pneumatic chamber body 734 may be coupled together with fasteners. In some rations, a gasket member may be included to provide a ?uid tight seal. le barrier 735 may be integral to the gasket member in some con?gurations. Stand-alone valve block 730 may be incorporated into any ?uid line of a ?uid circuit and may allow for ?ow through that line to be affectively occluded. In some con?gurations, at least one stand alone valve body 730 may be incorporated into ?uid handling set 280 (). In some rations, stand-alone valve body 730 may be ed to a ?uid line such as ?uid line 284 () which can act as an inlet line to ?uid handling set 280 (). Stand-alone valve block 730 may be replaced by a solenoid performing the same on.
] Referring now to FIG. SSS, a portion of a manifold can include regulator module 4502 that can regulate the pressure of a pneumatic bus to a second or regulated pressure which is different from that of the pneumatic bus. Regulator module 4502 can include a valve (not shown) in pneumatic block 2856 of regulator module 4502 that can separate the pressure bus from a separate chamber or an accumulator 4508, 4510. The valve (not shown) can be toggled to te the pressure. The pressure of accumulator 4508, 4510 may be sensed by a pressure sensor (not shown) that can be monitored by controller 2854 of regulator module 4502.
Controller 2854 may toggle the valve (not shown) using data from the re sensor (not shown). In some con?gurations, ller 2854 may command the valve (not shown) to toggle to place accumulator 4508, 4510 in communication with the pressure bus when the sensed pressure of accumulator 4508, 4510 falls below a ?rst predetermined value. Controller 2854 may command that the valve close off communication between the pressure bus and accumulator 4508, 4510 when the sensed pressure of accumulator 4508, 4510 is above a second predetermined value. In some con?gurations, regulator module 4502 can operably icate with ve pressure bus 4504 and negative pressure bus 4506. Regulator module 4502 may regulate the pressure of positive pressure bus 4504 to a lower positive pressure. Regulator module 4502 may regulate the pressure of negative pressure bus 4506 to a weaker negative pressure. In some con?gurations, ports 4502-1 and 4502-3 of regulator module 4502 can operably icate with positive pressure accumulator 4508. Ports 4502—2 and 4502-4 of tor module 4502 can operably communicate with negative pressure accumulator 45 10. id="p-388" id="p-388"
id="p-388"
[00388] Continuing to refer to S, accumulators 4508, 4510 may include any reservoir. In some con?gurations, accumulators 4508, 4510 may be cal.
Accumulators 4508, 4510 may, for example, include c and/or metal tanks and may have an interior volume between 500ml and 2L. Port 4502-3 may be an outlet port for a valve of pneumatic block 2856 controlling ?uid communication between positive pressure bus 4504 and positive pressure accumulator 4805. Port 4502—4 may be an outlet port for a valve of pneumatic block 2856 controlling ?uid communication between negative pressure bus 4506 and negative pressure accumulator 4510. The valves associated with ports 4502-3 and 4502-4 may be toggled by ller 2854 based on the sensed pressure of their respective accumulators 4508, 4510. In some con?gurations, pneumatic block 2856 may include pneumatic isolation members or assemblies 4600 (W) that can be associated with ports 4502-1, 4502-2. Ports 4502-1, 4502-2 may be ted to a ?uid volume such that the pressure s associated with ports 4502-1, 4502—2 may monitor the re of the ?uid volume. In some rations, port 4502— 1 can be operably connected to negative pressure accumulator 4510 to periodically measure or monitor the pressure of negative pressure accumulator. Port 4502-2 can be operably connected to ve pressure accumulator 4508 to periodically measure or monitor the pressure of positive pressure accumulator 4508. Modules 4512 of manifold 4500 may draw from pressure accumulators 4508, 4510 and operate at the regulated pressure of accumulators 4508, 4510. In some con?gurations, if the ?uid circuit includes at least one ?uid handling te, the ?uid valves of the te may be operated at greater res than the pump chambers of the cassette. Pump chambers of a cassette, or of a number of different cassettes in a ?uid circuit, may be operated at different res. Modules 4512 controlling portions of the ?uid circuit which operate at certain pressures may be disposed upstream of regulator module 4502 and modules 4512 which operate at other pressures may be disposed downstream of regulator module 4502. In some con?gurations, a plurality of regulator modules 4502 can enable a ?uid circuit to be operated at more than two sets of pressures. id="p-389" id="p-389"
