WO2021087421A1

WO2021087421A1 - Working principles and devices for an integrated biological experimentation and research system

Info

Publication number: WO2021087421A1
Application number: PCT/US2020/058451
Authority: WO
Inventors: Xiaotian Ma; Ying Pan
Original assignee: Fibulas, Inc.
Priority date: 2019-11-02
Filing date: 2020-11-01
Publication date: 2021-05-06

Abstract

The present invention introduces a method to carry out biological experiments in a way using biological material combining metadata of said biological material as the basic processing unit. The present invention also includes the devices that are able to organize such experiments with minimum human intervention. The present invention also includes embodiments of implementation of devices carrying out the methods.

Description

Working Principles and Devices for an Integrated Biological Experimentation and Research System

FIELD OF THE TECHNOLOGY

[0001] The invention relates to the field of the automation of laboratory practice, and more particularly it relates to the automation of biological laboratory practice.

BACKGROUND OF THE TECHNOLOGY

[0002] Current laboratory practice treats specimen and the measurement results separately, which renders weakness in version control of specimen as well as the documentation of experiments. Compared to the workflow in computer science where the subject being processed by a tool and the tool are essentially equivalent (software and data are equivalent since software is data describing how to treat data), biological experiments can be organized in a similar fashion where the biological material is combined with the data containing all the process history of said biological material, which is the essence of this invention.

SUMMARY

[0003] The present invention introduces a method to carry out biological experiments in a way using biological material combining metadata of said biological material as the basic processing unit. The present invention also includes the devices that are able to organize such experiments with minimum human intervention. The present invention also includes embodiments of implementation of devices carrying out the methods.

[0004] It is to be understood that, both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0005] The system and/or method may be better understood with reference to the following figures and descriptions. Non-limiting and non-exhaustive descriptions are described with reference to the following drawings. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating principles. In the figures, like referenced numerals may refer to like parts throughout the different figures unless otherwise specified. [0006] FIG. 1 is an illustrative schematic of the system, as well as cyte and cyte files.

[0007] FIG.2 shows an illustrative example of a hypothetical workflow within the system.

[0008] FIG.3 shows the interaction of each devices within the system during the execution of the workflow in FIG.2.

[0009] FIG.4 illustrates the basic components as well as the configuration of an embodiment of cyte.

[0010] FIG.5 illustrates the basic components as well as the configuration of another embodiment of cyte.

[0011] FIG.6. illustrates an embodiment of a display of the terminal within the system.

[0012] FIG.7 illustrates the graphic experimental interface in the display shown in FIG.6.

[0013] FIG.8 illustrates an embodiment of the configuration of devices within the system.

[0014] FIG.9 is a close-up view of the central portion of the configuration shown in FIG.8.

[0015] FIG.10 is a close-up view of a GPU device of the configuration shown in FIG.8.

[0016] FIG.11 is a close-up view looking from bottom of the central portion of the configuration shown in FIG.8.

[0017] FIG.10 is a close-up overhead view showing the alignment of devices shown in

FIG.8.

[0018] Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and/or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various examples of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible example are often not depicted in order to facilitate a less obstructed view of these various examples. It will further be appreciated that certain actions and/or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above, except where different specific meanings have otherwise been set forth herein.

DETAILED DESCRIPTION OF ILLUSTRATED EXAMPLES [0019] The principles described herein may be embodied in many different forms. Not all of the depicted components may be required, however, and some implementations may include additional components. Variations in the arrangement and type of the components may be made without departing from the spirit or scope of the claims as set forth herein. Additional, different or fewer components may be provided.

[0020] Reference throughout this specification to “one example,” “an example,”

“examples,” “one embodiment,” “an embodiment,” “example embodiment,” or the like in the singular or plural means that one or more particular features, structures, or characteristics described in connection with an embodiment or an example is included in at least one embodiment or one example of the present invention. Thus, the appearances of the phrases “in one embodiment,” “in an embodiment,” “in an example embodiment,” “in one example,” “in an example,” or the like in the singular or plural in various places throughout this specification are not necessarily all referring to the same embodiment or a single embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0021] The terminology used in the description herein is for the purpose of describing particular examples only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Also, as used in the description herein and throughout the claims that follow, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise. It will also be understood that the term “and/or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will be further understood that the terms “may include,” “including,” “comprises,” and/or “comprising,” when used in this specification, specify the presence of stated features, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, operations, elements, components, and/or groups thereof.

[0022] Some terms referred in this invention may be interpreted as follows:

[0023] Protein: large biomolecules that serve multiple functions within organisms. Proteins including but not limited to enzymes, antibodies, and membrane proteins.

[0024] Cell: A basic structural, functional and biological unit of living organisms. In the following context, the terms “cell” and “cells” refer to but not limited to cells directly collected from living organisms, cells created, manipulated and replicated outside living organisms, bacteria living inside or outside living organisms, and .etc.

[0025] Tissue: an ensemble of similar cells from the same origin that carry out a specific function. A tissue may be directly acquired from a living organism, grown outside or inside a living organism from individual cells, or artificially synthesized or assembled using cells and other material.

[0026] Organ: Organs are groups of tissues with similar functions.

[0027] Biological materials: materials and organisms that form organisms or produced by organisms, primarily including virus, cells, tissues, organs, protein, and nucleic acid. Biological materials also include raw foods and its ingredients such as meat, milk, fruit, and vegetables.

[0028] Thawing: a process to unfreeze biological material.

[0029] Laboratory procedures: the scope of Laboratory procedures within this invention covers the steps that use biological materials to perform certain tasks, including but not limited to experiments, manufacturing, and medical treatments.

