WO2010059569A2 - Analyzers and methods related thereto - Google Patents

Analyzers and methods related thereto Download PDF

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Publication number
WO2010059569A2
WO2010059569A2 PCT/US2009/064633 US2009064633W WO2010059569A2 WO 2010059569 A2 WO2010059569 A2 WO 2010059569A2 US 2009064633 W US2009064633 W US 2009064633W WO 2010059569 A2 WO2010059569 A2 WO 2010059569A2
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WO
WIPO (PCT)
Prior art keywords
analyzer
sample
assembly
probe
carousel
Prior art date
Application number
PCT/US2009/064633
Other languages
French (fr)
Other versions
WO2010059569A3 (en
Inventor
Michael F. Mcgrath
Amy E. Moseley
Vikram P. Mehrotra
Jeffrey A. Graham
Edward J. Cargill
Mark Ehrhardt
Thomas L. Bailey
Nagappan Mathialagan
Timothy Wilson
Eng Yeap
Arjun Vinoo Caprihan
Andrew Dowell
Rohan Smith
Kon Wong
Anthony Lele
Robert Metzke
Original Assignee
Monsanto Technology Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Monsanto Technology Llc filed Critical Monsanto Technology Llc
Publication of WO2010059569A2 publication Critical patent/WO2010059569A2/en
Publication of WO2010059569A3 publication Critical patent/WO2010059569A3/en

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/025Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes

Definitions

  • the present disclosure relates generally to analyzers. More specifically, the present disclosure relates to automated immunoassay analyzers (and related methods) suitable for performing colohmethc analyses, in-field, to determine, for example, pregnancy in bovine animals.
  • samples for desired traits are often done in controlled environments such as laboratories.
  • samples e.g., blood samples, etc.
  • desired subjects e.g., bovine animals, etc.
  • processed e.g., processed to form serum, etc.
  • assayed e.g., in microtiter plates, etc.
  • the desired subjects may be transported to the controlled environments, where samples are then taken, processed, assayed, and visually evaluated to determine if the desired traits are present.
  • an analyzer generally includes a housing, an incubation assembly located at least partially within the housing, a carousel assembly located at least partially within the incubation assembly and movable relative to the incubation assembly, and a probe assembly.
  • the carousel assembly is configured to support a sample vessel and a reaction vessel
  • the probe assembly is configured to wash the reaction vessel and transfer a sample contained within the sample vessel to the reaction vessel.
  • incubation assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits.
  • an incubation assembly generally includes a first insulating container defining a generally open interior region capable of receiving at least one or more processed samples to be analyzed for a desired trait, a second insulating container defining a generally open interior region, and a heating system disposed generally within the second insulating container.
  • the first insulating container is disposed at least partially within the generally open interior region of the second insulating container, and the heating system is operable to warm and/or help maintain a generally constant temperature of at least one or more processed samples.
  • a carousel assembly for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits.
  • a carousel assembly generally includes a first carousel configured to support at least one or more sample vessels generally around a perimeter of the first carousel, and a second carousel configured to support at least one or more reaction vessels generally around a perimeter of the second carousel. The first carousel is received at least partially within the second carousel.
  • At least one or more sample vessels and at least one or more reaction vessels are supported by the first and second carousels such that each sample vessel is correlated to a respective one of at least one or more reaction vessels, and such that each sample vessel is positioned radially adjacent its correlated reaction vessel.
  • Each of the one or more reaction vessels is configured to receive at least part of a sample from a correlated one of at least one or more sample vessels for analysis for a desired trait, and whereby each of at least one or more reaction vessels can be readily matched with the sample vessel from which the respective sample was received.
  • Various aspects of the present disclosure also relate generally to probe assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits.
  • the immunoassay analyzers support at least one or more sample vessels and at least one or more reaction vessels with each of at least one or more reaction vessels being correlated to each of at least one or more sample vessels.
  • the probe assemblies are operable to wash each of at least one or more reaction vessels and transfer at least part of a sample contained within each of at least one or more sample vessels to one or more correlated reaction vessels.
  • a probe assembly generally includes a support platform configured to be coupled to a work surface of an immunoassay analyzer, a first probe supported by the support platform and configured to generally wash each of at least one or more reaction vessels, a second probe supported by the support platform adjacent the first probe and configured to transfer at least part of a sample contained within each of at least one or more sample vessels to a correlated one of at least one or more reaction vessels, and a cleaning station configured to wash the first and/or second probes.
  • Various aspects of the present disclosure also relate generally to detection assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits.
  • the detection assemblies are operable to determine amounts of light absorbed and/or emitted by each of at least one or more processed samples for use in indicating presence and/or non-presence of the desired traits in each of at least one or more processed samples.
  • a detection assembly generally includes a first detector having a light source and a photodetector, and a second detector having a light source and a photodetector.
  • the first detector is configured to measure a first amount of light at a first wavelength passing through each of at least one or more processed samples to be analyzed for a desired trait by an immunoassay analyzer.
  • the second detector is configured to measure a second amount of light at a second wavelength passing through each of at least one or more processed samples to be analyzed for the desired trait by the immunoassay analyzer.
  • At least one or more processed samples are moved at a generally constant speed past the light source and the photodetector of the first detector and past the light source and the photodetector of the second detector.
  • the light source of the first detector emits light passing through at least one or more of the processed samples, and the photodetector of the first detector measures the amount of light at the first wavelength passing through each of the processed samples.
  • the light source of the second detector emits light passing through at least one or more of the processed samples, and the photodetector of the second detector measures the amount of light at the second wavelength passing through each of the processed samples.
  • kits for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits generally includes at least one or more sample vessels configured to receive a sample to be analyzed by an immunoassay analyzer for a desired trait, at least one or more reaction vessels capable of being correlated to at least one or more sample vessels and configured to receive at least part of the sample from at least one or more sample vessels for analysis by the immunoassay analyzer for the desired trait, at least one or more reagents configured to be added to at least one or more reaction vessels for reacting with said at least part of the sample received therein for use in preparing said sample for analysis by the immunoassay analyzer for the desired trait, a wash buffer for use in washing at least one or more reaction vessels before at least one or more sample vessels receive a reagent. At least one or more reaction vessels are generally coated with an antibody.
  • a method generally includes collecting a sample from an animal in a sample vessel, correlating the sample vessel containing the sample to the animal from which the sample was collected, positioning the sample vessel in an automated analyzer, positioning a reaction vessel in the automated analyzer in a position such that the reaction vessel can be correlated to the sample vessel, transferring at least part of the sample from the sample vessel to the reaction vessel, performing an enzyme-linked immuno-sorbent assay on the sample in the reaction vessel to produce a processed sample, and analyzing the processed sample after performing the enzyme-linked immuno-sorbent assay for presence and/or non- presence of at least one or more pregnancy-associated glycoproteins for indicating pregnancy and/or non-pregnancy in the animal.
  • FIG. 1 is an upper perspective view of an example embodiment of an analyzer including one or more aspects of the present disclosure
  • FIG. 2 is a lower perspective view of the analyzer of FIG. 1 ;
  • FIG. 3 is a block diagram of a control system of the analyzer of FIG.
  • FIG. 4 is the upper perspective view of FIG. 1 with a cover of a housing of the analyzer removed to show internal assemblies and components of the analyzer;
  • FIG. 5 is the upper perspective view of FIG. 4 with a cover of an incubation assembly of the analyzer removed to show a carousel assembly of the analyzer positioned generally within the incubation assembly;
  • FIG. 6 is a lower perspective view similar to FIG. 2 with the cover of the housing removed and with a base of the housing removed to show internal assemblies and components of the analyzer;
  • FIG. 7 is an upper perspective view of a body of the housing of the analyzer of FIG. 1 ;
  • FIG. 8 is a lower perspective view of the body of FIG. 7;
  • FIG. 9 is a fragmentary perspective view of the analyzer of FIG. 1 illustrating a reagent insert of the analyzer
  • FIG. 10 is a perspective view of containers configured to be supported in the reagent insert of the analyzer of FIG. 9;
  • FIG. 1 1 is an exploded perspective view of the carousel assembly of the analyzer of FIG. 1 ;
  • FIG. 12 is an upper perspective view of the carousel assembly of FIG. 1 1 assembled;
  • FIG. 13 is a lower perspective view of the carousel assembly of FIG. 12;
  • FIG. 14 is an example reaction vessel suitable for use with the analyzer of FIG. 1 ;
  • FIG. 15 is an upper perspective view of a probe assembly of the analyzer of FIG. 1 ;
  • FIG. 16 is a lower perspective view of the probe assembly of FIG. 15;
  • FIG. 17 is the upper perspective view of FIG. 12 rotated about one- hundred and eighty degrees
  • FIG. 18 is a partially exploded perspective view of the probe assembly of FIG. 15;
  • FIG. 19 is a perspective view of a cleaning station of the probe assembly of FIG. 15;
  • FIG. 20 is a longitudinal section view of the cleaning station of FIG. 19;
  • FIG. 21 A is a schematic of a pump system of the analyzer of FIG. 1 ;
  • FIG. 21 B is a schematic similar to FIG. 21 A with a transfer probe of the probe assembly shown rotated;
  • FIG. 22 is an exploded perspective view of the incubation assembly of the analyzer of FIG. 1 ;
  • FIG. 23 is a perspective view of a base support of the analyzer of FIG. 1 configured to support rotational movement of the carousel assembly during operation of the analyzer;
  • FIG. 24 is an upper perspective view of a detection assembly of the analyzer of FIG. 1 ;
  • FIG. 25 is a side perspective view of the detection assembly similar to that of FIG. 24 with part of the detection assembly broken away to show internal construction;
  • FIG. 26 is a schematic of a detector of the detection assembly of FIG. 24 with example movement of light through the detector shown in broken lines;
  • FIG. 27 is a bottom perspective view of the body of the housing of the analyzer of FIG. 1 illustrating the detection assembly coupled to an inner container of the incubation assembly;
  • FIG. 28 is a top plan view of the analyzer of FIG. 1 with a cover of the housing removed and illustrating example movement of a transfer probe of the probe assembly, with broken lines, during operation of the analyzer;
  • FIG. 29A is a schematic of an example assay timing diagram for operation of the analyzer of FIG. 1 ;
  • FIG. 29B is an enlarged fragmentary view of the schematic of FIG. 29A illustrating an example timing segment for transferring a sample from a sample vessel to a reaction vessel, using a transfer probe, cleaning the transfer probe, and incubating the reaction vessel;
  • FIG. 29B is an enlarged fragmentary view of the schematic of FIG. 29A illustrating an example timing segment for aspirating residual fluid from the reaction vessel, using a wash probe, washing the reaction vessel, adding reagent to the reaction vessel, and incubating the reaction vessel;
  • FIG. 30 is an example line graph illustrating example voltage drop across an example processed sample during analysis of the processed sample with the detection assembly of FIG. 24;
  • FIG. 31 is an upper perspective view of another example embodiment of an analyzer including one or more aspects of the present disclosure.
  • FIG. 32 is an upper perspective view of a carousel assembly of the analyzer of FIG. 31 ;
  • FIG. 33 is a schematic of an example kit configured for use with, for example, the example analyzer of FIG. 1 , the example analyzer of FIG. 31 , etc.;
  • FIG. 34 is a graph illustrating graphical results from testing described in Example 2 of the present disclosure.
  • Example embodiments will now be described more fully with reference to the accompanying drawings. [0053] Example embodiments are provided so that this disclosure will be thorough, and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific components, devices, assemblies, and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.
  • first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as “first,” “second,” and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the example embodiments.
  • Spatially relative terms such as “inner,” “outer,” “beneath”, “below”, “lower”, “above”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. Spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the example term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
  • Example automated analyzers can include, for example, automated immunoassay analyzers configured (e.g., sized, shaped, constructed, etc.) to test at least one or more samples for presence or non-presence of a desired trait. Some example analyzers may be operable to perform enzyme-linked immuno-sorbent assays (ELISAs) on at least one or more samples. Some example analyzers may be operable to test at least one or more biological samples taken from bovine animals for presence of at least one or more pregnancy-associated glycoproteins (PAGs).
  • ELISAs enzyme-linked immuno-sorbent assays
  • PAGs pregnancy-associated glycoproteins
  • PAGs are known and present at different times of bovine gestation
  • ELISAs performed by example immunoassay analyzers of the present disclosure can be used in the analyzers to detect, for example, at least one or more PAG isoforms (e.g., five PAG isoforms, etc.) as early as, for example, about day 25 in the bovine gestation cycle to help indicate pregnancy or non-pregnancy of the bovine.
  • PAG isoforms e.g., five PAG isoforms, etc.
  • Example compositions and methods for detecting early stage pregnancy in, for example, bovine animals is described in co- owned U.S. Provisional Patent Application No. 61/013,603, filed December 13, 2007, the entire disclosure of which is incorporated herein by reference.
  • FIGS. 1-30 illustrate an example embodiment of an analyzer 100 including one or more aspects of the present disclosure.
  • the illustrated analyzer 100 is configured, for example, to test at least one or more samples for a desired trait.
  • Tests may include immunoassay tests (e.g., an enzyme-linked immuno-sorbent assays (ELISA), etc.), and samples may include solid samples (e.g., dry samples to which liquid is later added for analysis, etc.), liquid samples, etc. obtained from any suitable source.
  • immunoassay tests e.g., an enzyme-linked immuno-sorbent assays (ELISA), etc.
  • samples may include solid samples (e.g., dry samples to which liquid is later added for analysis, etc.), liquid samples, etc. obtained from any suitable source.
  • liquid samples may include liquid analyte samples such as biological samples (e.g., whole- blood samples, urine samples, saliva samples, milk samples, plasma samples, serum samples, etc.) obtained from one or more animals (e.g., bovine animals, animals from the order Artiodactyla (e.g., ungulates including, but not limited to, camels, horses, deer, cows, goats, pigs, sheep, whales, etc.), etc.).
  • Desired traits may include presence and/or non-presence of at least one or more pregnancy indicators, for example, at least one or more pregnancy-associated glycoproteins (PAGs).
  • PAGs pregnancy-associated glycoproteins
  • Desired traits may also include other pregnancy related factors; presence and/or non-presence of progesterone; presence and/or non-presence of positive energy balance indicators (e.g., blood ketones in cows, etc.), health status indicators (e.g., disease indicators such as for Johnes Disease, etc.); etc.
  • positive energy balance indicators e.g., blood ketones in cows, etc.
  • health status indicators e.g., disease indicators such as for Johnes Disease, etc.
  • the illustrated analyzer 100 is an automated analyzer 100 capable of in-field analysis.