id="p-389"
[00389] Referring now to FIG. SST, tic isolation assembly 4600 can be included in pneumatic block 2856 (V) of a module, for example, regulator module 4502 (V). Pneumatic ion ly 4600 may isolate a pressure bus or buses communicating with, for example, but not limited to, regulator module 4502 (V) from the port with which pneumatic isolation assembly 4600 is associated. Pneumatic isolation assembly 4600 may be associated with a port of, for example, but not limited to, regulator module 4502 (V) if the port is used, for example, for sensing purposes. In some con?gurations, pneumatic ion assembly 4600 can include a modi?ed ?uid valve. tic ion assembly 4600 can include gasket member 4602 that can block and/or isolate pressure buses feeding into pneumatic isolation assembly 4600 from the module port associated with pneumatic isolation ly 4600. In some con?gurations, pneumatic isolation assembly 4600 can include any suitable means of isolating the pneumatic buses from a module port. In some rations, a block of gasketing material may be attached to a module in place of, for example, a valve. Plugs or a similar structure may be coupled into the module or a ?xative or glue may be used to seal off pneumatic ports. Pneumatic isolation assembly 4600 may be con?gured in many ways, including, but not limited to, omitting coil assemblies 4650.
Pneumatic ion assembly 4600 may be constructed from various materials, the choice of als being unconstrained by magnetic ?ux paths which are not a n in pneumatic isolation assembly 4600. In some con?gurations, fasteners 4644 may be omitted when, for example, pneumatic isolation assembly 4600 includes a single block of material or a number of pieces of material which may be, for e, but not limited to, snap ?t, friction ?t, and/or solvent bonded together.
Referring now to , method 150 for manufacturing an enclosure can include, but is not limited to including, creating 151 a ?uid/liquid-tight seal between a ?rst face of an adapter and a ?rst section of the enclosure, the ?rst n having a ?rst side, and a second side. The method 150 may include penetrating 153 the ?rst section to create at least one ure pass-through. The method 150 may include coupling 155 an end of a ?rst ?uid line to the adapter. The method 150 may e placing 157 an end of a second ?uid line disposed on an opposing side of the adapter into ?uid communication with the ?rst ?uid line, the opposing side being opposite the ?rst face, a closed ?uid path being formed between the end of the ?rst ?uid line and the end of the second ?uid line. The method 150 may also include creating 159 a ?uid/liquid-tight seal between at least a portion of a second section of the enclosure and at least a portion of the ?rst section.
Referring now to , method 250 for using an enclosure can e, but is not limited to including, creating 251 a ?uid/liquid—tight seal between a ?rst face of an adapter and a ?rst section of the enclosure, the ?rst section having a ?rst side, and a second side.
The method 250 may include penetrating 253 the ?rst n in at least one location, each of the at least one location aligned with at least one line ?tting extending from the ?rst face of the adapter. The method 250 may include coupling 255 at least one ?rst ?uid line to each of the at least one line ?tting ing from the ?rst face. The method 250 may include coupling 257 at least one second ?uid line to each of at least one ng line ?tting extending from an opposing adapter face opposite the ?rst face. The method 250 may include creating 259 a ?uid/liquid—tight seal n a portion of a second section of the enclosure and a portion of the ?rst section. The method 250 may include inserting 261 a biological specimen between the ?rst section and the second section. The method 250 may include placing 263 the biological specimen in ?uid communication with at least one of either the at least one ?rst and second ?uid line. The method 250 may also include creating 265 a complete ?uid/liquid-tight seal between the ?rst section and the second section.