[0030] Medium: a mixture of chemicals to be mixed with the biological material. The composition of a medium depends on its purpose.

[0031] Protocol: In natural and social science research, a protocol is most commonly a predefined procedural method in the design and implementation of an experiment.

[0032] Culture: Cell/tissue culture is the process by which cells/tissues are grown under controlled conditions, generally outside their natural environment.

[0033] Incubator: Incubator is a device used to grow and maintain microbiological cultures or cell cultures. The incubator maintains optimal temperature, humidity and other conditions such as the CO (C02) and oxygen content of the atmosphere inside.

[0034] Integrated Biological Experimentation & Research System (IBERS): an integrated system that carries out biological experiments, measurements, and storage with minimum human intervention. If not otherwise specified, the term "the system" refers to the "Integrated Biological Experimentation & Research System".

[0035] Cyte: a basic integrated processing unit combining biological material and the information associated with the said biological material in the system.

[0036] Metadata: the said information within a cyte, and it typically includes the information regarding the biological material within the cyte, the history of processes applied to the cyte, the owner's information of the cyte, etc.

[0037] Cyte file: an ensemble of cytes grouped together based on the relation of their history or metadata. The cytes within a cyte file is optionally kept together physically, during operations applied to an entire cyte file.

[0038] Carousel: a device that holds cytes in the system. Cytes are sent from CAROUSEL to other devices in the system for operation and are sent back to CAROUSEL after the completion of the operation. Cytes is held in CAROUSEL for designated amount of time.

[0039] Central Processing Unit (CPU): a device that arranges the operations of devices within the system.

[0040] Distributor: a distribution network that transports cytes between different devices within the system.

[0041] Procedure Logic Unit (PLU): a device within the system that carries out individual experimental operations, such as adding reagents, centrifuging, coping, etc. PLUs are reconfigurable to fit different purposes.

[0042] Peripheral Storage Unit (PSU): a storage device for cyte, which potentially has larger storage capacity compared to CAROUSEL.

[0043] Graphic Processing Unit (GPU): a device within the system that performs most of the measurement for the cytes situated in CAROUSEL.

[0044] Terminal: a device interface within the system, and users interacts with the system using the terminal.

[0045] Waste Processing System (WPS): a device within the system that handles the chemical/biological waste as well as discarded cytes and cyte package containers. [0046] Port: a device within the system that handles the transportation of cytes between the system and external devices.

[0047] Local Area Nexus (LAN) : a transportation network connecting the Ports of different

IBERS, comprising a cable system transferring metadata, a conveyor system transporting cyte packages, one or multiple node to redirect cyte packages.

[0048] Progcarousel: the working protocol of devices in the system.

[0049] Experimental Application (EA) : user defined protocols, for experimental procedure or measurements.

[0050] Operating system (OS): progcarousels that handle fundamental tasks such as scheduling the progcarousels, define basic operations.

[0051] FIG. 1 is an illustrative schematic of IBERS, as well as cyte and cyte files.

[0052] A Cyte (1), is the basic integrated processing unit combining biological material and the information associated with the said biological material in the system. A cyte 1 comprises the biological material 2 stored in a cyte vessel 45 and the metadata 3 associated with the cyte 1. The metadata 3 is the information regarding the biological material 2 and the cyte 1, typically including the information regarding the biological material within the cyte, the history of processes applied to cyte 1, the owner's information of cyte 1, etc. Each individual cyte 1 has a unique identifier 47. In one embodiment of cyte 1, metadata 3 is stored in a digital storage device 46 embedded in cyte vessel 45, optionally integrating unique identifier 47. In another embodiment of cyte 1, metadata 3 is stored outside cyte vessel 45 of cyte 1, and it is associated with said cyte 1 using identifier 47 of said cyte 1. In another embodiment of cyte 1, metadata is stored both inside said cyte 1 in the storage device 46, and outside said cyte 1 associated with said cyte 1 using the unique identifier 47. The identifier 47 embodiment integrated to cyte 1 is embedded to each individual cyte unit so that they can be distinguished from one another. The identifier 47 embodiment integrated to cyte 1 is optionally a physical engraving, a colored coded area, embedded circuits, or a combination of the above.

[0053] The metadata 3 comprises the following: source of the cyte, process history of the cyte, measurement data of the biological material inside corresponding to each process applied to the biological material 2 in the cyte 1, user info, etc. [0054] Operations applicable to a cyte 1 comprise operations of following categories: operations applicable to a cyte vessel 45 containing biological material 2, operations applicable to biological material 2, operations applicable to metadata 3, operations applicable to the linking between cyte 1 and metadata 3, and operations applicable to a cyte 1 as a whole. If not otherwise specified, operations applied to the content of cyte 1 is referred as "applied to cyte l"for clarity.

[0055] Operations applicable to a cyte vessel 45 containing biological material comprise the following: moving a cyte vessel 45, mounting a cyte 45 to a holder, registering the unique identifier 47 in a cyte 45 to a software, engraving marks on a cyte vessel 45, putting a cyte vessel 45 into cryogenic environment, putting a cyte vessel 45 into an environment of controlled atmosphere composition, centrifuging a cyte vessel 45, emptying a cyte vessel 45, opening a cyte vessel 45, closing a cyte vessel 45, sealing a vessel 45, adding substance into a cyte vessel 45, attaching electric connection to a cyte vessel 45, inserting devices into a cyte vessel 45, heating/cooling a cyte vessel 45, applying vacuum to a cyte vessel 45, packing cyte vessel 45 using other material, etc.