  • biological samples received from one or more cows on a farm can be processed by the analyzer 100 in-field at the farm for presence and/or non-presence of at least one or more PAGs.
  • the samples can be taken directly from the cows (and correlated to the cows from which they are taken), placed into the analyzer 100, and processed in-field at the farm (e.g., without having to send the samples to a lab, etc.).
  • the illustrated analyzer 100 may initially perform an ELISA on each of the samples (e.g., after the samples are transferred from sample vessels to reaction vessels, etc.), and then optically analyze each of the processed samples (e.g., within the reaction vessels, etc.) for the presence and/or non-presence of at least one or more PAGs.
  • a blue colored processed sample (e.g., within a reaction vessel, etc.), following the ELISA, may indicate the presence of at least one or more PAGs in the processed sample (and thus that the cow from which the sample was taken is pregnant); and a clear processed sample (or uncolored processed sample, or faintly colored processed sample, etc.), following the ELISA, may indicate the non-presence of at least one or more PAGs in the processed sample (and thus that the cow from which the sample was taken is not pregnant, or open).
  • Other colors may be used as indicators of presence and/or non-presence of a trait in a processed sample within the scope of the present disclosure.
  • processed samples can include samples, fluids, etc. on which an ELISA or other reaction has been performed, for example, in preparation for further analysis.
  • fluid within a reaction vessel following steps of an ELISA or other reaction, etc. can include a processed sample.
  • the analyzer 100 includes a housing 102 having a body 104, a cover 106, and a base 108 (FIG. 2).
  • the cover 106 is coupled to the body 104 by hinges 109 (FIG. 1 ), which allow the cover 106 to pivot relative to the body 104 to selectively open and/or close the cover 106.
  • the cover 106 When the cover 106 is in an open position, for example, samples may be placed into the analyzer 100 for processing; and when the cover 106 is in a closed position, for example, the cover 106 helps protect at least one or more assemblies, other components, etc.
  • the base 108 is coupled to an underside of the body 104 (FIG. 2), for example by mechanical fasteners, etc. (not shown), to help further protect at least one or more assemblies, other components, etc. of the analyzer 100 (and/or samples placed in the analyzer 100 for processing) against ingress of contaminants into the analyzer 100, inadvertent contact during sample processing, etc.
  • the base 108 is coupled to an underside of the body 104 (FIG. 2), for example by mechanical fasteners, etc. (not shown), to help further protect at least one or more assemblies, other components, etc. of the analyzer 100 (and/or samples placed in the analyzer 100 for processing) against ingress of contaminants into the analyzer 100, inadvertent contact during sample processing, etc.
  • Different assemblies of the analyzer 100 located within the housing 102 will be described in further detail hereinafter.
  • the analyzer 100 also includes a control system 1 10 (e.g., an internal computer system, etc.) for use in controlling and/or operating the analyzer 100.
  • the control system 1 10 can control operation of at least one or more of the assemblies, components, etc. of the analyzer 100 for processing one or more samples placed into the analyzer 100.
  • the control system 1 10 may also enable data storage and data manipulation in connection with sample analysis, as will be described in more detail hereinafter.
  • the illustrated control system 1 10 generally includes first and second microcontrollers 1 12 and 1 14 that include, for example, central processing units (CPU), memory, interfaces for communicating with at least one or more of the assemblies, components, etc. of the analyzer 100, sensors, motors, external components (e.g., a PC, a printer, etc.) for monitoring, controlling, reporting, recording, etc. operation of at least one or more of the assemblies, components, etc., and a user interface (e.g., a graphics user interface (GUI), etc.) configured to receive data input and/or display data output in connection with operation of the analyzer 100.
  • the illustrated memory includes software and data for performing various operations and controls of the analyzer 100.
  • the illustrated memory includes software modules such as an operating system; one or more assembly control modules including instructions for operating and controlling at least one or more of the assemblies, components, etc. of the analyzer 100; assay protocols; analyzer self-cleaning and washing protocols; data analysis, processing, and storage modules; expert system support modules; scheduling modules containing instructions and/or data related to scheduling assays and procedures; workflow control; and service support.
  • Software modules such as an operating system; one or more assembly control modules including instructions for operating and controlling at least one or more of the assemblies, components, etc. of the analyzer 100; assay protocols; analyzer self-cleaning and washing protocols; data analysis, processing, and storage modules; expert system support modules; scheduling modules containing instructions and/or data related to scheduling assays and procedures; workflow control; and service support.
  • Memory may include more or less modules than disclosed herein, and/or may include at least one or more different modules than disclosed herein within the scope of the present disclosure.
  • control systems may include less than or more than two microcontrollers configured the same or differently than disclosed herein.
  • the illustrated control system 1 10 may allow for the analyzer 100 to interface with various different software programs (e.g., spreadsheet programs such as Excel, etc.; dairy management software such as DairyComp 305, etc.; etc.).
  • the software programs may be running on the control system 1 10.
  • the software programs may, for example, be running on at least one or more external control systems such as external personal computers, etc. coupled to the analyzer 100.
  • the illustrated control system 1 10 may allow for output of test results in at least one or more different data formats, such as, for example, comma- separated values (CSV), etc.
  • the user interface of the control system 1 10 may allow for easy indexing through, for example, a liquid crystal display (LCD) and membrane keypad 1 16 (FIG. 1 ) (broadly, a user interface).
  • LCD liquid crystal display
  • FIG. 1 membrane keypad 1 16
  • the LCD and membrane keypad 1 16 is positioned generally within the body 104 of the analyzer 100 toward a forward part of the housing 102.
  • a serial bus (e.g., RS232, etc.) 1 17 is provided along a rearward side of the body 104 for attaching at least one or more types of serial peripheral devices (e.g., a printer, etc.).
  • a universal serial bus (USB, not shown) may be provided for coupling at least one or more types of USB peripheral devices (e.g., a PC, etc.) to the analyzer 100 as desired.
  • analyzers may include at least one or more external control systems such as external personal computers, etc.
  • the external control systems may allow for connection of additional peripherals to the analyzers including, for example, one or more monitors, keyboards, trackballs, mice, printers, other peripheral input and/or output devices, etc.
  • the analyzer 100 generally includes, disposed generally within the housing 102, a carousel assembly 1 18 (FIG. 5), a pump system 120, a probe assembly 122, an incubation assembly 124, and a detection assembly 126 (not visible in FIGS 4-6 but described hereinafter in more detail with reference to FIGS. 24-27).
  • the pump system 120, the probe assembly 122, and the incubation assembly 124 are generally supported by a work surface 128 (FIG. 7, broadly, a platform) located within the housing 102.
  • the probe assembly 122 is positioned adjacent the incubation assembly 124, and the carousel assembly 1 18 and detection assembly 126 are located generally within the incubation assembly 124.
  • a waste container 125 is coupled to the housing 102 outside the analyzer 100 to receive, for example, aspirated waste from the probe assembly 122, etc.
  • a wash buffer container 127 holding reaction vessel wash fluid is also coupled to the housing 102 outside the analyzer 100.
  • the carousel assembly 1 18 is configured to support at least one or more sample vessels (e.g., sample vessels containing samples, etc.) and at least one or more reaction vessels (e.g., reaction vessels for use in performing assays on the samples, etc.) within the incubation assembly 124.
  • the probe assembly 122 (in operation with the pump system 120 and the carousel assembly 1 18) is configured to transfer at least part of a sample contained within the sample vessels to a correlated one of the reaction vessels for processing, analysis, testing, assay, etc.
  • the probe assembly 122 is also configured to wash at least one or more reaction vessels as desired.
  • the incubation assembly 124 is configured to maintain a temperature of the reaction vessels in the carousel assembly 1 18 (e.g., after a sample is transferred thereto, etc.) and/or to increase and/or to decrease a temperature of (e.g., heat, warm, cool, etc.) the reaction vessels as desired.
  • the detection assembly 126 is configured to detect presence of color (or lack thereof) in processed samples within the reaction vessels as an indicator of presence and/or non-presence of a desired trait.
  • the illustrated work surface 128 of the housing 102 is generally formed as part of the housing's body 104 and includes, for example, an opening 129 for receiving and/or supporting the probe assembly 122, and pump openings 130 for supporting pumps 131 , 132, 133, and 134 (FIGS. 4 and 5) of the pump system 120.
  • an opening 129 for receiving and/or supporting the probe assembly 122
  • pump openings 130 for supporting pumps 131 , 132, 133, and 134 (FIGS. 4 and 5) of the pump system 120.
  • conduits coupling the pumps, etc. to the probe assembly, etc. are not shown in the drawings.
  • the illustrated work surface 128 receives and/or supports, within a receptacle 135 of the housing 102 (FIGS. 7 and 8), a reagent insert 136.
  • the reagent insert 136 is configured to hold containers used during operation of the analyzer 100, for example, operation of the pump system 120, the probe assembly 122, etc.
  • the receptacle 135 is defined in the work surface 128 to selectively receive the reagent insert 136 into the housing 102 and/or to selectively allow the reagent insert 136 to be removed from the housing 102.
  • the reagent insert 136 is configured to hold four reagent containers 137, 138, 139, 140 and containers 141 and 142 containing system cleaning/rinsing fluids (e.g., water, cleaning solutions, etc.).
  • analyzers may include work surfaces and/or reagent inserts configured to hold different numbers of and/or types of containers (e.g., more than or less than four reagent containers, etc.).
  • analyzers may include containers of which all or some are located inside or outside the analyzers.
  • the example carousel assembly 1 18 generally includes an inner carousel 144 configured to hold sample vessels 145 (FIGS.
  • the inner carousel 144 and the outer carousel 146 each include vessel support openings 148 extending generally around their perimeters for receiving and supporting the sample vessels 145 and reaction vessels 147.
  • the vessel support openings 148 of the inner carousel 144 each include an opening extending through an upper flange 149 of the inner carousel 144 and an aligned recessed opening formed in a lower flange 150 of the inner carousel 144.
  • a sample vessel 145 can be positioned through the opening in the upper flange 149 and into the recessed opening in the lower flange 150 such that the sample vessel 145 is securely supported within the vessel support opening 148 of the inner carousel 144.
  • the vessel support openings 148 of the outer carousel 146 include an opening extending through an upper flange 151 of the outer carousel 146 and an aligned recessed opening formed in a lower flange 152 of the outer carousel 146.
  • a reaction vessel 147 can be positioned through the opening in the upper flange 151 and into the recessed opening in the lower flange 152 such that the reaction vessel 147 is securely supported within the vessel support opening 148 of the outer carousel 146.
  • the inner carousel 144 is received generally within the outer carousel 146.
  • the outer carousel 146 includes an inner channel 154 (FIG. 1 1 ) within which the inner carousel 144 is received.
  • a retaining clip 155 located along an inner portion of the outer carousel's upper flange 151 is received within a notch 156 located along an outer portion of the inner carousel's upper flange 149 to couple (e.g., releasably couple, snap connect, etc.) the inner carousel 144 to the outer carousel 146 within the inner channel 154.
  • a handle 158 is provided generally across an upper portion of the inner carousel 144 such that a user can grasp the handle 158, for example, to move the inner and outer carousels 144 and 146 (e.g., when the inner carousel 144 and outer carousel 146 are coupled together, etc.), to position the carousels 144 and 146 within the incubation assembly 124, to remove the carousels 144 and 146 from the incubation assembly 124, to wash the carousels 144 and 146, etc. as desired.
  • each sample vessel 145 received into a vessel support opening 148 of the inner carousel 144 is generally correlated with a respective reaction vessel 147 received into a vessel support opening 148 of the outer carousel 146.
  • each vessel support opening 148 of the inner carousel 144 is positioned radially adjacent its correlated vessel support opening 148 of the outer carousel 146.
  • control fluids are provided in the sample vessels 145 positioned in the sample vessel support openings 148 of the inner carousel 144 identified by the letter indicia "A" and "B".
  • the vessel support openings 148 of the inner carousel 144 may be sized differently than the vessel support openings 148 of the outer carousel 146 to help facilitate proper placement of sample vessels 145 in the inner carousel 144 and reaction vessels 147 in the outer carousel 146.
  • the vessel support openings 148 of the inner carousel 144 may be larger than the vessel support openings 148 of the outer carousel 146.
  • the sample vessels 145 may be sized larger than the reaction vessels 147 (corresponding to the sizes of the vessel support openings 148 in the inner and outer carousels 144 and 146) such that the sample vessels 145 cannot be placed in the vessel support openings 148 of the outer carousel 146.
  • vessel support openings of inner carousels may be smaller than vessel support openings of outer carousels, and sample vessels may be sized smaller than reaction vessels (corresponding to the sizes of the vessel support openings in the inner and outer carousels) such that the reaction vessels cannot be placed in the vessel support openings of the inner carousels.
  • tube shape may be used to help position sample vessels and/or reaction vessels in proper openings.
  • the correlated relationship between the vessel support openings 148 of the inner and outer carousels 144 and 146 can provide for a known relationship between a sample (e.g., a sample received into a sample vessel 145 positioned in the inner carousel 144, etc.) and an assay performed on the sample (e.g., an assay performed in a reaction vessel 147 on at least part of a sample taken from a correlated sample vessel 145, etc.) such that the assay results can be subsequently correlated to the original sample (e.g., via the control system 1 10, etc.).
  • a sample e.g., a sample received into a sample vessel 145 positioned in the inner carousel 144, etc.
  • an assay performed on the sample e.g., an assay performed in a reaction vessel 147 on at least part of a sample taken from a correlated sample vessel 145, etc.
  • the inner carousel 144 includes vessel support openings 148 configured to hold thirty sample vessels 145 and two sample vessels 145 with control fluids
  • the outer carousel 146 includes vessel support openings 148 configured to hold thirty-two correlated reaction vessels 147.
  • carousel assemblies may be configured to hold more or fewer sample vessels and/or reaction vessels than disclosed herein.
  • a drive mechanism (not shown) is provided for conjointly rotating the inner and outer carousels 144 and 146 generally within (and relative to) the incubation assembly 124 during operation of the analyzer 100.
  • a motor can interact with teeth 153 of the outer carousel 146 to rotate the outer carousel 146 (and thus the inner carousel 144 coupled thereto) within the incubation assembly 124.
  • FIG. 14 illustrates an example reaction vessel 147 suitable for use with the illustrated analyzer 100.
  • the reaction vessel 147 is generally elongate and tubular in shape, and includes a body 159, an upper open end portion 160, and a lower closed end portion 161.
  • Internal ribs 162 (or fins) are provided within the reaction vessel 147 generally toward the lower closed end portion 161 .