Referring now to , a method 149 for manufacturing an enclosure can include, but is not d to including, attaching 152 an adapter to a ?rst section of the enclosure. The ?rst section may have a ?rst side, a second side, and at least one edge. The attachment may create a ?uid/liquid-tight seal. The method 149 may further include penetrating 154 the ?rst section through the adapter in at least one location. The at least one location may have at least one tubing ?tting surrounding the at least one location. The tubing ?tting may be a barbed ?tting or a locking interface such as a luer lock for non-limiting example. The method 149 may further include coupling 156 at least one tube to the at least one location. The at least one tube may have a ?rst end and a second end. The ?rst end may host a ?uid t. The second end may host a ?uid conduit. In some con?gurations, the ?uid conduit in the ?rst end may be continuous with the ?uid conduit in the second end. Alternatively, the ?rst end may host a cannula and the second end may host a a. The method 149 may further include sealing 158 a second section of the enclosure to the ?rst section at least on part of the at least one edge.
] Referring now to , method 249 for manufacturing an ure can include, but is not limited to including, attaching 252 an adapter to a ?rst section of an enclosure.
The ?rst section may have a ?rst side, a second side, and at least one edge. The attachment may form a iquid—tight seal. The method 249 may further e penetrating 254 the ?rst section through the r in a plurality of locations. The plurality of locations may each have at least one tubing interface surrounding each of the plurality of locations. The tubing interface may be a barbed ?tting or a locking interface such as a luer lock for non-limiting example. The method 249 may further include ng 256 a plurality of tubes to each of the plurality of locations. The plurality of tubes may each have a ?rst end and a second end. The ?rst end may host a ?uid t and the second end may host a ?uid conduit. The ?uid conduit in the ?rst end may be continuous with the ?uid conduit in the second end. Alternatively, the ?rst end may host a cannula and the second end may host a cannula. The method 249 may further e sealing 258 a second section of the enclosure to the ?rst section at least on part of the at least one edge. The method 249 may further include inserting 260 a biological specimen between the ?rst section and the second section. The method 249 may further include placing 262 at least one of the ?uid conduits into ?uid communication with the biological specimen. This may include ucing the ?uid conduit into the biological specimen. Alternatively, the method 249 may include introducing at least one of the cannulae into the biological en. The method 249 may further include completely sealing 264 the ?rst section to the second section.
Referring now to , method 600 can be used to manufacture a ?uid pumping cassette for tissue engineering. Method 600 may e forming 602 a base including a depression having chamber walls. Optionally, forming 602 a base may include g a base with a depression having at least one limit structure or spacer disposed upon the r walls.
The method 600 may include forming 604 valves, and a number of ?uid ports. The ?uid ports may include at least one ?uid port which enables extracellular matrix isolating or recellularizing ?uid to be admitted to the cassette, a reservoir ?uid inlet, at least one waste port, and a number of ?uid loop ports. The at least one ?uid port which enables extracellular matrix isolating or recellularizing ?uid to be admitted to the cassette may be a specimen ?uid port. The method 600 may include forming 606 at least one ?uid pathway which places the depression, valves, and ?uid ports in ?uid communication with one another. This ?uid communication may be selective or interruptible ?uid communication. For example, forming 606 the at least one ?uid pathway may include forming the at least one ?uid y such that valves allow various regions of the te to be ?uidically isolated from one another if desired. The method 600 may include attaching 608 a ?exible membrane to the base. The ?exible membrane and chamber walls may de?ne a pump r. The at least one limit ure may be constructed and oned to de?ned the shape of the membrane at its greatest excursion into the depression and to create a chamber trap volume.
Still referring to , the method 600 may also include attaching ?uid conduits to each of the ?uid ports. The method 600 may include attaching a specimen ?uid t to each of at least one specimen port. The specimen ?uid conduit(s) may include a specimen ?uid conduit end which is con?gured to ace with an enclosure or tissue engineering bioreactor or alternatively with a biological specimen.
Referring now to , an example method 620 which may be used for cturing a tissue engineering set is depicted. The method 620 may include, but is not limited to including, forming 622 at least one reservoir for tissue engineering. Forming 622 at least one reservoir may e forming the at least one reservoir with an inlet and an outlet port.