[0056] Operations applicable to biological material 2 comprise the following: adding substance to biological material 2, exposing biological material 2 to magnetic field, exposing biological material 2 to electric field, exposing biological material 2 to radiation including visible light, passing electric current through biological material 2, agitating biological material 2, drawing liquid from biological material 2, centrifuging biological material 2, applying vacuum or high atmospheric pressure to biological material 2, removing content from biological material 2, adding content to biological material 2, heating/cooling biological material 2, resuspending biological material 2 after centrifuging by adding liquid, culturing biological material 2 by adding medium and placing in corresponding culture environment etc.

[0057] Operations applicable to metadata 3 comprise the following: creating metadata 3 in a new cyte 1 unit, appending new entry to existing metadata 3, copying metadata 3 to another cyte 1 unit, deleting information from metadata 3 (possible to do but not allowed in most scenarios), merging different metadata 3 from different cyte 1 units into one metadata 3, displaying the information within metadata 3, etc.

[0058] Operations applicable to the linking between cyte 1 and metadata 3 comprise the following: linking the metadata 3 in an existing cyte 1 unit to another cyte 1 unit, linking multiple metadata 3 to one cyte 1 unit, etc.

[0059] Operations applicable to the entirety of cyte 1 unit comprise the following: creating a new cyte 1, copying/duplicating a cyte 1, combining multiple cyte 1 units into a new cyte 1, trash a cyte 1, move a cyte 1, modifying the content of a cyte 1, take measurements on a cyte 1, storing a cyte 1, freezing a cyte 1, thawing a cyte 1, sending/receiving a cyte 1, creating cyte files from multiple cyte 1 units, rearranging the location of cyte 1 units, etc.

[0060] A cyte file 4 is an ensemble of multiple cytes 1 grouped together based on the relation of their metadata 3. The cytes 1 within a cyte file 4 are optionally kept together physically, during operations applied to an entire cyte file 4.

[0061] A cyte file 4 includes a file metadata 5 comprising the metadata 3 of each cyte 1 within said cyte file 4, the relation between said metadata 3, as well as the information generated from said metadata 3; said file metadata 5 also records all the history of operation applied to cyte file 4. The file metadata 5 also includes the information the user input. Said file metadata 5 is optionally stored using the same method as cyte metadata 3. In one embodiment, said file metadata 5 is stored in an external location and linked to the unique identifier 47 of each cyte 1 units inside in said cyte file 4; in another embodiment, said file metadata 5 is stored together with each metadata 3 of the cyte 1 within said cyte file 4; in another embodiment, said file metadata 5 is stored in both locations described above.

[0062] Operations applicable to a cyte file 4 comprise the following: creating a cyte file 4 by grouping existing cyte 1, creating a cyte file 4 by duplicating one or multiple cyte 1 and grouping them, moving a cyte file 4 to another location, modifying the file metadata 5 of cyte files 4, etc.

[0063] The core features of a cyte 1 are as follow:

[0064] 1. A cyte 1 within the system is the basic unit (for all processes carried out in the system) combining biological material 2 and the information (metadata 3) associated with said cyte 1, which means any operation applied to the said biological material 2 within cyte 1 also generates a new entry appended to said metadata 3 containing existing information. Consequently, the metadata 3 of each cyte 1 contains the full history of said cyte 1 as well as of the biological material 2 within. [0065] 2. Multiple cytes 1 are able to be grouped into a cyte file 4, based on the relation among them; Meanwhile a cyte file metadata 5 is generated to store information associated with said cyte file 4. Cyte file metadata 5 is added to the metadata 3 of each cyte 1 within said group.

[0066] 3. Cyte 1 serves as a fundamental unit of information that can be referenced, cited, and transferred in a publication or other disclosure.

[0067] The architecture of the system (IBERS 6) to partially resembles the architecture of computers, comprising one or multiple of the following devices: Terminal 7, CPU 8, CAROUSEL 9, DISTRIBUTOR 10, PLU 11, GPU 12, PSU 13, WPS 14, Port 15, and LAN 16.

[0068] Terminal 7 is a device within the system, and users interacts with the system through it. Terminal 7 comprises the following components: a computer system, and specialized software interfaces. Users monitor the states of the system using terminal 7, and the terminal 7 reflects said states on real-time. Users create experimental application (EA 53) in terminal 7 and send them to CPU (process 21) using said software interface to execute them. Users also receive and output experimental results using said software interface. Users also send commands to each individual device within the system using terminal 7. User is also able to access (to read and to append) metadata 3 of cyte 1 stored in CAROUSEL (process 20).

[0069] CPU (Central Processing Unit) 8 is a device within the system comprising the following functions: converting EA 53 into detailed tasks for each device in the system, arranging the execution of each said tasks by coordinating the operations of said devices, carrying out automated applications, etc. Details of CPU 8 functionality is elaborated using the example in FIG.2.

[0070] CPU 8 enables the parallel processing of multiple EA simultaneously by scheduling and allocating PLU resources.

[0071] CAROUSEL (Random Access Memory) 9 is a device within the system that provides an adequate environment (such as temperature, humidity, atmosphere composition, illumination, agitation, etc.) for cytes 1, as CAROUSEL 9 is the primary incubator to keep (also to culture) cytes 1 that are not in the state of long-term storage. Cytes 1 are stored in CAROUSEL 9 for most of the time during experiments, and some measurements can be directly taken from cytes 1 in CAROUSEL 9. Cytes 1 are sent from CAROUSEL 9 to other devices in the system to perform tasks, and they are sent back to CAROUSEL 9 upon the completion of said tasks. CAROUSEL 9 provides both physical storage for cyte vessel 45 of cyte 1, as well as digital storage and access (read and write) to metadata 3 of said cyte 1. The location of cytes 1 in CAROUSEL 9 is also recorded in metadata 3 of said cytes 1, and the location information is monitored by CAROUSEL 9 and GPU 12.