  • Inner surfaces of the illustrated reaction vessel 147 (including the ribs 162) are coated with, for example, an antibody (e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.).
  • an antibody e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.
  • the antibody may facilitate or initiate a reaction (e.g., an ELISA reaction, etc.) and capture one or more PAGs which then start to promote the reaction.
  • the ribs 162 may help improve completeness of the reaction within the reaction vessel 147 as the ribs 162 increase surface area in the reaction vessel 147 over which the reactions may take place.
  • reaction vessels may include shapes other than disclosed herein, for example rectangular shapes (e.g., cuvettes, etc.), etc.
  • reaction vessels may be coated with at least one or more other antibodies, other materials, or may be free of any coatings.
  • reaction vessels may include other structures to increase surface area within the reaction vessels (e.g., for reactions to occur within the vessels, etc.), such as, for example, grooves, beads, etc.
  • reaction vessels without fins may be used (with or without antibody coatings).
  • Sample vessels suitable for use with the illustrated analyzer 100 may include any suitable sample vessels capable of receiving samples.
  • the sample vessels may include VACUTAINER tubes (e.g., ten milliliter VACUTAINER tubes, etc.), or any other suitable vessels within the scope of the present disclosure.
  • the probe assembly 122 generally includes an automated fluid transfer system 164 and an automated reaction vessel wash system 166.
  • the fluid transfer system 164 operates to transfer a sample (including one or more control fluids) from sample vessels to correlated reaction vessels.
  • the fluid transfer system 164 also operates to transfer at least one or more reagents (e.g., from reagent containers 137, 138, 139, and. /or 140, etc.) to the reaction vessels for generally initiating a reaction on the samples in the reaction vessels as desired.
  • the reaction vessel wash system 166 operates to wash, clean, etc.
  • the fluid transfer system 164 and/or the reaction vessel wash system 166 may be at least partially manual systems.
  • first and second guide posts 165 are generally supported along respective first and second guide posts 165 and
  • the upper support platform 168 and 169 couple the fluid transfer system 164 and reaction vessel wash system 166 to the body 104 and work surface 128 of the analyzer's housing 102.
  • the upper support platform 168 can be coupled to a rearward wall 170 of the body 104
  • the lower support platform 169 can be coupled to or integrated into the work surface 128 generally within the work surface's second opening 129.
  • Suitable means may be used to couple the upper support platform 168 to the body 104 and/or the lower support platform 169 to the work surface 128, for example, mechanical fasteners, welds, integral forming means, etc. within the scope of the present disclosure.
  • the fluid transfer system 164 generally includes a transfer probe 172 (e.g., an automated robot transfer probe, etc.) for transferring a sample contained within a sample vessel to a correlated reaction vessel, and for then transferring a reagent from a reagent container (e.g., 137, 138, 138, 140, etc.) to the correlated reaction vessel.
  • the fluid transfer system 164 also includes a frame structure 173 supporting the transfer probe 172, and a drive mechanism 174 coupled to the frame structure 173 for moving the frame structure 173 and transfer probe 172 in a generally vertical direction (e.g., a generally z-direction, etc.) and in a generally rotational direction. This generally vertical and generally rotational operation of the transfer probe 172 can help minimize an operational footprint of the probe assembly 122.
  • the transfer probe 172 includes a support body 176 and a continuous flexible inner tube 177 extending through the support body 176.
  • the support body 176 and tube 177 couple to a head 178, which in turn couples to the frame structure 173 (e.g., releasably couples thereto via a thumbscrew 181 , etc.).
  • the support body 176 may be formed to help keep the tube 177 generally straight through the support body 176 (e.g., help inhibit inadvertent bending of the tube 177, help protect the tube 177, etc.) during repeated use/operation of the transfer probe 172 (e.g., fluid transfer via the tube 177, etc.).
  • the support body 176 and the tube 177 may be formed from materials that promote easy cleaning, durability, reusability, etc.
  • the support body 176 may be formed from stainless steel, etc.
  • the tube 177 may be formed from TEFLON, etc.
  • the fluid transfer system 164 can also operate to wash the transfer probe 172 as necessary (e.g., using the system cleaning/rinsing fluids, etc.).
  • the frame structure 173 of the fluid transfer system 164 is coupled to the first guide post 165 (e.g., by spherical bearings, etc.) for supporting sliding movement of the frame structure 173 (and transfer probe 172) along the first guide post 165 during operation.
  • This allows the drive mechanism 174 to move the transfer probe 172 (via the frame structure 173) generally vertically into and/or out of sample vessels received within the carousel assembly 1 18, into and/or out of reaction vessels received within the carousel assembly 1 18, and into and/or out of reagent containers (e.g., 137, 138, 138, 140, etc.) supported by the work surface 128.
  • reagent containers e.g., 137, 138, 138, 140, etc.
  • the frame structure 173 is also positioned along the first guide post 165 for supporting rotational movement of the frame structure 173 (and transfer probe 172). This allows the drive mechanism 174 to rotate the transfer probe 172 between sample vessels, reaction vessels, reagent containers (e.g., 137, 138, 138, 140, etc.), and a cleaning station 182 during operation.
  • sample vessels reaction vessels
  • reagent containers e.g., 137, 138, 138, 140, etc.
  • the illustrated drive mechanism 174 of the fluid transfer system 164 includes a rack-and-pinion gear drive mechanism to move the transfer probe 172 generally vertically, and a rotational gear drive mechanism to move the transfer probe 172 generally rotationally.
  • the rack-and- pinion gear drive mechanism includes a rack 185 positioned along the frame structure 173 and extending through the lower support platform 169, and a pinion 186 positioned generally under the lower support platform 169 in engagement with the rack 185.
  • a first motor 187 positioned generally under the lower support platform 169 drives the generally linear, vertical movement of the transfer probe 172 (via the rack 185 and pinion 186).
  • a second motor 188 is positioned generally under the lower support platform 169 to rotate the transfer probe 172 via a gear 189.
  • the reaction vessel wash system 166 generally includes a wash probe 190 (e.g., an automated robot wash probe, etc.) for washing, cleaning, etc. reaction vessels, a frame structure 191 supporting the wash probe 190, and a drive mechanism 192 coupled to the frame structure 191 for moving the frame structure 191 and wash probe 190 in a generally vertical direction (e.g., a generally z-direction, etc.).
  • a wash probe 190 e.g., an automated robot wash probe, etc.
  • a frame structure 191 supporting the wash probe 190 e.g., a generally z-direction, etc.
  • This generally vertical operation of the wash probe 190 can help minimize an operational footprint of the probe assembly 122.
  • the illustrated wash probe 190 includes a generally dual member structure (e.g., a dual probe-member structure, etc.). It includes a dispensing member 194 (e.g., a dispensing probe member, etc.) and an aspirating member 196 (e.g., an aspirating probe member, etc.) coupled to a head 197, which is releasably coupled to the frame structure 191 (e.g., via a thumbscrew 181 , etc.).
  • the dispensing member 194 includes a support body 198 (or sleeve) and a continuous flexible inner tube 199 extending through the support body 198.
  • the aspirating member 196 includes a support body 202 (or sleeve) and a continuous flexible inner tube 203 extending through the support body 202.
  • the support bodies 198 and 202 of the dispensing member 194 and/or of the aspirating member 196 may be formed to help keep the respective tubes 199 and/or 203 generally straight through the support bodies 198 and 202 (e.g., help inhibit inadvertent bending of the tubes 199 and 203, help protect the tubes 199 and 203, etc.) during repeated use/operation of the wash probe 190 (e.g., fluid transfer via the tubes 199 and/or 203, etc.).
  • the support bodies 198 and 202 and the tubes 199 and 203 of each member 254, 256 may be formed from materials that promote easy cleaning, durability, reusability, etc.
  • the support body 198 of the dispensing member 194 and/or the support body 202 of the aspirating member 196 may be formed from stainless steel, etc.
  • the tube 199 of the dispensing member 194 and/or the tube 203 of the aspirating member 196 may be formed from TEFLON, etc.
  • separation of the dispensing member 194 and the aspirating member 196 in the wash probe 190 may help reduce and/or minimize contamination in the reaction vessels during washing operation of the reaction vessels.
  • uncontaminated wash buffer can be introduced (e.g. pumped from the wash buffer container 127 (FIG. 4), etc.) into the reaction vessels for washing by the dispensing member 194, and then aspirated from the reaction vessels by the separate aspirating member 196 (e.g., to the waste container 125 (FIG. 4), etc.). Any reaction residue in the reaction vessel is also aspirated by (and through) the aspirating member 196 separate from the dispensing member 194.
  • analyzers may include wash probes in which dispensing functions and aspirating functions are performed by single bodies and/or tubes of the wash probes.
  • the frame structure 191 of the reaction vessel wash system 166 is positioned generally along the second guide post 167 for supporting sliding movement of the frame structure 191 (and wash probe 190) along the second guide post 167 during operation. This allows the drive mechanism 192 to move the wash probe 190 (via the frame structure 191 ) generally vertically into and/or out of reaction vessels received within the carousel assembly 1 18 for washing, cleaning, etc. the reaction vessels.
  • the illustrated drive mechanism 192 of the reaction vessel wash system 166 includes a rack-and-pinion gear drive mechanism to move the wash probe 190 generally vertically.
  • a rack 204 is positioned along a lower part of the frame structure 191 and extends through the lower support platform 169, and a pinion 205 is positioned generally under the lower support platform 169 in engagement with the rack 204.
  • a motor 206 positioned generally under the lower support platform 169 operates to rotate the pinion 205 as desired to drive the generally linear, vertical movement of the wash probe 190 (via the rack 204 and pinion 205).
  • the frame structure 173 of the illustrated fluid transfer system 164 includes an upper arm 207 to which the head 178 of the transfer probe 172 can be coupled.
  • the frame structure 191 of the illustrated reaction vessel wash system 166 also includes an upper arm 208 to which the head 197 of the wash probe 190 can be coupled.
  • the heads 178 and 197 are removable to help facilitate generally easy replacement of the transfer probe 172 and wash probe 190 if either becomes damaged.
  • Thumbscrews 181 are provided for removably coupling the heads 178 and 197 to the respective upper arms 207 and 208.
  • the frame structure 173 of the fluid transfer system 164 also includes fluid sensors 210 mounted on its upper arm 207 (adjacent the tube 177) for use in controlling dispensing operations of the transfer probe 172.
  • the fluid sensors 210 may also provide indirect means to detect blockage within the transfer probe 172 and/or transfer system 164 (e.g., within the tube 177, other conduits, etc. of the fluid transfer system 164, etc.).
  • the cleaning station 182 of the probe assembly 122 is configured to wash, clean, etc. the transfer probe 172 of the fluid transfer system 164 between fluid transfer operations.
  • the transfer probe 172 may be cleaned after each sample transfer from a sample vessel to a reaction vessel, after each reagent transfer to a reaction vessel, etc.
  • a tip portion of the transfer probe 172 is positioned within a first, wider well 212 of the cleaning station 182 and wash fluid (e.g., wash buffer from the wash buffer container 127, cleansing/rinsing fluids from the containers 141 and 142, etc.) is dispensed through the transfer probe 172 for internal cleaning.
  • wash fluid e.g., wash buffer from the wash buffer container 127, cleansing/rinsing fluids from the containers 141 and 142, etc.
  • the wash fluid is discharged out of the transfer probe 172 into the first well 212 and transferred (e.g., aspirated via the pump system 120, etc.) through an outlet 213 to the waste container 125 (e.g., via tubing (not shown) coupled to the outlet and waste container 125, etc.).
  • the transfer probe 172 is then moved into a second, narrower well 214 while still dispensing wash fluid.
  • the wash fluid shears up the sides of the second well 214, effectively increasing the turbulent force of the wash fluid around the outside of the transfer probe 172.
  • the wash fluid fills the second well 214 allowing both the inside (e.g., the tube 178, etc.) and the outside (e.g., the support body 176, etc.) of the transfer probe 172 to be washed. As washing operation continues, the wash fluid overflows from the second well 214 into a surrounding gutter 215 and then into the first well 212. for removal.
  • analyzers may include probe assemblies with cleaning stations configured to wash transfer probes and/or wash probes.
  • the pump system 120 of the illustrated analyzer 100 is schematically shown for use in moving fluids through the probe assembly 122 of the analyzer 100.
  • the illustrated system generally includes the four pumps 131 , 132, 133, and 134 (see also FIGS.
  • conduits 218 generally extending between the containers 125, 127, 137, 138, 139, 140, 141 , and 142 and the pumps 131 , 132, 133, and 134 and between the pumps 131 , 132, 133, and 134 and the fluid transfer system 164 and reaction vessel wash system 166, as generally known in the art.
  • a first pump 131 operates to move wash buffer from the wash buffer container 127 to and/or through the dispensing member 194 of the wash probe 190.
  • a second pump 132 operates to aspirate fluid (e.g., wash buffer, samples, reagents, etc.) from a reaction vessel 147 through the aspirating member 196 of the wash probe 190 to the waste container 125.
  • a third pump 133 operates to help transfer, via the transfer probe 172, at least part of a sample from each of the sample vessels to correlated reaction vessels.
  • the third pump 133 operates to help transfer, via the transfer probe 172, a quantity of each reagent (from reagent containers 137, 138, 139, and 140, not shown in FIGS.
  • the third pump 133 also operates to move wash fluid (e.g., wash buffer from the wash buffer container 127, cleaning/rinsing fluids from the containers 141 and 142, etc.) to and/or through the transfer probe 172 during washing, cleaning, etc. operation of the transfer probe 172 (e.g., at the cleaning station 182 of the probe assembly 122, etc.).
  • wash fluid e.g., wash buffer from the wash buffer container 127, cleaning/rinsing fluids from the containers 141 and 142, etc.
  • the third pump 133 operates to help transfer, via the transfer probe 172, a quantity of cleaning/rinsing fluids from the containers 141 and 142 to the reaction vessel wash system 166 (e.g., via the dispensing member 194 of the wash probe 190, etc.) as part of an instrument, self cleaning protocol of the reaction vessel wash system 166 (and wash probe 190).
  • a fourth pump 134 operates to withdraw (e.g., to aspirate, etc.) wash fluid from the cleaning station 182 during operation to wash the transfer probe 172.
  • analyzers may include more than or less than four pumps and/or at least one or more pumps performing operations different from those disclosed herein and/or at least one or more pumps performing multiple (e.g., two or more) operations of the analyzers.
  • the pumps 131 , 132, 133, and 134 of the pump system 120 may include any suitable pump, for example, peristaltic pumps having magnetic home sensors for increasing precision of aspiration and/or dispensing operations.