The method 620 may include forming 624 a tissue engineering bioreactor sized to hold a desired biological specimen. Forming 624 the tissue engineering bioreactor may include forming the tissue engineering bioreactor with at least one ?uid port and an r. The adapter may allow for ?uid conduits to access an interior volume of the tissue ering bioreactor in which the desired ical specimen is held. The method 620 may include forming 626 a ?rst cassette including a ?rst source port in communication with a ?rst source line and at least one secondary source port in communication with at least one secondary source line. Forming 626 the ?rst cassette may e forming the ?rst cassette with a ?rst pump chamber, at least one ?uid pathway, and at least one valve managing the routing of ?uid through the ?rst cassette. Forming 626 the ?rst cassette may include forming the ?rst cassette with a reservoir port in communication with a reservoir inlet conduit coupled to an inlet port of the at least one reservoir.
The method 620 may include forming 628 a second cassette including a pump chamber, at least one ?uid pathway, and at least one valve managing routing of an extracellular matrix isolating or recellularizing ?uid through the second cassette. g 628 the second cassette may e g the second cassette with a reservoir inlet port in ication with a reservoir outlet conduit leading to an outlet port of the at least one reservoir. Forming 628 the second cassette may e forming the second cassette with a tissue engineering bioreactor interface port in communication with a bioreactor conduit leading to or into the tissue engineering bioreactor. In some con?gurations, method 620 may include forming a plurality of such second cassettes. The method 620 may include packaging 630 at least one reservoir, tissue engineering ctor, ?rst cassette, and second cassette together to form a tissue engineering ?uid ng set. id="p-397" id="p-397"
id="p-397"
[00397] Various alternatives and ations can be d by those skilled in the art without departing from the disclosure. Accordingly, the present disclosure embraces all such alternatives, modi?cations and variances. Additionally, while several con?gurations of the present disclosure have been shown in the drawings and/or sed herein, the disclosure is not limited thereto. Therefore, the above description should not be construed as limiting, but merely as exempli?cations of particular con?gurations. And, those skilled in the art will envision other modi?cations within the scope and spirit of the claims ed hereto. The present teachings are also directed to a system and methods that can be executed in hardware, ?rmware, and/or software for accomplishing the methods discussed herein, and, possibly, er readable media storing software for accomplishing these methods and system. The various modules described herein can be provided in conjunction with a single CPU, or on an arbitrary number of different CPUs. Other alternative computer platforms can be used. The operating system can be, for example, but is not limited to, WINDOWS®, , and VMS. ications links can be wired or wireless, for example, using ar communication systems, military communications systems, and satellite communications systems. Any data and results can be stored for future retrieval and processing, printed, displayed, transferred to another computer, and/or transferred elsewhere. In ance with the statute, the present teachings have been described in language more or less speci?c as to structural and methodical features. It is to be understood, however, that the present teachings are not limited to the c features shown.
Referring again to FIGS. 46A-46D, 55Q, and 56-61, methods 1500 (A), 1550 (B), 1580 (C), 1530 (D), 3160 (Q), 150 (), 250 (), 149 () 249 (), 600 (), 620 (), can be, in whole or in part, implemented electronically. Signals representing actions taken by ts of systems that implement the methods of the present con?guration, and other disclosed con?gurations can travel over at least one live communications network. Control and data information can be electronically executed and stored on at least one computer-readable medium. The system can be implemented to execute on at least one computer node in at least one live communications network enabled by such protocols as TCP/IP and PCAN, for example. Common forms of at least one computer—readable medium can include, for example, but not be limited to, a ?oppy disk, a ?exible disk, a hard disk, magnetic tape, or any other magnetic medium, a compact disk read only memory or any other optical , punched cards, paper tape, or any other physical medium with patterns of holes, a random access , a programmable read only memory, and erasable programmable read only memory (EPROM), a Flash EPROM, or any other memory chip or cartridge, or any other medium from which a computer can read. Further, the at least one computer readable medium can contain graphs in any form including, but not limited to, Graphic Interchange Format (GIF), Joint Photographic Experts Group (JPEG), Portable Network cs (PNG), Scalable Vector Graphics (SVG), and Tagged Image File Format (TIFF).