[0072] DISTRIBUTOR (Internal Routing Nexus) 10 is a network connecting devices within the system, which is used to send cytes 1 from one device to another device (cyte transfer 17). DISTRIBUTOR 10 provides structure and protocol to send both cyte vessel 45 (physical entities) as well as metadata 3 (as well as access to metadata 3) of said cyte 1.

[0073] PLU (Procedure Logic Unit) 11 are devices within the system that carries out individual experimental tasks. PLUs are reconfigurable to perform different said tasks, and multiple units of PLU 11 can be implemented into the system. In order to perform said tasks, cytes 1 are transferred to designated PLU 11 from CAROUSEL 9 by DISTRIBUTOR 10, and subsequently transferred back to CAROUSEL 11 after the completion of said tasks at PLU 11.

[0074] Tasks performed by PLU 11 comprise the following: pipetting, adding reagents to cyte 1, removing content from cyte 1, duplicating cyte 1, merging multiple units of cyte 1, centrifuging cyte 1, applying vacuum to cyte 1, increasing air pressure inside cyte 1, perform flow cytometry on cyte 1, etc. PLU 11 also has temporary access to the metadata 3 of each cyte 1 processed within, and PLU 11 appends the information regarding experimental operations carried out upon said cyte 1 to said metadata 3.

[0075] Optimally, in the case where a waiting period is required between different steps performed within the same PLU 11, that cyte 1 is sent back to CAROUSEL 9 to wait, and it will be sent back to PLU 11 back again to continue the experiment. During the said waiting period, said PLU 11 optionally processes other cytes 1 based on the schedule generated by CPU 8.

[0076] GPU (Graphic Processing Unit) 12 is a device within the system that performs measurements (18) for one or multiple cytes 1 situated in CAROUSEL 9 and analyzes the data taken from measurement 18. GPU 12 is capable of performing measurement 18 upon multiple units of cyte 1 simultaneously. GPU 12 appends said data as well as results from said analysis to the metadata 3 of cyte 1 being measured. In addition, in the case where said cyte 1 being measured by GPU 12 belong to a cyte file 4, the information regarding measurement 18 is also appended to the file metadata 5 of said cyte file 4. The data analysis optionally includes and associates the locations of cyte 1 in CAROUSEL 9 with the variance of the measurement results. GPU 12 also sends the data or results to terminal 7 (data transfer 19) according to the EA 53 provided by the user. Some types of measurements 18 (basic information 52 such as cell counting and viability test) are carried out periodically with user-defined time interval; some types of measurements are performed while being requested by the EA 53 (or direct command of taking measurement) provided by user.

[0077] A partial list of GPU functionalities is provided: transmission spectroscopy, emission spectroscopy, fluorescence spectroscopy, Carouselen scattering spectroscopy, microscopy, imagery, high-speed photography, optical measurement without staining the biological material 3, etc.

[0078] PSU (Peripheral Storage Unit) 13 is a device within the system designated for cytes

1 storage. Compared to CAROUSEL 9 where cyte 1 are kept in an incubator-like environment, PSU 13 stores cytes 1 in ultra- low temperature (sometimes referred as "cryopreserve") to suppress the metabolism of the biological material 2 within said cyte 1. Therefore, PSU is designated to long-time storage (from months to years) of cyte 1. PSU 13 comprises the following modules: a cooling module (48), a storage repository (49), and a thawing module (50).

[0079] When one or multiple cytes 1 are to be cryopreserved in PSU 13, GPU 12 measures their basic information (52), appending the data to their metadata 3; subsequently said cytes 1 are transferred to PSU 13 by DISTRIBUTOR 10, accepted by the cooling module 48. Cooling module 48 cools said cyte 1 down to designated cryogenic temperature (no higher than -70°C), and transfers them to storage repository 49; the information of these processes is appended to the metadata 3 of said cyte 1 by the PSU 13. Methods of said cooling process comprises the following: single cell vitrification, controlled-rate cooling, single cyte vitrification, directional freezing (precisely control the formation of solidification within biological material 3), flow cytometry followed by vitrification (to selectively cryopreserve specific type of cells), etc.

[0080] When one or multiple cytes 1 are to be sent to CAROUSEL 9 from PSU 13, they are transferred to the thawing module 50 from storage repository 49. Thawing module 50 heats up the cytes 1 within according to pre-determined protocol, and the thawed cytes 1 are transferred to CAROUSEL 9 by DISTRIBUTOR 10. The information of said thawing process is also appended to the metadata 3 of said cyte 1. A measurement of basic information 52 is performed by GPU 12 immediately after the arrival of said cytes at CAROUSEL 9, and the results of said measurements are appended to the metadata 3 of said cyte 1. Methods of said thawing process comprises the following: controlled-rate thawing, directional thawing (precisely control the formation of melting within biological material 3), radiation heating, water bath, metal block heating, etc.

[0081] On the other hand, cyte 1 stored in the repository 49 (in their cryopreserved state) is transferred without being thawed to port 15 according to specific commands from terminal 7. Vice versa, cyte 1 in cryopreserved stated is transferred to repository 49 directly from port 15 without involving the cooling module 48 according to specific command from terminal 7. Optionally, repository 49 has a back-up storage unit to ensure the storage environment for cytes 1 within during a power outage or device malfunctioning.