  • conduits of the pump system 120 may include any suitable conduits, for example, tubing made from polyvinyl chloride (PVC), TEFLON, etc. within the scope of the present disclosure.
  • fluid flow rates and/or movements of the transfer probe 172 and/or wash probe 190 can be controlled (e.g., via the control system 1 10, etc.) to help maximize fluid transfer efficiency, cleaning/washing efficiency, etc.
  • this control can help improve accuracy with which small volumes of the fluid can be delivered reproducibly and repeatedly, for example, by the pumps 131 , 132, 133, and 134 of the pump system 120.
  • the incubation assembly 124 generally includes an outer insulating container 220, an inner insulating container 222 (see also, FIG. 8, etc.), and a cover 224.
  • the inner container 222 is formed as part of the housing's work surface 128. So when the incubation assembly 124 is assembled (see also, FIG. 6, etc.), the outer container 220 is configured to fit generally over the inner container 222 (generally under the work surface 128), and the cover 224 is configured to fit over the inner container 222 (generally above the work surface 128) (see also, FIG. 4, etc.).
  • the outer container 220 may be secured to the inner container 222 by, for example, mechanical fasteners (not shown), or other suitable means.
  • the cover 224 of the illustrated incubation assembly 124 includes a protruded fitting 225 configured to be received by a corresponding fitting 226 of the work surface 128. These fittings 225 and 226 help secure the cover 224 over the inner container 222 and help hold the cover 224 against inadvertent movement off the inner container 222.
  • the protruded fitting 225 of the cover 224 engages with a safety micro-switch of the work surface's fitting 226 so that if the cover 224 is removed/disengaged the micro-switch will disengage and moving parts of the analyzer 100 will stop (e.g., to help inhibit injuries to operators, damage to components of the analyzer 100 (e.g., the probes, etc.), etc.). Similarly, if the cover 224 is not properly positioned over the inner container 222, the micro-switch will not be engaged.
  • the protruded fitting 225 of the cover 224 will not engage the micro-switch of the work surface's fitting 226 (and operation of the analyzer 100 will stop).
  • the cover 224 includes openings 227, 228, and 229 that allow the reaction vessel wash system 166 and the fluid transfer system 164 to access reaction vessels and sample vessels located within the carousel assembly 1 18 (when positioned within the inner container 222) during operation.
  • a first opening 227 allows the transfer probe 172 to access sample vessels
  • a second opening 228 allows the transfer probe 172 to access reaction vessels
  • a third opening 229 allows the wash probe 190 to access reaction vessels.
  • the outer container 220, the inner container 222, and the cover 224 of the incubation assembly 124 provide insulation to help improve thermal performance of the incubation assembly 124 and/or help reduce, for example, heat loss from the incubation assembly 124 during operation.
  • the outer container 220, the inner container 222, and the cover 224 can cooperatively help maintain a temperature within an interior defined by the inner container 222 and the cover 224 (e.g., within which the carousel assembly 1 18 is received, etc.).
  • the outer container 220, the inner container 222, and the cover 224 may be formed from a suitable thermoplastic material such as polycarbonate (PC), acrylonithle butadiene styrene (ABS), etc. using, for example, molds, vacuum forming, selective laser sintering, etc. within the scope of the present disclosure.
  • a temperature control system is provided to control and/or monitor temperature within the incubation assembly 124.
  • the illustrated temperature control system includes a heating system 230 disposed generally within the outer container 220 for use in warming the incubation assembly 124 and providing, for example, an advantageous environment for sample assays to take place (e.g., within the reaction vessels, etc.).
  • the heating system 230 is operable to warm interior regions of the outer and inner containers 220 and 222 and, for example, reaction vessels disposed within the inner container 222.
  • the heating system 230 may also provide for a predefined warming time and/or temperature control time so that the heating system 230 only operates when desired (e.g., based on assay requirements, etc.).
  • analyzers may include temperature control systems that include cooling systems operable for cooling incubation assemblies (and vessels contained therein) as desired.
  • analyzers may include temperature control systems that include both heating and cooling systems.
  • the illustrated heating system 230 generally includes a resistive element 231 (e.g., a resistor, an element heater, etc.) and a fan 232 both positioned toward a perimeter of the outer container 220.
  • the resistive element 231 operates to warm air within the outer and/or inner containers 220 and 222
  • the fan 232 operates to circulate the warmed air through the outer and inner containers 220 and 222.
  • the inner container 222 includes an inlet 234 for allowing warmed air to circulate from the outer container 220 into the inner container 222, and an outlet 235 for allowing air to circulate from the inner container 222 back to the outer container 220.
  • the illustrated heating system 230 can thus circulate warmed air through the outer and inner containers 220 and 222 for warming and/or helping maintain a desired, generally constant temperature (e.g., of the reaction vessels, etc.) within the incubation assembly 124.
  • FIG. 23 illustrates a base support 236 for supporting the probe assembly 122 and the carousel assembly 1 18.
  • the base support 236 couples to the housing 102 in a position generally under the incubation assembly 124 (FIG. 6) for supporting the carousel assembly 1 18 therein.
  • an axle 237 of the base support 236 extends generally upwardly from the base support 236 and through aligned openings 238 and 239 (FIG. 22) of the incubation assembly's outer and inner containers 220 and 222 where it can be received within a support tube 240 (FIG. 13) of the outer carousel 146 when the carousel assembly 1 18 is positioned within the inner container 222.
  • the base support 236 thus helps support rotational movement of the carousel assembly 1 18 (via the axle 237) within the incubation assembly 124.
  • Arms 242 of the base support 236 help support the probe assembly 122 (e.g., via the lower support platform 169 of the probe assembly 122, when coupled to the analyzer's housing 102, etc.), for example, to help position the probe assembly 122 relative to the carousel assembly 1 18.
  • the incubation assembly 124 (and the heating system 230) can operate to incubate reaction vessels received in the carousel assembly 1 18 (and positioned within the incubation assembly 124). It should also be appreciated that in the illustrated incubation assembly 124, the carousel assembly 1 18 is configured such that only the reaction vessels are heated. Wall 157 of the outer carousel 146, which separates the reaction vessels from the sample vessels, also operates to shield the sample vessels from heat produced by the heating system 230 (when the carousel assembly 1 18 is positioned within the incubation assembly 124). Thus, as illustrated, only the reaction vessels are heated. In other example embodiments, sample vessels may be incubated.
  • the reaction vessels can be incubated at, for example, one or more predetermined temperatures.
  • the illustrated incubation assembly 124 can incubate reaction vessels at between about 15 degrees Celsius and about 45 degrees Celsius for an appropriate incubation period. And movement of the carousel assembly 1 18 within the incubation assembly 124 can help maintain a generally even temperature of the reaction vessels within the incubation assembly 124.
  • analyzers may include incubation assemblies capable of incubating reaction vessels, samples, etc. at one or more different temperatures and/or at different temperature ranges. In other example embodiments, analyzers may operate to incubate between about 25 degrees Celsius and about 40 degrees Celsius, and more specifically between about 35 degrees Celsius and about 42 degrees Celsius, for an incubation period of about 15 minutes.
  • Temperature sensors may be included in the incubation assembly 124 to monitor the temperature therein (e.g., to monitor the air temperature within of the incubation assembly 124, etc.).
  • the temperature sensors may be in communication with the control system 1 10 for selectively changing operating parameters of the heating system 230, for example, to help maintain a desired, generally constant temperature of the carousel assembly 1 18, to start heating operation; to stop heating operation etc. (e.g., based on assay requirements, etc.).
  • operation of the analyzer 100 as thus described can promote at least one or more chemical reactions (e.g., as part of one or more various assays, etc.) within the reaction vessels.
  • reagents added to the reaction vessels may promote at least one or more chemical reactions that cause, for example, a color of the samples originally transferred to the reaction vessels to change if the processed samples are positive for a desired trait. If the processed samples are negative for a desired trait, the processed samples may be generally clear.
  • the detection assembly 126 (described next) can then be used to detect, evaluate, analyze, etc. this color (or lack thereof) of the processed samples (e.g., the optical density, color intensity, etc.
  • the detection assembly 126 generally includes a support structure 244 supporting a first detector 246 and a second detector 248.
  • the first and second detectors 246 and 248 are configured to measure transmitted light through a processed sample in a reaction vessel (e.g., the processed fluid in the reaction vessel, etc.) as the reaction vessel passes through a channel 250 of the support structure 244. Maximum absorption occurs when the light transverses the diameter of the reaction vessel.
  • the amount of light measured by the first and second detectors 246 and 248 can then be used, for example, to determine if the processed sample within the reaction vessel contains or does not contain a desired trait (e.g., based on an optical density, color intensity, etc. of the processed sample, etc.).
  • a desired trait e.g., based on an optical density, color intensity, etc. of the processed sample, etc.
  • the detection assembly 126 also helps determine positioning, location, etc. of reaction vessels as they move through and past the detectors 246 and 248 (via the carousel assembly 1 18).
  • optosensors 251 detect flags 252 (FIGS. 1 1-13) around the lower flange 152 of the outer carousel 146 for controlling the position of the carousel assembly 1 18.
  • flags 252 can each have a unique identification corresponding to the respective location on the carousel assembly 1 18 and for indicating position of the carousel assembly 1 18.
  • first and second detectors 246 and 248 can also operate to indicate whether a reaction vessel is present within the detection assembly 126, and then allow for processed samples (e.g., processed samples within reaction vessels, etc.) to be grouped or separated as desired (e.g., by type, etc.) following analysis. For example, if a support vessel opening 148 is left open between groups of processed samples, etc., the sensors can recognize the opening 148 and group the processed samples as desired.
  • processed samples e.g., processed samples within reaction vessels, etc.
  • the second detector 248 (shown in section) of the illustrated detection assembly 126 includes a frame structure 253 supporting a light-emitting diode (LED) 254 (broadly, a light source) and a first lens 255 (e.g., an asphehc lens, etc.) toward a generally inner portion of the support structure 244 (e.g., inwardly of the support structure's channel 250, etc).
  • LED light-emitting diode
  • first lens 255 e.g., an asphehc lens, etc.
  • the frame structure 253 supports a second lens 256 (e.g., an asphehc lens, etc.), a filter 257, and a photodetector 259 (e.g., a phototransistor, etc.) across the channel 250 toward a generally outer portion of the support structure 244 and in general alignment with the LED 254 and first lens 255.
  • a second lens 256 e.g., an asphehc lens, etc.
  • a filter 257 e.g., a filter 257
  • a photodetector 259 e.g., a phototransistor, etc.
  • the structure of the first detector 246 is substantially similar to the structure of the second detector 248.
  • it includes a frame structure 263 supporting a light-emitting diode (LED) 264 (broadly, a light source) and a first lens (e.g., an asphehc lens, etc.) (not visible) toward a generally inner portion of the support structure 244 (e.g., inwardly of the support structure's channel 250, etc).
  • LED light-emitting diode
  • first lens e.g., an asphehc lens, etc.
  • the frame structure 263 supports a second lens (e.g., an asphehc lens, etc.) (not visible), a filter (not visible), and a photodetector (e.g., a phototransistor, etc.) (not visible) across the channel 250 toward a generally outer portion of the support structure 244 and in general alignment with the LED 264 and first lens.
  • a second lens e.g., an asphehc lens, etc.
  • a filter not visible
  • a photodetector e.g., a phototransistor, etc.
  • the detection assembly 126 is positioned generally under the housing 102 and partially within a detection assembly opening 265 (also see FIG. 8) of the insulating assembly's inner container 222.
  • Mechanical fasteners e.g., screws, bolts, etc.
  • the incubation assembly's outer container 220 couples to the work surface 128 and/or inner container 222 generally over the inner container 222, with the detection assembly 126 received generally within the outer container 220 (e.g., generally within portion 267 (FIGS.
  • the lower flange 152 (and its flags 252) (FIG. 12) of the outer carousel 146 is received generally within the channel 250 of the detection assembly's support structure 244.
  • reaction vessels supported by the outer carousel 146 can be positioned, as desired, within the channel 250 for evaluation by the detection assembly 126.
  • the outer carousel 146 selectively moves the reaction vessels positioned therein through the channel 250 and past the first and second detectors 246 and 248 for evaluation.
  • Example operation of the illustrated analyzer 100 will now be described with additional reference to FIGS. 28-30.
  • a desired number of samples (from a desired sample source) are initially collected, for example, within the sample vessels and positioned within the vessel support openings 148 of the inner carousel 144.
  • the sample vessels can each be correlated to the sample sources from which they were taken and, for example, entered into the control system 1 10 of the analyzer 100 (e.g., via the LCD and membrane keypad 1 16, etc.) for subsequent correlation to analysis results of the given samples.
  • Sample vessels containing one or more controls may also be positioned within the vessel support openings 148 of the inner carousel 144, for example, for use in providing a positive and/or negative test result for at least one or more desired trait by the analyzer 100 (other calibrations (e.g., using other prepared standards, etc.) of the analyzer 100 may thus not be necessary). And a corresponding number of reaction vessels are positioned within the vessel support openings 148 of the outer carousel 146.
  • the incubation assembly's cover 224 is positioned over the carousel assembly 1 18 (and on the incubation assembly's inner container 222), and the housing's cover 106 is closed.
  • An operator can then use the LCD and membrane keypad 1 16 to initiate operation of the analyzer 100 (e.g., to input the desired sample information, to select the desired assay parameters, etc.). This activates the probe assembly 122, which moves to a position for transferring at least part of a sample from the sample vessels to correlated reaction vessels.
  • This may also activate the heating system 230 to begin warming reaction vessels in the carousel assembly 1 18 to a desired temperature, for example, of between about 15 degrees Celsius and about 45 degrees Celsius, etc. More particularly, the desired temperature may be between about 25 degrees Celsius and about 45 degrees Celsius. And still more particularly, the desired temperature may be between about 35 degrees Celsius and about 42 degrees Celsius. An incubation time of about 15 minutes may also be provided. The sample vessels are separated from the reaction vessels in the carousel assembly 1 18 by the outer wall 157 of the carousel assembly's inner channel 154 such that only the reaction vessels may be heated. In some example embodiments, incubation assemblies may activate first to achieve a desired temperature before other components of analyzers are activated.
  • the carousel assembly 1 18 initially positions a first sample vessel (not visible) generally under the first opening 227 in the incubation assembly's cover 224, and the transfer probe 172 (via the fluid transfer system 164) moves through the first opening 227 and withdraws at least part of a sample from within the first sample vessel.
  • the carousel assembly 1 18 then rotates (e.g., clockwise, etc.) to position a first reaction vessel (not visible) (correlated to the first sample vessel) generally under the cover's second opening 228.