The con?gurations shown in drawings are presented only to demonstrate certain examples of the present teachings. The drawings bed are illustrative and are non- limiting. In the gs, for illustrative purposes, the size of some of the elements may not be drawn to a particular scale. Elements shown within the drawings that have the same numbers may be identical elements or may be similar elements, ing on the context.
The terms "first", "second", "third" and the like, whether used in the description or in the claims, are provided for distinguishing elements. It is to be understood that the terms so used are interchangeable under riate circumstances s clearly disclosed otherwise) and that the configurations of the disclosure described herein are capable of ion in other sequences and/or arrangements than are described or illustrated herein.
While the present teachings have been described above in terms of specific examples, it is to be understood that the present teachings are not limited to the disclosed examples. Many modifications and other es are intended to be and are covered by this disclosure and the appended claims.
Claims (12)
1. A g/mixing cassette comprising: a cassette body; a planar structure including at least one wall and a perimeter wall defined upon the cassette body; at least one valve seat surrounded by the at least one wall to define a valve well; cassette ng covering the at least one valve seat forming at least one pump chamber; at least one fluid valve; at least one fluid pathway configured to receive fluid from the at least one fluid valve, the fluid moving the cassette sheeting when re is exerted on the at least one pump chamber; at least one solution port receiving the fluid from at least one source; at least one oir port operably coupled with a fluid reservoir; and a loop out port and at least one loop return port ured to be in communication with ends of a loop line and to allow fluid to flow through the loop line from one portion of the cassette to the at least one loop return port, the at least one loop return port fluidically coupling the cassette with a medium, the cassette including the loop out port fluidically coupling the te with at least one reservoir, the cassette including at least one solution port fluidically coupling the cassette with at least one second fluid, the cassette including at least one mix pump in communication with the loop line, the cassette including at least one mix cassette valve managing the routing of the at least one second fluid from the at least one loop out port through the at least one mix pump to the at least one loop return port, the at least one mix pump mixing together a plurality of the at least one second fluid with the fluid from the at least one source.
2. The cassette as in claim 1 further comprising: at least one spike port.
3. The cassette as in claim 1 further comprising: a vent port g pressure build-up from the at least one .
4. The cassette as in claim 1 wherein the vent port comprises: a filter.
5. The pumping/mixing cassette as in claim 1 wherein the cassette body comprises: a rigid member.
6. The pumping/mixing cassette as in claim 1 wherein the cassette body comprises: a hard al.
7. The pumping/mixing cassette as in claim 1 wherein the at least one wall projects at an angle from a plane of the cassette body.
8. The pumping/mixing cassette as in claim 1 n the cassette sheeting comprises: substantially impermeable and flexible material.
9. The cassette as in claim 1 further comprising: spacers providing a dead space between the cassette sheeting and the pump chamber.
10. The pumping/mixing cassette as in claim 1 wherein the loop line comprises: at least one .
11. The pumping/mixing cassette as in claim 1 wherein the loop line comprises: at least one thermal regulating element.
12. A cassette ing to claim 1, substantially as herein described or exemplified. momw warm ’ I . ’ I .
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ780975A NZ780975A (en) | 2015-10-09 | 2016-10-07 | Fluid pumping and bioreactor system |
NZ780974A NZ780974A (en) | 2015-10-09 | 2016-10-07 | Fluid pumping and bioreactor system |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562239793P | 2015-10-09 | 2015-10-09 | |
US201562246191P | 2015-10-26 | 2015-10-26 | |
US201562266548P | 2015-12-11 | 2015-12-11 | |
NZ776411A NZ776411A (en) | 2015-10-09 | 2016-10-07 | Fluid pumping and bioreactor system |
Publications (2)
Publication Number | Publication Date |
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NZ780876A NZ780876A (en) | 2023-10-27 |
NZ780876B2 true NZ780876B2 (en) | 2024-01-30 |
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