[0082] WPS (Waste Processing System) 14 is a system within IBERS 6 that processes waste substances (chemical waste, biological waste, consumable waste) and trashed cyte 1. WPS 14 comprises the following components: a collecting system 102 (connected to PLU 11, CAROUSEL 9, PSU 13, and Port 15), a storage system for containers used for waste collection, a system to deactivate the microbe in wastes, etc.

[0083] Port 15 is a device within the system that imports cyte 1 to the system and exports cyte 1 from the system. Port 15 comprises the following components: a packaging module 61, a storage module 62 for package container (66), an unpacking module 63, an import/export module 64, an interface 65 with LAN 16, etc.

[0084] In the exporting operation, packaging module 61 accepts cyte 1 transferred from

CAROUSEL 7 (or PSU 13) . Subsequently, package container 66 is loaded from storage module 62 into packaging module 61, and said cyte 1 is packed by said package container 66. Next, the metadata 3 (also the information regarding the packing operation itself) of said cyte 1 are embedded into package container 66. Last, the packed cyte package 67 is transported to import/export module 64 (or interface 65 if LAN 16 is installed). Users pick up said package container 66 from the loading dock of import/export module 64 after it is ready.

[0085] A regular package container 66 used for cytes 1 from CAROUSEL 9 also possesses thermal-insulating properties such that the environment where the cytes are placed is stable during the transportation process. In addition to the properties of the regular package container 66, the specialized package container 66 used for cytes 1 from PSU 13 possesses the capability to maintain the low temperature environment for the cyte 1 within. Package container 66 optionally has a temperature logging module recording the temperature history of the cyte 1 within and sending warning if the temperature is going to exceed the preset threshold.

[0086] In the importing operation, users load the cyte package 67 into loading dock 60 of import/export module 64 (in the case of LAN 16 transportation, packages container 66 is directly sent into import/export module 64, bypassing loading dock 60). Subsequently, the package container 66 is transported to unpacking module 63 for unpacking, and the information regarding unpacking (also temperature history during transportation) is appended to the metadata 3 of said cyte 1. The cyte 1 within said package container 66 is transported to CAROUSEL 9 by DISTRIBUTOR 10, and said package container 66 is trashed (or stored to storage module 62 for specialized package container 66). GPU 12 measures their basic information (52) for said cyte 1, appending the data to their metadata 3. Alternatively, if the cyte 1 imported is in cryopreserved state (detected by port 15 using metadata 3 of said cyte 1), port 15 sends unpacked cyte 1 to the storage repository 49 of PSU 13.

[0087] A LAN (Local Area Nexus) 16 is an optional device connected to the port 15 of multiple instances IBERS 6, serving as a fast transportation network for cyte 1 among multiple instances of IBERS 6. LAN 16 comprises a cable system 68 transferring digital metadata 3, a conveyor system 69 transporting cyte package 67, one or multiple node 70 to regulate the traffic cyte package 67.

[0088] An illustrative example is described as follows to help elaborating how the system works, as shown in FIG.2.

[0089] First, a user wants to define an EA 53 using terminal 7, including the following steps: 1. Centrifuge two cytes of type A cell and discard the upper layer liquid (26); 2. Add reagent B to these cytes and culture for 48 hours (27); 3. Measure the average cell diameter (28); 4. Put the cytes back to storage (29). The operations within an EA 53 is defined as "application level (22)". Normally, a step at application level 22 is an experimental operation within a laboratory protocol.

[0090] After creating the said EA 53, the user gives terminal 7 a command to execute it so that said EA 53 is sent to CPU 8 via process 21. Subsequently, CPU 8 deconstructs (denoted by 30) each step of said EA 53 into a sequence of operations at operating system level (23) to be performed by different devices within the system to implement said operations. The deconstruction 30 of operations in application level 22 is based on the operating system pre-installed into CPU 8. For example, step 26 can be deconstructed into the following tasks: 1.1 CAROUSEL 9 locates the cytes 1 & 2 that contain type A cell based on the metadata 3 of each cyte 1 in CAROUSEL 9, and GPU 12 takes measurement for said cytes on cyte basic information 52 (31); 1.2 DISTRIBUTOR 10 sends cyte 1&2 to PLU-cfg (32); 1.3 PLU-cfg centrifuges cyte 1 & 2, and then discards the upper layer (33); 1.4 DISTRIBUTOR 10 sends cyte 1,2, and 3 back to CAROUSEL 9, and GPU 12 takes measurement for said cytes on cyte basic information 52 (34). Normally, a step at operating system level 23 is a high-level (does not contain detail such as gripper movement or pacarouseleters) task carried out by the system, and said steps are combined to complete each step at application level 22. Each measurement taken by GPU 12 is appended to the metadata 3 of corresponding cyte 1.

[0091] Next, CPU 8 further deconstructs (denoted by 35) each step at operating system level 23 into a sequence of tasks to be carried out by devices (device level 24), based on the design interfacing of each device within the system. For example, step 32 can be deconstructed into the following tasks: 1.2.1 DISTRIBUTOR 10 loads cyte 1 & 2 (36); 1.2.2 DISTRIBUTOR 10 sends cyte 1&2 to PLU-cfg (37); 1.2.3 DISTRIBUTOR drops off cyte 1 & 2, and PLU-cfg accepts them (38); 1.2.4 DISTRIBUTOR 10 handles other operations while PLU-cfg centrifuges cyte 1 & 2 (39). Normally, a step at device level 24 is an exact task for a device to do, and a combination of said steps complete each step high-level step carried at operating system level 23. CPU 8 also evaluates the duration and timing of each steps at device level 24 to schedule and coordinate the collaboration among devices.