  • the transfer probe 172 rotates (via the drive mechanism 174 of the fluid transfer system 164) into position generally over the cover's second opening 228, and dispenses the withdrawn sample into the first reaction vessel.
  • the transfer probe 172 rotates to the cleaning station 182 and is cleaned.
  • the carousel assembly 1 18 rotates to position a second sample vessel (not visible) generally under the first opening 227 in the incubation assembly's cover 224.
  • the transfer probe 172 rotates into position generally over the cover's first opening 227, moves through the first opening 228 into the second sample vessel, and withdraws at least part of a sample from within the second sample vessel.
  • the carousel assembly 1 18 then again rotates (e.g., clockwise, etc.) to position a second reaction vessel (correlated to the second sample vessel) generally under the cover's second opening 228.
  • the transfer probe 172 rotates into position generally over the cover's second opening 228, and dispenses the withdrawn sample into the second reaction vessel.
  • the transfer probe 172 then again rotates to the cleaning station 182 and is cleaned.
  • the reaction vessels after receiving samples from their correlated sample vessels, are each incubated (e.g., a first incubation, etc.) within the incubation assembly 124 while the transfer probe 172 continues operation to transfer samples from the remaining sample vessels to their correlated reaction vessels.
  • the reaction vessels incubate (and rotate around the incubation assembly 124 via the carousel assembly 1 18) for about a time required to process (e.g., transfer samples from, etc.) each of the sample vessels contained within the carousel assembly 1 18.
  • the transfer probe 172 receives an additional wash to minimize sample carryover (e.g., to the reagent transfer process, etc.).
  • the additional wash can include washing, for example, with cleaning/rinsing fluid (e.g., from containers 141 and/or 142, etc.) and then rinsing with wash buffer (e.g., at the cleaning station 182, etc.).
  • the carousel assembly 1 18 is approximately positioned with the first reaction vessel generally under the third opening 229 in the incubation assembly's cover 224.
  • the wash probe 190 then operates to move through the third opening 229 (via the drive mechanism 192 of the reaction vessel wash system 166) and into the first reaction vessel.
  • the aspirating member 196 of the wash probe 190 first operates to aspirate any residual fluid from the reaction vessel (to the waste container 125).
  • the dispensing member 194 then operates to dispense wash buffer into the first reaction vessel for washing operation.
  • the aspirating member 196 then again operates to aspirate the wash buffer from the first reaction vessel.
  • the carousel assembly 1 18 rotates to position the second reaction vessel generally under the third opening 229 in the cover 224 so that the wash probe 190 can operate to wash the second reaction vessel. This washing operation continues until each reaction vessel is washed.
  • a set of three wash buffer dispense and aspiration steps are performed by the wash probe 190 for each reaction vessel.
  • Each step uses an increasing amount of wash buffer, for example, up to 1 milliliter, up to 1.5 milliliters, and then up to 1.8 milliliters to minimize splashing.
  • Other numbers of wash steps and other amounts of fluid may be used within the scope of the present disclosure.
  • the carousel assembly 1 18 rotates to position a third reaction vessel generally under the third opening 229 in the cover 224 for washing, it respectively positions the first reaction vessel generally under the cover's second opening 228 for receiving a first reagent via the transfer probe 172.
  • the transfer probe 172 rotates generally over the reagent insert 136 and withdraws (e.g., aspirates, etc.) a first reagent from the first reagent container 137.
  • the transfer probe 172 then rotates over the cover's second opening 228, and transfers the first reagent into the first reaction vessel.
  • the carousel assembly 1 18 then moves the second reaction vessel generally under the cover's second opening 228, and the transfer probe 172 again operates to transfer first reagent into the second reaction vessel.
  • the transfer probe 172 may be cleaned at the cleaning station 182 between each first reagent transfer.
  • reaction vessels after being washed and after receiving the first reagent, again incubate (e.g., a second incubation, etc.) within the incubation assembly 124 while the wash probe 190 continues washing the remaining reaction vessels and while the transfer probe 172 continues transferring first reagent to the remaining reaction vessels.
  • the reaction vessels are allowed to further incubate within the incubation assembly 124 (and rotate there around via the carousel assembly 1 18) for about a time required to process (e.g., wash the reaction vessels, transfer reagent, etc.) each of the reaction vessels. This transfer operation and incubation continues until first reagent is transferred to each of the reaction vessels.
  • the transfer probe 172 may then be cleaned at the cleaning station 182.
  • the carousel assembly 1 18 is again approximately positioned with the first reaction vessel generally under the third opening 229 in the incubation assembly's cover 224.
  • the wash probe 190 again aspirates any residual fluid in the first reaction vessel and then washes the first reaction vessel.
  • the carousel assembly 1 18 rotates to position the second reaction vessel generally under the third opening 229 in the cover 224 so that it can be similarly aspirated and washed.
  • the carousel assembly 1 18 When the carousel assembly 1 18 rotates to position the third reaction vessel generally under the third opening 229 in the cover 224 for washing, it respectively positions the first reaction vessel generally under the cover's second opening 228 for receiving a second reagent via the transfer probe 172 (e.g., from the second reagent container 138, etc.). The carousel assembly 1 18 then moves the second reaction vessel generally under the cover's second opening 228, and the transfer probe 172 again operates to transfer second reagent into the second reaction vessel.
  • the transfer probe 172 e.g., from the second reagent container 138, etc.
  • reaction vessels after being washed and after receiving the second reagent, are further incubated (e.g., a third incubation, etc.) within the incubation assembly 124 while the wash probe 190 continues washing the remaining reaction vessels and while the transfer probe 172 continues transferring second reagent to the remaining reaction vessels. This transfer operation and incubation continues until second reagent is transferred to each of the reaction vessels.
  • operation of the analyzer 100 generally continues until the third reagent is transferred to the reaction vessels.
  • the reaction vessels are again washed (via the wash probe 190), the third reagent is added via the transfer probe 172, and the reaction vessels are incubated.
  • the assay results can be evaluated (e.g., via the detection assembly 126) if a blue color reaction is desired for reading the assay results.
  • a fourth reagent e.g., a stop solution, etc.
  • FIGS. 29A-29C illustrate an example timing diagram 270 for the sample transfer operations and first reagent transfer operations described above (for thirty-two samples).
  • Example operation 271 includes transferring samples from sample vessels to reaction vessels and cleaning the transfer probe 172.
  • Example operation 272 includes incubating (e.g., the first incubation, etc.) the reaction vessels.
  • Example operation 273 includes aspirating and washing the reaction vessels and transferring the first reagent to the reactions vessels.
  • example operation 274 includes incubating (e.g., the second incubation, etc.) the reaction vessels.
  • FIG. 29A also illustrates the overlap of these operations.
  • Example operations for transferring second, third, etc. reagents are not shown, but would be similar to those described for the first reagent. These times are provided merely as example times for the example analyzer 100.
  • reaction vessels may be allowed to incubate for ranges of time between about 5 minutes to about 120 minutes. More particularly, reaction vessels may be allowed to incubate for ranges of time between about 10 minutes and about 30 minutes. And still more particularly, reaction vessels may be allowed to incubate for ranges of time between about 15 minutes and about 20 minutes.
  • the detection assembly 126 When the reaction vessels (and the processed samples therein) are ready to be evaluated (e.g., when ready to read the assay results in the reaction vessels, etc.), the detection assembly 126 is activated. The carousel assembly 1 18 positions the first reaction vessel to move through the detection assembly 126 for a first sample scan. The carousel assembly 1 18 continuously then moves each of the remaining reaction vessels through the detection assembly 126 at a substantially constant speed (e.g., to accommodate for dirt, contamination, etc. on the reaction vessels and/or to optimize positioning of the scan of each reaction vessel, etc.).
  • a substantially constant speed e.g., to accommodate for dirt, contamination, etc. on the reaction vessels and/or to optimize positioning of the scan of each reaction vessel, etc.
  • the wash probe 190 is operated to aspirate the residual fluid from the reaction vessels, wash each of the reaction vessels, and fill them with wash buffer.
  • the carousel assembly 1 18 then moves and presents each of the reaction vessels to the detection assembly 126 for a second background scan.
  • the LED 254 of the first detector 246 is configured to emit light at a first wavelength of about 620 nanometers and the filter 324 is configured to pass light at a corresponding wavelength of about 620 nanometers for subsequent measurement (e.g., density, color intensity, etc.).
  • the first detector 246 operates to provide a first light absorption reading (e.g., as part of the background reading, etc.) associated with variations in the reaction vessel.
  • the LED 314 of the second detector 248 is configured to emit light at a second wavelength of about 450 nanometers and the filter 324 is configured to pass light at a corresponding wavelength of about 450 nanometers for subsequent measurement (e.g., density, color intensity, etc.).
  • the second detector 248 operates to provide a second light absorption reading (e.g., as part of the initial sample reading of the processed sample, etc.).
  • the readings may be taken at the same time, or in stages.
  • analyzers may include detection assemblies having one or more LEDs configured to emit light at one or more different wavelengths and at wavelengths other than 450 nanometers and/or 620 nanometers.
  • the first and/or second detectors 246 and/or 248 may include at least one or more components other than, or in addition to, those disclosed herein within the scope of the present disclosure.
  • the illustrated first and second detectors 246 and 248 operate by sensing the light transmitted through the reaction vessel and the fluid (e.g., wash buffer, processed sample, etc.) contained therein as the reaction vessel moves through the channel 250 and past the detectors 246 and 248. Each detector outputs voltage values indicative of the amount of light being absorbed by the respective detector 246 and 248.
  • the first and second detectors 246 and 248 may broadly be viewed as each measuring an amount of light (e.g., a first amount of light measured by the first detector 246 at a first wavelength and a second amount of light measured by the second detector 248 at a second wavelength, etc.) emitted by the fluid in the reaction vessels.
  • the illustrated detection assembly 126 operates by measuring voltage changes of light across the fluid contained within a reaction vessel for both the background reading (e.g., a first voltage reading from the first detector 246, etc.) and the initial sample reading (e.g., a second voltage reading from the second detector 248, etc.).
  • the background reading (from the first detector 246) and the initial sample reading (from the second detector 248) can then be used to calculate an adjusted (or corrected) sample reading indicative of the actual voltage drop across the fluid in the reaction vessel (and thus indicative of the actual light emitted by the fluid).
  • FIG. 30 illustrates an example voltage line graph 278 produced by the detection assembly 126 during analysis of an example processed sample.
  • the detectors 246 and 248 operate to measure a generally continuous set of voltage values (e.g., to take substantially continuous voltage readings, etc.) across the support structure's channel 250.
  • Graphed line 279 illustrates background voltage values measured by the detection assembly 126
  • graphed line 280 illustrates sample voltage values measured by the detection assembly 126.
  • Roman Numerals I and V indicate areas of measured voltage values respectively before and after a reaction vessel moves past the detectors 246 and 248.
  • the measured voltage values drop when a reaction vessel moves past the detectors 246 and 248 (e.g., at the edges of the reaction vessel as indicated at Roman Numerals Il and IV, etc.). And spikes (or peaks) 281 and 282 are shown (e.g., at Roman Numeral III, etc.) for each graphed line 279 and 280 in connection with the measured voltage values and indicate the measured readings as the light passes through the diameter of the reaction vessel.
  • each reaction vessel (and the fluid contained therein) is scanned two times. For example, each reaction vessel (and the fluid therein) is scanned a first time with both the first and second detectors 246 and 248 to determine a first set of sample readings. The reaction vessel is then aspirated, washed (e.g., with the wash probe 190 of the reaction vessel wash system 166, etc.), filled with wash buffer, and scanned a second time with both the first and second detectors 246 and 248 to determine a second set of background readings. These scans produce two sets of peak voltage values for each of the detectors 246 and 248: a "sample" set for the processed sample, and a "background" set for the reaction vessel containing only wash buffer.
  • the two sets of values can then be used to determine final peak voltage values for use in final absorbance calculations for each of the detectors 246 and 248. This can help reduce erroneous results, for example due to defects (e.g., scratches, etc.) in the reaction vessels.
  • the final measured peak voltage values for each of the first and second detectors 246 and 248 are used to determine absorbance of light by each of the given samples.
  • a ratio is calculated of the peak voltage value measured for the processed sample to the peak voltage value measured for the wash buffer. Then, each ratio is inverted, and the natural log of each of the inverted ratios is calculated.
  • These ratios generally represent absorbance values (e.g., optical densities, color intensities, etc.) for each of the given processed samples (e.g., amounts of light absorbed by each of the given samples, etc.) as measured by each of the first and second detectors 246 and 248 (e.g., at the light wavelengths of about 620 nanometers and about 450 nanometers, respectively, etc.)-
  • an adjusted absorbance value for each of the given samples e.g., a value indicative of a color of each of the given processed samples following reactions thereof, etc.
  • the adjusted absorbance value can then be compared to a predetermine range of absorbance values to determine if the processed sample corresponding to the adjusted absorbance value contains a desired trait.
  • a sample processor is included in the control system 1 10 of the analyzer 100 (e.g., FIG. 3, etc.) to evaluate the measured voltage values from the detection assembly 126 and calculate absorbance values for each of the given processed samples. The processor can then compare the calculated values to predetermined values to determine if the given processed samples contain a desired trait. The control system 1 10 may also correlate the absorbance values to the corresponding tested processed samples for later use (e.g., store the data, etc.), for output to the user, etc. as desired.
  • the illustrated carousel assembly 1 18 can generally incrementally and generally continuously move the sample vessels and reaction vessels around the inner container 222 of the incubation assembly 124 during various operations of the analyzer 100.
  • the carousel assembly 1 18 can generally incrementally and generally continuously move the sample vessels and reaction vessels around the inner container 222 of the incubation assembly 124 during operation of the transfer probe 172 to transfer a sample from each sample vessel to each correlated reaction vessel, during operation of the wash probe 190 to wash each reaction vessel, during operation of the transfer probe 172 to transfer reagents to the reaction vessels, during incubation, etc.
  • This generally incremental and generally continuous movement of the carousel assembly 1 18 during the various operations of the analyzer 100 can help equalize heating of the reaction vessels and may help improve assay results.
  • analyzers may include any combination of one or more components disclosed herein.
  • FIGS. 31 and 32 illustrate an example embodiment of an analyzer 300 including one or more aspects of the present disclosure.
  • the illustrated analyzer 300 generally includes, among other things, a housing 302, a carousel assembly 318 (disposed generally under a cover 424 of an incubation assembly 324), a pump system 320, and a probe assembly 322 for use in analyzing samples for a desired trait.