[0092] CPU 8 sends steps at step at device level 24 to corresponding devices within the system, and said devices convert (denoted by 40) said steps into the most detailed step-by-step sequence of operation to be carried out by each individual device (operation level 25). For example, step 38 is deconstructed into the following tasks: 1.2.3.1 A gripper in PLU-cfg picks up cyte 1, and put it in rotor slot 1 (41); 1.2.3.2 DISTRIBUTOR 10 & rotor get ready for said gripper to pick up cyte 2 (42); said gripper picks up cyte 2 & put it in rotor slot 5 (43); 1.2.3.4 DISTRIBUTOR 10 disengages from PLU-cfg and PLU-cfg closes lid (44). Normally, a step at device level 24 is a list of fundamental operations carried out within a device to complete a step at device level. Said steps at operation 25 are controlled by individual devices.

[0093] FIG.3 shows the execution of said EA 53 (in FIG.2) at operating system level.

Numerals of devices what are introduced previous are omitted for clarity. Said EA 53 is sent to CPU 8 via process 21, and CPU 8 send the deconstructed internal commands 51 on device level 24 to each relevant device within the system so that each said internal command on device level is executed correctly according to the schedule generated by CPU 8.

[0095] Step 31 is executed within CAROUSEL 9. The subsequent step 32 where the resultant cyte 1& 2 are sent to PLU-cfg by DISTRIBUTOR 10 is denoted by arrow 32. Next, step 33 is executed in the PLU-cfg module, and the waste is collected by WPS 14 via waste collecting process 54. Next, in step 34 ,said cyte 1 & 2 are sent back to CAROUSEL 9 by DISTRIBUTOR 10. Subsequently, GPU 12 takes measurement for said cyte 1 & 2 on cyte basic information 52, as well as on cell diameter (55). Last, GPU 12 calculates average cell diameter based on the data of measurement 55, and transfer the result to terminal 7 for display via process 19 (56). It is noted that each operation is appended to the metadata 3 of corresponding cyte 1 & 2 by the device executing said operation. After the completion of measurement 55, said cyte 1 &2 are send to PSU 13 for long-term storage via cyte transfer 17 by DISTRIBUTOR 10.

[0096] The illustrative example in FIG.2 and FIG.3 describes a typical workflow of IBERS

6, and aiming to emphasize the following major features of the system:

[0097] 1. IBERS 6 is a closed system such that users only interact with it using port 15 for importing/exporting cyte 1, and terminal 7 for other purposes such as experiments, monitoring, data analysis, etc.

[0098] 2. In order to run an experiment, users create one EA 53 using terminal 7, and CPU

8 deconstructs said experimental application and distribute scheduled tasks to other devices within IBERS 6 to execute said tasks, as illustrated in FIG.2 and FIG. 3.

[0099] 3. Each device within IBERS 6 carries out the tasks given by CPU 8 according to the schedule associated with said tasks.

[00100] 4. The information, such as timestamp, pacarouseleters, data from measurements, results of analysis, of each operation carried out to a cyte 1 is appended to the metadata 3 of said cyte 1. [00101] An example of embodiments of cyte 1, and devices within IBERS 6 are described below, as shown in FIG.4.

[00102] Cyte container 45 comprises a main chamber 58 to store biological material 2, a lid 71 to prevent contamination, multiple flat surface 72 for optical measurement, channel/chamber 73 for cell counting, gripping site 74 for gripper to grip, unique identifier 47, and chip 46 to store metadata 3. In some embodiments the lid 71 is connected to the cyte container 45 so the two do not become separated.

[00103] The design above serves as a standard for container 45 of cyte 1, so that different specialized cyte container 45 are compatible with each other (also with the devices within in IBERS 6) following said standard.

[00104] Another embodiment of cyte container 45 for cyte 1 takes shape of a slide-like structure, as shown in FIG.5.

[00105] Instead of a conventional vial-like geometry, the slide-like structure provides the following advantages: higher surface to volume ratio which better for adherent cell, more compatible with planar manufacture technique (such as embossing, sheet forming and imprinting).

[00106] The components equivalent to those in FIG. 5 are labeled by identical numerals. Instead of a separated lid 71, this planar embodiment integrates the chamber 58 and lid 71 into a sandwich-like layer-by-layer structure, as shown in the lower sectional view in FIG.5. Two lid layers 71 sandwiches a structure layer, and the structural layer contains the geometries shown in the upper overhead view of FIG.5. The lid layers 71 are plane sheets of preferably plastic (e.g. polycarbonate, polyethylene, or polypropylene) or a glass material without features except for holes to add/remove biological material 2 from the main chamber 58. The embodiment of FIG. 4 can likewise be made of these same materials. Sidewall 74 are for gripping purposes. Chambers 73 are precise chambers for optical measurements, and some of said chambers has micro features to comply with specific type of experiments. Examples of micro features include micron size square wells to count individual cells, chemical treatment, antibody coatings, micro sensors/electrodes, etc. A pair of fluid inlet/outlet 79 is implemented to one or both lid layer 71. Chip 46 and 47 are on-cyte storage for metadata 3 and unique identifier respectively.

[00107] An illustrative of Terminal 7 display is shown in FIG.6. The terminal display 57 comprises the following windows: quick access bar 75, list of current tasks 76, IBERS Status display 77, and results display 78.

[00108] Display 77 dynamically reflects the status of each individual device within the system, by displaying the color-coded button. For example, in the case all the devices within the system are working properly, all the buttons corresponding to said devices light up in green. In the case of malfunctioning, the color of the button corresponding to the malfunctioning device changes to red and a warning window pops up. Also, the user who is responsible for the system gets text message notification or email notification, depending on the previous settings. On the terminal display 57, the user clicks the button in the said warning window to dismiss it, and then the user clicks the flashing-red button corresponding to said malfunctioning device to load a window displaying the details (results display 78) (the details are the raw measurement from sensors located at said devices and analyzed results of corresponding measurements).

[00109] Current task displays 76 shows the tasks currently running. Users click the corresponding button of each running tasks to look at the details of said tasks. The details comprising the following: the experimental application of the task, relevant measurements, current stage of the execution, etc. Users can stop any running EAs.

[00110] Quick access bar 75 is a user-defined toolbox providing convenient access to frequently used tools. One of said tools includes “New EA” to create new experimental applications. The inventory of PSU is also accessible through here. Moreover, user is able to access the metadata 3 of each cyte 1 in the system by clicking corresponding button, and said user is able to add more information to said metadata 3.

[00111] Terminal 7 outputs the metadata 3 of cytes 1 and cyte files 4 to external devices such as PCs, if being requested by user. The Terminal is optionally geologically far away from other devices of the system, enabling the user to work with the system remotely.

[00112] Terminal 7 combining port 15 also provides an option for user to manually create cyte 1. Users transfers biological material 3 into a new cyte 1 and load it to port 15. As the metadata 3 of said cyte 1 is factory default value, an initial metadata input window shows up in terminal 7 display 57 for user to input information regarding said cyte 1.

[00113] An illustrative example of the graphic experimental interface 80 (GEI, pop up after clicking “New EA” button in display 57) to build new EA 53 is shown in FIG.7.

[00114] GEI window 80 comprises the following sections: block library 81, application library 82, and current application zone 83. The block library 81 includes blocks 87 for user to drag-drop building EA 53, and said blocks are divided into three categories: cyte repository 84, operation 85, and measurement 86. Cyte repository 84 contains blocks representing each cyte 1 within the system so that users select which cyte 1 to work on. Operation 85 contains blocks 87 representing what-to-do with cyte 1, such as centrifuging or diluting. Measurement 86 contains blocks 87 representing the measurements as well as data analysis to be applied to cytes 1. Existing EAs 53 are displayed and accessible in application library 82.

[00115] Users drag and drop said blocks 87 to zone 83 to make an EA 53. An EA 53 starts with a “start” command 90 and an arrow depicting the direction of the workflow; an EA 53 ends with an “end” command 89. The workflow 88 is a resultant EA 53 resembling the EA in FIG. 2

[00116] Also, users are able to click into each block 87 to edit the pacarouseleters or use the default pacarouseleters. It should be noted that each step within workflow 88 are appended to the metadata 3 of corresponding cyte 1.

[00117] An embodiment of the configuration of IBERS 6 is illustrated in FIG.8.

[00118] This embodiment takes shape of a cylindrical configuration, where CAROUSEL 9, DISTRIBUTOR 10, and GPU 12 are located in a rotatable core able to rotate independently, and PLU 11, WPS 14, PSU 13, port 15 (not shown), are located on the circumference around the core.

[00119] Cyte 1 are stored in the radially spaced slots 100 in CAROUSEL 9, and

DISTRIBUTOR 10 has two cantilever- shaped transport beams 105 able to load cyte 1 from CAROUSEL. DISTRIBUTOR 10 rotates to adjust the tip-position of said beam to deliver said loaded cyte 1 to designated PLU 11. Vice versa, DISTRIBUTOR 10 sends cyte 1 back to CAROUSEL 9 using the same principle.

[00120] Multiple PLU 11 modules are installed, and they can be interchanged with other PLU 11 modules depending on the operations to be performed. Some PLU 11 module requires new cyte 1 unit feeding, which is supplied by a storage 99 (not shown) of unused cyte 1 units.

[00121] A Multiplier 59 is a specific type of PLU 11 configured and progcarouselmed to "copy" a cyte 1, which is a common experimental operation. After the original cyte 1 is sent to the multiplier, the multiplier activates a new inactivated cyte vessel 45 by registering its unique identifier 47 in the system and writing on its metadata 3. Designated quantity of biological material 3 is transferred from the original cyte 1 to this new cyte vessel 45, and this operation is also appended to the metadata 3 of both the original and the newly activated cyte 1 ; the metadata 3 of the original cyte 1 is also copied to the new one. Subsequently, both cytes 1 are sent back to CAROUSEL 9.

[00122] WPS 14 is an arc-shaped device spanning multiple PLU 11 so that the waste can be collected accordingly.

[00123] The cooling module 48 and thawing module 50 of PSU 13 are accessed separately by DISTRIBUTOR 10, and both modules are connected to storage repository 49 underneath.

[00124] A close-up view of CAROUSEL 9, DISTRIBUTOR 10, GPU 12, and a PLU 11 is shown in LIG. 9. Multiple slot 100 are radially spaced in an array of 5 in CAROUSEL 9 and multiple said array are spaced on the tangential direction of CAROUSEL 9. CAROUSEL 9 optionally has multiple levels and DISTRIBUTOR 10 optionally has multiple corresponding transporting mechanisms (beam rail 105). Multiple rails 105 are situated between DISTRIBUTOR core 103 (controllers) and DISTRIBUTOR base 106 (driving the rotation). Cytes 1 are transferred between the rail 105 of DISTRIBUTOR 10 and PLU 11 via the PLU 11 loading/unloading slot 101. GPU 12 optionally provides optics to take measurements on cyte 1 on different level of CAROUSEL 9.