  • slot indicia 386 of the carousel assembly 318 are printed on an inner carousel 344 of the carousel assembly 318.
  • An outer carousel 346 is free of such indicia.
  • slot indicia may be printed on both inner and outer carousels, on just outer carousels, etc.
  • FIG. 33 illustrates an example embodiment of a kit 590 suitable for use with an analyzer (e.g., 100, 300, etc.).
  • the analyzer may include, for example, an immunoassay analyzer operable to analyze at least one or more samples for a desired trait.
  • the samples may include, for example, blood samples taken from at least one or more animals (e.g., bovine animals such as cows, etc.).
  • the desired trait may include, for example, the presence and/or non-presence of at least one or more PAGs as an indicator of pregnancy.
  • the illustrated kit 590 includes sample vessels 545 each configured to receive a sample to be analyzed by the analyzer for the desired trait and reaction vessels 547 capable of being correlated to respective ones of the sample vessels 545 and configured to receive at least part of the sample from the given sample vessels 545 (via operation of the analyzer) for analysis by the analyzer for the desired trait.
  • Two sample vessels 545A and 545B are provided with controls. One control sample tests positive for a desire trait, and the other control sample tests negative for the desired trait. The control samples may be used to help calibrate the analyzer for the desired trait.
  • the illustrated kit 590 may include any number of sample vessels 545 and reaction vessels 547, for example more than or less than thirty sample vessels and/or more than or less than thirty-two reaction vessels within the scope of the present disclosure.
  • a kit generally includes at least thirty or more sample vessels and/or at least thirty or more reaction vessels.
  • a kit generally includes thirty or less sample vessels and/or thirty or less reaction vessels.
  • the sample vessels 545 may include any suitable sample vessels capable of receiving samples.
  • the sample vessels may include ten milliliter VACUTAINER tubes, or any other suitable vessels within the scope of the present disclosure.
  • Sample vessels may also include, for example, vacuum squeeze bulbs with attachable needles; syringes; any suitable device that can be mounted into a carousel, etc.
  • the reaction vessels 547 may each include any suitable reaction vessel, for example, reaction vessel 147 shown in FIG. 14.
  • the illustrated kit 590 also includes four reagents each contained in respective reagent containers 537, 538, 539, and 540.
  • the reagents are each configured to be added to each of the reaction vessels (e.g., during operation of an analyzer 100, etc.) for reacting with the sample received in each of the reaction vessels.
  • the reagents can help carry out chemical reactions (e.g., ELISA reactions, etc.) involving the samples in each of the reaction vessels.
  • the chemical reactions can help prepare the samples for analysis (e.g., optical analysis, colorimethc analysis, etc.) for a desired trait.
  • kits may include more than or less than four reagents.
  • a kit includes three reagents.
  • the four reagents of the illustrated kit 590 include reagents suitable for use in promoting an ELISA reaction.
  • the illustrated reagents include biotin-labeled anti-pregnancy-associated glycoprotein polyclonal antibody, streptavidin-PolyHRP20, a peroxidase indicator (e.g., a peroxidase substrate, Tetramethylbenzidine, etc.), and a stop solution (e.g., hydrochloric acid, etc.).
  • kits may include reagents suitable for promoting other chemical reactions during operation of analyzers.
  • kits may include at least one or more reagents different from this identified herein.
  • the illustrated kit 590 further includes a wash buffer (e.g., I xPBS with 0.05% Tween20, other suitable wash buffer, etc.) contained within a wash buffer container 527, and cleaning/rinsing solutions (e.g., organic solvents, acids, bases, detergents, etc.) contained within containers 541 and 542.
  • the wash buffer may be used, for example, for washing the reaction vessels.
  • the cleaning/rinsing solutions may be used, for example, for system washing such as probes fluid transfer plumbing, etc.
  • the kit 590 may further include one or more blood collection devices, such as needles, needle holders, etc.
  • kits may include any combination of one or more components disclosed herein.
  • kits may or may not include wash buffer, cleaning solution, etc.
  • an example analyzer including one or more aspects of the present disclosure was used to test blood samples from 29 dairy cows for the presence or non-presence of pregnancy.
  • the analyzer was transported to the dairy and was operated to promote ELISA reactions on samples from 29 dairy cows and then to optically analyze the samples for the presence or non-presence of pregnancy in the cow from which the samples were taken.
  • blood samples were collected from 15 dairy cows that had not been inseminated (non- presence of pregnancy).
  • blood samples were obtained from 14 dairy cows that had been inseminated and had been diagnosed by trans-rectal palpation as having the presence of pregnancy.
  • Table 1 for this example, the analyzer test was negative for the 15 dairy cows that had not been inseminated and l lIII C C C C C NNNN
  • an example analyzer including one or more aspects of the present disclosure was used to test blood samples from dairy cows on a farm for the presence or non-presence of pregnancy. Graphical results of the testing for this example were compiled and are shown in FIG. 34. The blood samples diagnosed as open, shown in diamonds, resulted in an optical density of less than 0.75, whereas the blood samples diagnosed as pregnant, shown in stars, resulted in an optical density of greater than 0.75. Negative and positive controls (shown as squares and circles, respectively) were also run and resulted in optical densities of 0.2 and 3.0 respectively. It should be appreciated that other optical densities may be used as cutoff values for diagnosing open and pregnant cows. In addition, such optical density cutoffs may vary from run to run of the analyzer.
  • an analyzer may be used to test a blood sample from a cow for presence and/or non-presence of pregnancy in the cow.
  • the analyzer is operable to promote an ELISA reaction on the sample and then to optically analyze the sample for presence and/or non-presence of pregnancy in the cow from which the sample was taken.
  • the sample is transferred to a reaction vessel coated with an antibody (e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.).
  • an antibody e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.
  • the analyzer operates to add four reagents to the reaction vessel to promote the ELISA reaction.
  • the reagents include biotin-labeled anti-pregnancy-associated glycoprotein polyclonal antibody, streptavidin-PolyHRP20, a peroxidase indicator (e.g., a peroxidase substrate, Tetramethylbenzidine, etc.), and hydrochloric acid stop solution.
  • the reaction vessel may be washed with a wash buffer including IxPBS with 0.05% Tween20.
  • samples that test positive for pregnancy will have a color. For example, samples may have a blue tint, which may further change color after a stop solution is added (e.g., which may change to a yellow color after a stop solution is added, etc.). And samples that are negative for pregnancy may be clear.
  • the color of the samples can be evaluated, for example, by a detection assembly of the analyzer.
  • an analyzer may be operable to interface directly with a printer (e.g., without requiring use of a control system as described herein, etc.) to provide test results, for example, in a simple printed format.
  • the analyzer may include sufficient memory to store data, for example, for up to five runs of the analyzer.
  • a method for early detection of pregnancy in an animal (e.g., a bovine animal such as a cow, etc.) using an automated analyzer.
  • the method generally includes collecting a sample from an animal in a sample vessel (e.g., a VACUTAINER tube, etc.), and correlating the sample vessel containing the sample to the animal from which the sample was collected (e.g., via a control system of the analyzer, etc.).
  • the sample vessel containing the sample is then positioned within the analyzer along with a reaction vessel such that the reaction vessel is correlated to the sample vessel.
  • the method includes transferring at least part of the sample from the sample vessel to the correlated reaction vessel (for each sample vessel and reaction vessel in the analyzer).
  • a robot probe may be used for transferring at least part of the sample from the sample vessel to the reaction vessel with an automated robot probe.
  • An assay is then performed on the sample in the reaction vessel (e.g., a chemical reaction such as an ELISA reaction, etc.) for each reaction vessel containing a sample in the analyzer.
  • Performing the assay may include, for example, incubating the sample in the reaction vessel, washing the robot probe at a cleaning station (e.g., cleaning station 182, etc.), aspirating at least part of the sample from the reaction vessel with the robot probe, again washing the robot probe at the cleaning station, adding a reagent to the reaction vessel with the robot probe, incubating the reagent in the reaction vessel, again washing the robot probe at the cleaning station, and aspirating at least part of the reagent from the sample vessel with the robot probe.
  • This operation can be repeated by the analyzer for any additional reagents required to perform the desired assay.
  • the samples are tested for presence or non-presence of a desired trait (e.g., presence or non-presence of at least one or more PAGs for indicating pregnancy in the animal, etc.).
  • a desired trait e.g., presence or non-presence of at least one or more PAGs for indicating pregnancy in the animal, etc.
  • the samples may be optically tested using photometric analysis.
  • analyzers may include probe assemblies with transfer probes and/or wash probes moveable in at least one or more of a generally horizontal direction (e.g., generally x-direction, a generally y- direction, etc.), a generally rotational direction, a generally vertical direction (e.g., a generally z-direction, etc.), combinations thereof, etc.
  • a generally horizontal direction e.g., generally x-direction, a generally y- direction, etc.
  • a generally rotational direction e.g., a generally vertical direction, etc.
  • analyzers may include generally stationary carousel assemblies.
  • probe assemblies and/or detection assemblies of the analyzers may be moveable relative to the carousel assemblies during operation of the analyzers for preparing and/or testing the samples for at least one or more desired traits.
  • analyzers may include control systems operable to minimize clogging of probes of the analyzers.
  • the analyzers may include software operable to control power failures and/or other inadvertent interruptions of analyzer operations such that runs of the analyzers involving such failures and/or interruptions would not be lost.
  • analyzers may include detection assemblies configured to perform at least one or more quantitative analysis and/or at least one or more qualitative analysis to determine if given samples contain at least one or more desired traits.
  • an analyzer may be used to promote chemical reactions involving at least one or more samples in reaction vessels.
  • the reaction vessels (and samples therein) are manually inspected (visually) for presence of a color to determine if the samples contain a desired trait generally associated with the color.
  • analyzers may be operable to incubate samples without use of incubation assemblies.
  • incubation of samples may occur as part of the ambient air temperature surrounding the analyzers.
  • analyzers may include cartridge inserts containing at least one or more reagents, wash buffers, cleaning/rinsing fluids, etc. to be used with the analyzers.
  • the cartridge inserts can be replaced for each operational run of the analyzers.
  • Example analyzers of the present disclosure may provide on-farm diagnostic blood test results to identify pregnant and/or non-pregnant bovine animals, such as cows, at least ten to twelve days earlier than industry standard tests (e.g., palpation), with about ninety percent accuracy or better.
  • an analyzer is operable to provide such tests with about ninety-fiver percent or better accuracy.
  • the example analyzers may also be operable to provide on-farm diagnostic blood test results to identify pregnant and/or non-pregnant bovine animals, such as cows, in about four hours or less.
  • an analyzer is operable to provide such results in about two hours or less.
  • the example analyzers may also be operable to provide on-farm diagnostic blood test results to determine if bovine animals, such as cows, are pregnant or non-pregnant within about thirty days or less following breeding.
  • an analyzer is operable to provide such results within about twenty-eight days following breeding.
  • an analyzer is operable to provide such results within about twenty-five days following breeding.
  • Example analyzers of the present disclosure may include detection assemblies operable to analyze a single reaction vessel during operation to test a sample.
  • traditional devices e.g., spectrophotometers, etc.
  • vessels e.g., one for calibration, another for sample analysis, etc.
  • Example analyzers of the present disclosure may also provide inexpensive, rugged, portable, automated, etc. analyzers that can be generally easy to operate, use, maintain, etc.
  • the example analyzers may also include features that help reduce the impact of harsh environments (e.g., dust, temperature/humidity swings, flies, insects, etc.) in which the analyzers may be used (e.g., diary farms, etc.).
  • the example analyzers may include primary covers to cover carousel assemblies within housings of the analyzers, along with separate covers (or lids) to cover sample tubes and/or reaction vessels within the housings.
  • the analyzers may be configured to generally inhibit air intake from outside analyzers.
  • Example analyzers of the present disclosure may further provide for flexibility in testing any number of samples, for example, from one sample to hundreds of samples. Time to process runs of the example analyzers can be reduced because sample processing is generally staggered with reagent transfer, incubation, and reaction vessel washing, which can occur substantially simultaneously as carousel assemblies of the example analyzers operate (e.g., rotate, etc.).
  • probe assemblies of the example analyzers can be configured to wash reaction vessels and transfer fluids substantially simultaneously. For example, wash probes are physically located away from transfer probes such that washing operation can take place substantially simultaneously with fluid transfer operation (e.g., in concert with operation of the carousel assemblies, etc.).
  • Example analyzers of the present disclosure may also be generally compact in construction and comprise generally fully contained analysis systems. For example, all samples, reagents, waste collection, etc. are contained within the analyzers. Moreover, automated cleaning cycles may be programmed into control systems of the analyzers to allow for cleaning operations to occur immediately after last samples are read (e.g., optically analyzed, etc.). When complete, users can discard reagent containers, sample vessels, reaction vessels, etc. and the analyzers will be clean and ready for another run.
  • Example analyzers of the present disclosure may also include at least one or more outputs, alerts, etc. to inform users if environmental conditions move outside desired operating ranges.
  • the example analyzers may include at least one or more outputs, alerts, etc. to inform the users that key operations of the analyzers are complete.

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Abstract

An analyzer for analyzing at least one or more samples for a desired trait, for example, presence and/or non-presence of pregnancy in a cow, etc. The analyzer generally includes a housing, an incubation assembly located at least partially within the housing, a carousel assembly located at least partially within the incubation assembly and movable relative to the incubation assembly, and a probe assembly. The carousel assembly is configured to support a sample vessel and a reaction vessel, and the probe assembly is configured to wash the reaction vessel and transfer a sample contained within the sample vessel to the reaction vessel. The analyzer may also include a detection assembly configured to analyze a processed sample in the reaction vessel for the desired trait.

Description

ANALYZERS AND METHODS RELATED THERETO
FIELD
[0001] The present disclosure relates generally to analyzers. More specifically, the present disclosure relates to automated immunoassay analyzers (and related methods) suitable for performing colohmethc analyses, in-field, to determine, for example, pregnancy in bovine animals.
BACKGROUND
[0002] This section provides background information related to the present disclosure which is not necessarily prior art.
[0003] Analyzing samples for desired traits (e.g., presence and/or non- presence of pregnancy, etc.) is often done in controlled environments such as laboratories. Typically, samples (e.g., blood samples, etc.) are taken from desired subjects (e.g., bovine animals, etc.), transported to controlled environments, processed (e.g., processed to form serum, etc.), assayed (e.g., in microtiter plates, etc.), and then visually evaluated (after they are assayed) to determine if the desired traits are present. Alternatively, the desired subjects may be transported to the controlled environments, where samples are then taken, processed, assayed, and visually evaluated to determine if the desired traits are present.