[00125] An embodiment of GPU 12 is illustrated in PIG.10. GPU 12 comprises multiple optical measurement module 112, and each module has optics 111 on sliding rail 110 to perform measurements. The body of GPU 12 is rotatable so that each cyte 1 in slot 110 can be measured. The interface 116 for cyte 1 loading/unloading between DISTRIBUTOR 10 and other devices within the system is not shown. GPU 12 is rotatable on GPU core 113.

[00126] DISTRIBUTOR 10 and GPU 12 are located on the opposite side of CAROUSEL 10 so that then can operate independently without interferences. The site of measurement is noted by 114, where the optics 111 of GPU 12 is right underneath the cyte 1 to be measured. It should be noted that by implementing peripheral optics the optics 111 does not need to be placed underneath cyte 1 to perform measurements. [00127] The alignment of CAROUSEL 9, DISTRIBUTOR 10, and GPU 12 are illustrated in FIG. 11. Site 114 can be seen in the dashed circle where the optics 111 is right underneath the slot 100, so that multiple measurements on different cyte 1 can be perform simultaneously. It should be noted that optics 111 can move along both radial direction and tangential direction so that the site 114 does not have to be symmetric according to the central axis.

[00128] DISTRIBUTOR-CAROUSEL junction 115 are denoted by dashed ellipses where cyte 1 is picked up or dropped off by DISTRIBUTOR 10. It can be seen that rai 105 is aligned with the radial array of slot 100 so that multiple cytes 1 in said array can be accessed by said rail 105. DISTRIBUTOR 10 rotates with respected to CAROUSEL 9 to access different said array of cytes 1.

Claims

1. A system comprising: a container; a cavity defined within the container, and a first opening defined through the container to the cavity; an optically transparent window defined through the container, the window positioned such that light can pass through the window and into the cavity; a unique identifier attached to the container; and metadata associated with the unique identifier.

2. The system of claim 1 further comprising a semiconductor chip attached to the container and including the metadata.

3. The system of claim 2 wherein the semiconductor chip is embedded within the container or disposed on an exterior surface of the container.

4. The system of claim 1 further comprising an RFID tag embedded within the container and including the metadata.

5. The system of claim 1 wherein the metadata is stored in cloud storage.

6. The system of claim 1 wherein the unique identifier comprises a code printed on the container, or engraved on the container, or encoded in an RFID tag embedded within the container, or encoded by a semiconductor chip.

7. The integrated processing unit of claim 1-5 or 6 wherein the container comprises a shape of a microscope slide having two opposing faces, and wherein the window is disposed on one of the opposing faces.

8. The integrated processing unit of claim 7 wherein the container comprises two opposing layers separated by a structure layer, the structure layer including the cavity, the window defined in one of the two opposing layers.

9. The integrated processing unit of claims 7 or 8 further comprising a second opening defined through the container to the cavity.

10. The integrated processing unit of claim 7, 8, or 9 wherein the cavity comprises a main chamber in fluid communication with an auxiliary chamber, wherein the opening is in fluid communication with the main chamber and the window is positioned such that light can pass through the window and into the auxiliary chamber.

11. The integrated processing unit of claim 7-9 or 10 wherein the auxiliary chamber includes micro features.

12. The integrated processing unit of claim 1-5 or 6 wherein the container comprises a shape of a cuvette, the shape being symmetric around a longitudinal axis, wherein the opening is also symmetric around the longitudinal axis.

13. The integrated processing unit of claim 12 further comprising a removable lid fitted to seal the opening.

14. The integrated processing unit of claim 1-12 or 13 wherein the cavity includes a biological material and the metadata pertaining to that biological material.

15. An assembly comprising: a plurality of containers, each container including a cavity defined within the container and including a biological material, and a first opening defined through the container to the cavity, an optically transparent window defined through the container, the window positioned such that light can pass through the window and into the cavity, a unique identifier attached to the container; and metadata associated with each unique identifier, wherein at least some of the metadata across the plurality of containers share a relationship.

16. The assembly of claim 15 further comprising a semiconductor chip attached to each container and including the metadata associated with the unique identifier attached to that container.

17. The assembly of claim 16 wherein each semiconductor chip is embedded within the respective container or disposed on an exterior surface thereof.

18. The assembly of claim 15 wherein each container further comprises an RFID tag embedded within that container and including the metadata associated with the unique identifier attached to that container.

19. A system comprising: a core including a carousel having multiple slots, each slot configured to retain a container, an environmental control system configured to regulate environmental conditions within the slots; a procedure logic unit disposed proximate to the core and configured to receive a first container, to perform an experimental task on a biological material within the first container, and to write metadata including a result of the experimental task to a semiconductor chip attached to the first container; a distributor configured to remove the first container from a slot of the multiple slots and to transport the first container to the procedure logic unit; a computer system configured to allow a user to define an experimental application; and a CPU configured to receive the experimental application from the computer system and to execute the experimental application by causing the distributor to transfer the first container from the carousel to the procedure logic unit and by causing the procedure logic unit to execute the experimental task.

20. A method comprising: maintaining an environmental condition of a plurality of containers disposed in slots in a carousel; and executing an experimental application, including transferring a first container from the carousel to a procedure logic unit, causing the procedure logic unit to perform an experimental task on a biological material within the first container, including writing a result of the experimental task to a semiconductor chip attached to the first container, and transferring the first container from the procedure logic unit back to the carousel.