SUMMARY
[0004] This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features.
[0005] Various aspects of the present disclosure relate generally to analyzers for analyzing at least one or more samples for desired traits. In one example embodiment, an analyzer generally includes a housing, an incubation assembly located at least partially within the housing, a carousel assembly located at least partially within the incubation assembly and movable relative to the incubation assembly, and a probe assembly. The carousel assembly is configured to support a sample vessel and a reaction vessel, and the probe assembly is configured to wash the reaction vessel and transfer a sample contained within the sample vessel to the reaction vessel. [0006] Various aspects of the present disclosure also relate generally to incubation assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits. The incubation assemblies are configured to warm and/or help maintain generally constant temperatures of at least one or more processed samples positioned within the incubation assembly. In one example embodiment, an incubation assembly generally includes a first insulating container defining a generally open interior region capable of receiving at least one or more processed samples to be analyzed for a desired trait, a second insulating container defining a generally open interior region, and a heating system disposed generally within the second insulating container. The first insulating container is disposed at least partially within the generally open interior region of the second insulating container, and the heating system is operable to warm and/or help maintain a generally constant temperature of at least one or more processed samples.
[0007] Various aspects of the present disclosure also relate generally to carousel assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits. In one example embodiment, a carousel assembly generally includes a first carousel configured to support at least one or more sample vessels generally around a perimeter of the first carousel, and a second carousel configured to support at least one or more reaction vessels generally around a perimeter of the second carousel. The first carousel is received at least partially within the second carousel. At least one or more sample vessels and at least one or more reaction vessels are supported by the first and second carousels such that each sample vessel is correlated to a respective one of at least one or more reaction vessels, and such that each sample vessel is positioned radially adjacent its correlated reaction vessel. Each of the one or more reaction vessels is configured to receive at least part of a sample from a correlated one of at least one or more sample vessels for analysis for a desired trait, and whereby each of at least one or more reaction vessels can be readily matched with the sample vessel from which the respective sample was received.
[0008] Various aspects of the present disclosure also relate generally to probe assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits. The immunoassay analyzers support at least one or more sample vessels and at least one or more reaction vessels with each of at least one or more reaction vessels being correlated to each of at least one or more sample vessels. And the probe assemblies are operable to wash each of at least one or more reaction vessels and transfer at least part of a sample contained within each of at least one or more sample vessels to one or more correlated reaction vessels. In one example embodiment, a probe assembly generally includes a support platform configured to be coupled to a work surface of an immunoassay analyzer, a first probe supported by the support platform and configured to generally wash each of at least one or more reaction vessels, a second probe supported by the support platform adjacent the first probe and configured to transfer at least part of a sample contained within each of at least one or more sample vessels to a correlated one of at least one or more reaction vessels, and a cleaning station configured to wash the first and/or second probes.
[0009] Various aspects of the present disclosure also relate generally to detection assemblies for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits. The detection assemblies are operable to determine amounts of light absorbed and/or emitted by each of at least one or more processed samples for use in indicating presence and/or non-presence of the desired traits in each of at least one or more processed samples. In one example embodiment, a detection assembly generally includes a first detector having a light source and a photodetector, and a second detector having a light source and a photodetector. The first detector is configured to measure a first amount of light at a first wavelength passing through each of at least one or more processed samples to be analyzed for a desired trait by an immunoassay analyzer. And the second detector is configured to measure a second amount of light at a second wavelength passing through each of at least one or more processed samples to be analyzed for the desired trait by the immunoassay analyzer. At least one or more processed samples are moved at a generally constant speed past the light source and the photodetector of the first detector and past the light source and the photodetector of the second detector. The light source of the first detector emits light passing through at least one or more of the processed samples, and the photodetector of the first detector measures the amount of light at the first wavelength passing through each of the processed samples. The light source of the second detector emits light passing through at least one or more of the processed samples, and the photodetector of the second detector measures the amount of light at the second wavelength passing through each of the processed samples.
[0010] Various aspects of the present disclosure also relate generally to kits for use with immunoassay analyzers operable to analyze at least one or more samples for desired traits. In one example embodiment, a kit generally includes at least one or more sample vessels configured to receive a sample to be analyzed by an immunoassay analyzer for a desired trait, at least one or more reaction vessels capable of being correlated to at least one or more sample vessels and configured to receive at least part of the sample from at least one or more sample vessels for analysis by the immunoassay analyzer for the desired trait, at least one or more reagents configured to be added to at least one or more reaction vessels for reacting with said at least part of the sample received therein for use in preparing said sample for analysis by the immunoassay analyzer for the desired trait, a wash buffer for use in washing at least one or more reaction vessels before at least one or more sample vessels receive a reagent. At least one or more reaction vessels are generally coated with an antibody.
[0011] Various aspects of the present disclosure also relate generally to methods for early detection of pregnancy in animals using automated analyzers. In one example embodiment, a method generally includes collecting a sample from an animal in a sample vessel, correlating the sample vessel containing the sample to the animal from which the sample was collected, positioning the sample vessel in an automated analyzer, positioning a reaction vessel in the automated analyzer in a position such that the reaction vessel can be correlated to the sample vessel, transferring at least part of the sample from the sample vessel to the reaction vessel, performing an enzyme-linked immuno-sorbent assay on the sample in the reaction vessel to produce a processed sample, and analyzing the processed sample after performing the enzyme-linked immuno-sorbent assay for presence and/or non- presence of at least one or more pregnancy-associated glycoproteins for indicating pregnancy and/or non-pregnancy in the animal.
[0012] Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.
DRAWINGS
[0013] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.
[0014] FIG. 1 is an upper perspective view of an example embodiment of an analyzer including one or more aspects of the present disclosure;
[0015] FIG. 2 is a lower perspective view of the analyzer of FIG. 1 ;
[0016] FIG. 3 is a block diagram of a control system of the analyzer of FIG.
1 ;
[0017] FIG. 4 is the upper perspective view of FIG. 1 with a cover of a housing of the analyzer removed to show internal assemblies and components of the analyzer;
[0018] FIG. 5 is the upper perspective view of FIG. 4 with a cover of an incubation assembly of the analyzer removed to show a carousel assembly of the analyzer positioned generally within the incubation assembly;
[0019] FIG. 6 is a lower perspective view similar to FIG. 2 with the cover of the housing removed and with a base of the housing removed to show internal assemblies and components of the analyzer;
[0020] FIG. 7 is an upper perspective view of a body of the housing of the analyzer of FIG. 1 ;
[0021] FIG. 8 is a lower perspective view of the body of FIG. 7;
[0022] FIG. 9 is a fragmentary perspective view of the analyzer of FIG. 1 illustrating a reagent insert of the analyzer;
[0023] FIG. 10 is a perspective view of containers configured to be supported in the reagent insert of the analyzer of FIG. 9;
[0024] FIG. 1 1 is an exploded perspective view of the carousel assembly of the analyzer of FIG. 1 ;
[0025] FIG. 12 is an upper perspective view of the carousel assembly of FIG. 1 1 assembled; [0026] FIG. 13 is a lower perspective view of the carousel assembly of FIG. 12;
[0027] FIG. 14 is an example reaction vessel suitable for use with the analyzer of FIG. 1 ;
[0028] FIG. 15 is an upper perspective view of a probe assembly of the analyzer of FIG. 1 ;
[0029] FIG. 16 is a lower perspective view of the probe assembly of FIG. 15;
[0030] FIG. 17 is the upper perspective view of FIG. 12 rotated about one- hundred and eighty degrees;
[0031] FIG. 18 is a partially exploded perspective view of the probe assembly of FIG. 15;
[0032] FIG. 19 is a perspective view of a cleaning station of the probe assembly of FIG. 15;
[0033] FIG. 20 is a longitudinal section view of the cleaning station of FIG. 19;
[0034] FIG. 21 A is a schematic of a pump system of the analyzer of FIG. 1 ;
[0035] FIG. 21 B is a schematic similar to FIG. 21 A with a transfer probe of the probe assembly shown rotated;
[0036] FIG. 22 is an exploded perspective view of the incubation assembly of the analyzer of FIG. 1 ;
[0037] FIG. 23 is a perspective view of a base support of the analyzer of FIG. 1 configured to support rotational movement of the carousel assembly during operation of the analyzer;
[0038] FIG. 24 is an upper perspective view of a detection assembly of the analyzer of FIG. 1 ;
[0039] FIG. 25 is a side perspective view of the detection assembly similar to that of FIG. 24 with part of the detection assembly broken away to show internal construction;
[0040] FIG. 26 is a schematic of a detector of the detection assembly of FIG. 24 with example movement of light through the detector shown in broken lines; [0041] FIG. 27 is a bottom perspective view of the body of the housing of the analyzer of FIG. 1 illustrating the detection assembly coupled to an inner container of the incubation assembly;
[0042] FIG. 28 is a top plan view of the analyzer of FIG. 1 with a cover of the housing removed and illustrating example movement of a transfer probe of the probe assembly, with broken lines, during operation of the analyzer;
[0043] FIG. 29A is a schematic of an example assay timing diagram for operation of the analyzer of FIG. 1 ;
[0044] FIG. 29B is an enlarged fragmentary view of the schematic of FIG. 29A illustrating an example timing segment for transferring a sample from a sample vessel to a reaction vessel, using a transfer probe, cleaning the transfer probe, and incubating the reaction vessel;
[0045] FIG. 29B is an enlarged fragmentary view of the schematic of FIG. 29A illustrating an example timing segment for aspirating residual fluid from the reaction vessel, using a wash probe, washing the reaction vessel, adding reagent to the reaction vessel, and incubating the reaction vessel;
[0046] FIG. 30 is an example line graph illustrating example voltage drop across an example processed sample during analysis of the processed sample with the detection assembly of FIG. 24;
[0047] FIG. 31 is an upper perspective view of another example embodiment of an analyzer including one or more aspects of the present disclosure;
[0048] FIG. 32 is an upper perspective view of a carousel assembly of the analyzer of FIG. 31 ;
[0049] FIG. 33 is a schematic of an example kit configured for use with, for example, the example analyzer of FIG. 1 , the example analyzer of FIG. 31 , etc.; and
[0050] FIG. 34 is a graph illustrating graphical results from testing described in Example 2 of the present disclosure.
[0051] Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings.
DETAILED DESCRIPTION
[0052] Example embodiments will now be described more fully with reference to the accompanying drawings. [0053] Example embodiments are provided so that this disclosure will be thorough, and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific components, devices, assemblies, and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.
[0054] The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms "comprises," "comprising," "including," and "having," are inclusive and therefore specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed.
[0055] When an element or layer is referred to as being "on", "engaged to", "connected to" or "coupled to" another element or layer, it may be directly on, engaged, connected or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being "directly on," "directly engaged to", "directly connected to" or "directly coupled to" another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," etc.). As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items. [0056] Although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as "first," "second," and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the example embodiments.
[0057] Spatially relative terms, such as "inner," "outer," "beneath", "below", "lower", "above", "upper" and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. Spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the example term "below" can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
[0058] The present disclosure generally relates to automated analyzers. Example automated analyzers can include, for example, automated immunoassay analyzers configured (e.g., sized, shaped, constructed, etc.) to test at least one or more samples for presence or non-presence of a desired trait. Some example analyzers may be operable to perform enzyme-linked immuno-sorbent assays (ELISAs) on at least one or more samples. Some example analyzers may be operable to test at least one or more biological samples taken from bovine animals for presence of at least one or more pregnancy-associated glycoproteins (PAGs). For example, numerous (e.g., 21 , etc.) PAGs are known and present at different times of bovine gestation, and ELISAs performed by example immunoassay analyzers of the present disclosure can be used in the analyzers to detect, for example, at least one or more PAG isoforms (e.g., five PAG isoforms, etc.) as early as, for example, about day 25 in the bovine gestation cycle to help indicate pregnancy or non-pregnancy of the bovine. Example compositions and methods for detecting early stage pregnancy in, for example, bovine animals is described in co- owned U.S. Provisional Patent Application No. 61/013,603, filed December 13, 2007, the entire disclosure of which is incorporated herein by reference.
[0059] With reference now to the drawings, FIGS. 1-30 illustrate an example embodiment of an analyzer 100 including one or more aspects of the present disclosure. The illustrated analyzer 100 is configured, for example, to test at least one or more samples for a desired trait. Tests may include immunoassay tests (e.g., an enzyme-linked immuno-sorbent assays (ELISA), etc.), and samples may include solid samples (e.g., dry samples to which liquid is later added for analysis, etc.), liquid samples, etc. obtained from any suitable source. For example, liquid samples may include liquid analyte samples such as biological samples (e.g., whole- blood samples, urine samples, saliva samples, milk samples, plasma samples, serum samples, etc.) obtained from one or more animals (e.g., bovine animals, animals from the order Artiodactyla (e.g., ungulates including, but not limited to, camels, horses, deer, cows, goats, pigs, sheep, whales, etc.), etc.). Desired traits may include presence and/or non-presence of at least one or more pregnancy indicators, for example, at least one or more pregnancy-associated glycoproteins (PAGs). Desired traits may also include other pregnancy related factors; presence and/or non-presence of progesterone; presence and/or non-presence of positive energy balance indicators (e.g., blood ketones in cows, etc.), health status indicators (e.g., disease indicators such as for Johnes Disease, etc.); etc.
[0060] The illustrated analyzer 100 is an automated analyzer 100 capable of in-field analysis. For example, biological samples received from one or more cows on a farm can be processed by the analyzer 100 in-field at the farm for presence and/or non-presence of at least one or more PAGs. The samples can be taken directly from the cows (and correlated to the cows from which they are taken), placed into the analyzer 100, and processed in-field at the farm (e.g., without having to send the samples to a lab, etc.). For example, the illustrated analyzer 100 may initially perform an ELISA on each of the samples (e.g., after the samples are transferred from sample vessels to reaction vessels, etc.), and then optically analyze each of the processed samples (e.g., within the reaction vessels, etc.) for the presence and/or non-presence of at least one or more PAGs. A blue colored processed sample (e.g., within a reaction vessel, etc.), following the ELISA, may indicate the presence of at least one or more PAGs in the processed sample (and thus that the cow from which the sample was taken is pregnant); and a clear processed sample (or uncolored processed sample, or faintly colored processed sample, etc.), following the ELISA, may indicate the non-presence of at least one or more PAGs in the processed sample (and thus that the cow from which the sample was taken is not pregnant, or open). Other colors may be used as indicators of presence and/or non-presence of a trait in a processed sample within the scope of the present disclosure. As used herein, processed samples can include samples, fluids, etc. on which an ELISA or other reaction has been performed, for example, in preparation for further analysis. For example, fluid within a reaction vessel following steps of an ELISA or other reaction, etc. can include a processed sample.
[0061] As shown in FIGS. 1 and 2, the analyzer 100 includes a housing 102 having a body 104, a cover 106, and a base 108 (FIG. 2). The cover 106 is coupled to the body 104 by hinges 109 (FIG. 1 ), which allow the cover 106 to pivot relative to the body 104 to selectively open and/or close the cover 106. When the cover 106 is in an open position, for example, samples may be placed into the analyzer 100 for processing; and when the cover 106 is in a closed position, for example, the cover 106 helps protect at least one or more assemblies, other components, etc. of the analyzer 100 located within the housing 102 (and/or samples placed in the analyzer 100 for processing) against ingress of contaminants into the analyzer 100, inadvertent contact during sample processing, etc. The base 108 is coupled to an underside of the body 104 (FIG. 2), for example by mechanical fasteners, etc. (not shown), to help further protect at least one or more assemblies, other components, etc. of the analyzer 100 (and/or samples placed in the analyzer 100 for processing) against ingress of contaminants into the analyzer 100, inadvertent contact during sample processing, etc. Different assemblies of the analyzer 100 located within the housing 102 will be described in further detail hereinafter.
[0062] As diagrammatically shown in FIG. 3, the analyzer 100 also includes a control system 1 10 (e.g., an internal computer system, etc.) for use in controlling and/or operating the analyzer 100. For example, the control system 1 10 can control operation of at least one or more of the assemblies, components, etc. of the analyzer 100 for processing one or more samples placed into the analyzer 100. The control system 1 10 may also enable data storage and data manipulation in connection with sample analysis, as will be described in more detail hereinafter.
[0063] The illustrated control system 1 10 generally includes first and second microcontrollers 1 12 and 1 14 that include, for example, central processing units (CPU), memory, interfaces for communicating with at least one or more of the assemblies, components, etc. of the analyzer 100, sensors, motors, external components (e.g., a PC, a printer, etc.) for monitoring, controlling, reporting, recording, etc. operation of at least one or more of the assemblies, components, etc., and a user interface (e.g., a graphics user interface (GUI), etc.) configured to receive data input and/or display data output in connection with operation of the analyzer 100. The illustrated memory includes software and data for performing various operations and controls of the analyzer 100. For example, the illustrated memory includes software modules such as an operating system; one or more assembly control modules including instructions for operating and controlling at least one or more of the assemblies, components, etc. of the analyzer 100; assay protocols; analyzer self-cleaning and washing protocols; data analysis, processing, and storage modules; expert system support modules; scheduling modules containing instructions and/or data related to scheduling assays and procedures; workflow control; and service support. Memory may include more or less modules than disclosed herein, and/or may include at least one or more different modules than disclosed herein within the scope of the present disclosure. In other example embodiments, control systems may include less than or more than two microcontrollers configured the same or differently than disclosed herein.
[0064] The illustrated control system 1 10 may allow for the analyzer 100 to interface with various different software programs (e.g., spreadsheet programs such as Excel, etc.; dairy management software such as DairyComp 305, etc.; etc.). The software programs may be running on the control system 1 10. Alternatively, the software programs may, for example, be running on at least one or more external control systems such as external personal computers, etc. coupled to the analyzer 100. In addition, the illustrated control system 1 10 may allow for output of test results in at least one or more different data formats, such as, for example, comma- separated values (CSV), etc. In addition, the user interface of the control system 1 10 may allow for easy indexing through, for example, a liquid crystal display (LCD) and membrane keypad 1 16 (FIG. 1 ) (broadly, a user interface).
[0065] With reference again to FIG. 1 , the LCD and membrane keypad 1 16 is positioned generally within the body 104 of the analyzer 100 toward a forward part of the housing 102. A serial bus (e.g., RS232, etc.) 1 17 is provided along a rearward side of the body 104 for attaching at least one or more types of serial peripheral devices (e.g., a printer, etc.). In addition, a universal serial bus (USB, not shown) may be provided for coupling at least one or more types of USB peripheral devices (e.g., a PC, etc.) to the analyzer 100 as desired. In other example embodiments, analyzers may include at least one or more external control systems such as external personal computers, etc. for use in controlling and/or operating the analyzers. The external control systems may allow for connection of additional peripherals to the analyzers including, for example, one or more monitors, keyboards, trackballs, mice, printers, other peripheral input and/or output devices, etc.
[0066] Referring now to FIGS. 4-6, the analyzer 100 generally includes, disposed generally within the housing 102, a carousel assembly 1 18 (FIG. 5), a pump system 120, a probe assembly 122, an incubation assembly 124, and a detection assembly 126 (not visible in FIGS 4-6 but described hereinafter in more detail with reference to FIGS. 24-27). The pump system 120, the probe assembly 122, and the incubation assembly 124 are generally supported by a work surface 128 (FIG. 7, broadly, a platform) located within the housing 102. The probe assembly 122 is positioned adjacent the incubation assembly 124, and the carousel assembly 1 18 and detection assembly 126 are located generally within the incubation assembly 124. A waste container 125 is coupled to the housing 102 outside the analyzer 100 to receive, for example, aspirated waste from the probe assembly 122, etc. And a wash buffer container 127 holding reaction vessel wash fluid is also coupled to the housing 102 outside the analyzer 100.
[0067] As a brief overview, and as will be described in more detail hereinafter, the carousel assembly 1 18 is configured to support at least one or more sample vessels (e.g., sample vessels containing samples, etc.) and at least one or more reaction vessels (e.g., reaction vessels for use in performing assays on the samples, etc.) within the incubation assembly 124. The probe assembly 122 (in operation with the pump system 120 and the carousel assembly 1 18) is configured to transfer at least part of a sample contained within the sample vessels to a correlated one of the reaction vessels for processing, analysis, testing, assay, etc. The probe assembly 122 is also configured to wash at least one or more reaction vessels as desired. The incubation assembly 124 is configured to maintain a temperature of the reaction vessels in the carousel assembly 1 18 (e.g., after a sample is transferred thereto, etc.) and/or to increase and/or to decrease a temperature of (e.g., heat, warm, cool, etc.) the reaction vessels as desired. And the detection assembly 126 is configured to detect presence of color (or lack thereof) in processed samples within the reaction vessels as an indicator of presence and/or non-presence of a desired trait.
[0068] With additional reference to FIGS. 7 and 8, the illustrated work surface 128 of the housing 102 is generally formed as part of the housing's body 104 and includes, for example, an opening 129 for receiving and/or supporting the probe assembly 122, and pump openings 130 for supporting pumps 131 , 132, 133, and 134 (FIGS. 4 and 5) of the pump system 120. For clarity, conduits coupling the pumps, etc. to the probe assembly, etc. are not shown in the drawings.
[0069] With further reference to FIGS. 9 and 10, the illustrated work surface 128 receives and/or supports, within a receptacle 135 of the housing 102 (FIGS. 7 and 8), a reagent insert 136. The reagent insert 136 is configured to hold containers used during operation of the analyzer 100, for example, operation of the pump system 120, the probe assembly 122, etc. The receptacle 135 is defined in the work surface 128 to selectively receive the reagent insert 136 into the housing 102 and/or to selectively allow the reagent insert 136 to be removed from the housing 102. In the illustrated embodiment, the reagent insert 136 is configured to hold four reagent containers 137, 138, 139, 140 and containers 141 and 142 containing system cleaning/rinsing fluids (e.g., water, cleaning solutions, etc.). In other example embodiments, analyzers may include work surfaces and/or reagent inserts configured to hold different numbers of and/or types of containers (e.g., more than or less than four reagent containers, etc.). In still other example embodiments, analyzers may include containers of which all or some are located inside or outside the analyzers. [0070] As shown in FIGS. 1 1 -13, the example carousel assembly 1 18 generally includes an inner carousel 144 configured to hold sample vessels 145 (FIGS. 5 and 1 1 -13) and an outer carousel 146 configured to hold reaction vessels 147 (FIGS. 5 and 1 1-14). Three example sample vessels 145 and three example reaction vessels 147 are shown received in the inner carousel 144 and outer carousel 146, respectively. The inner carousel 144 and the outer carousel 146 each include vessel support openings 148 extending generally around their perimeters for receiving and supporting the sample vessels 145 and reaction vessels 147. For example, the vessel support openings 148 of the inner carousel 144 each include an opening extending through an upper flange 149 of the inner carousel 144 and an aligned recessed opening formed in a lower flange 150 of the inner carousel 144. A sample vessel 145 can be positioned through the opening in the upper flange 149 and into the recessed opening in the lower flange 150 such that the sample vessel 145 is securely supported within the vessel support opening 148 of the inner carousel 144. Similarly, the vessel support openings 148 of the outer carousel 146 include an opening extending through an upper flange 151 of the outer carousel 146 and an aligned recessed opening formed in a lower flange 152 of the outer carousel 146. A reaction vessel 147 can be positioned through the opening in the upper flange 151 and into the recessed opening in the lower flange 152 such that the reaction vessel 147 is securely supported within the vessel support opening 148 of the outer carousel 146.
[0071] When the carousel assembly 1 18 is assembled (FIGS. 12 and 13), the inner carousel 144 is received generally within the outer carousel 146. In the illustrated embodiment, the outer carousel 146 includes an inner channel 154 (FIG. 1 1 ) within which the inner carousel 144 is received. A retaining clip 155 located along an inner portion of the outer carousel's upper flange 151 is received within a notch 156 located along an outer portion of the inner carousel's upper flange 149 to couple (e.g., releasably couple, snap connect, etc.) the inner carousel 144 to the outer carousel 146 within the inner channel 154. In this position, an outer wall 157 of the outer carousel's channel 154 separates the sample vessels 145 supported in the inner carousel 144 from the reaction vessels 147 supported in the outer carousel 146. [0072] A handle 158 is provided generally across an upper portion of the inner carousel 144 such that a user can grasp the handle 158, for example, to move the inner and outer carousels 144 and 146 (e.g., when the inner carousel 144 and outer carousel 146 are coupled together, etc.), to position the carousels 144 and 146 within the incubation assembly 124, to remove the carousels 144 and 146 from the incubation assembly 124, to wash the carousels 144 and 146, etc. as desired.
[0073] With continued reference to FIGS. 12 and 13, the vessel support openings 148 of the illustrated inner and outer carousels 144 and 146 are generally correlated such that each sample vessel 145 received into a vessel support opening 148 of the inner carousel 144 is generally correlated with a respective reaction vessel 147 received into a vessel support opening 148 of the outer carousel 146. And each vessel support opening 148 of the inner carousel 144 is positioned radially adjacent its correlated vessel support opening 148 of the outer carousel 146. In the illustrated embodiment, control fluids are provided in the sample vessels 145 positioned in the sample vessel support openings 148 of the inner carousel 144 identified by the letter indicia "A" and "B".
[0074] The vessel support openings 148 of the inner carousel 144 may be sized differently than the vessel support openings 148 of the outer carousel 146 to help facilitate proper placement of sample vessels 145 in the inner carousel 144 and reaction vessels 147 in the outer carousel 146. For example, the vessel support openings 148 of the inner carousel 144 may be larger than the vessel support openings 148 of the outer carousel 146. And the sample vessels 145 may be sized larger than the reaction vessels 147 (corresponding to the sizes of the vessel support openings 148 in the inner and outer carousels 144 and 146) such that the sample vessels 145 cannot be placed in the vessel support openings 148 of the outer carousel 146. In other example embodiments, vessel support openings of inner carousels may be smaller than vessel support openings of outer carousels, and sample vessels may be sized smaller than reaction vessels (corresponding to the sizes of the vessel support openings in the inner and outer carousels) such that the reaction vessels cannot be placed in the vessel support openings of the inner carousels. In still other example embodiments, tube shape may be used to help position sample vessels and/or reaction vessels in proper openings. [0075] The correlated relationship between the vessel support openings 148 of the inner and outer carousels 144 and 146 (and thus between the sample vessels 145 and reaction vessels 147 received in the inner and outer carousels 144 and 146) can provide for a known relationship between a sample (e.g., a sample received into a sample vessel 145 positioned in the inner carousel 144, etc.) and an assay performed on the sample (e.g., an assay performed in a reaction vessel 147 on at least part of a sample taken from a correlated sample vessel 145, etc.) such that the assay results can be subsequently correlated to the original sample (e.g., via the control system 1 10, etc.). In the illustrated carousel assembly 1 18, the inner carousel 144 includes vessel support openings 148 configured to hold thirty sample vessels 145 and two sample vessels 145 with control fluids, and the outer carousel 146 includes vessel support openings 148 configured to hold thirty-two correlated reaction vessels 147. In other example embodiments, carousel assemblies may be configured to hold more or fewer sample vessels and/or reaction vessels than disclosed herein.
[0076] A drive mechanism (not shown) is provided for conjointly rotating the inner and outer carousels 144 and 146 generally within (and relative to) the incubation assembly 124 during operation of the analyzer 100. For example, a motor can interact with teeth 153 of the outer carousel 146 to rotate the outer carousel 146 (and thus the inner carousel 144 coupled thereto) within the incubation assembly 124.
[0077] FIG. 14 illustrates an example reaction vessel 147 suitable for use with the illustrated analyzer 100. The reaction vessel 147 is generally elongate and tubular in shape, and includes a body 159, an upper open end portion 160, and a lower closed end portion 161. Internal ribs 162 (or fins) are provided within the reaction vessel 147 generally toward the lower closed end portion 161 . Inner surfaces of the illustrated reaction vessel 147 (including the ribs 162) are coated with, for example, an antibody (e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.). For example, the antibody may facilitate or initiate a reaction (e.g., an ELISA reaction, etc.) and capture one or more PAGs which then start to promote the reaction. The ribs 162 may help improve completeness of the reaction within the reaction vessel 147 as the ribs 162 increase surface area in the reaction vessel 147 over which the reactions may take place. In other example embodiments, reaction vessels may include shapes other than disclosed herein, for example rectangular shapes (e.g., cuvettes, etc.), etc. In still other example embodiments, reaction vessels may be coated with at least one or more other antibodies, other materials, or may be free of any coatings. In still further example embodiments, reaction vessels may include other structures to increase surface area within the reaction vessels (e.g., for reactions to occur within the vessels, etc.), such as, for example, grooves, beads, etc. In still other example embodiments, reaction vessels without fins may be used (with or without antibody coatings).
[0078] Sample vessels suitable for use with the illustrated analyzer 100 may include any suitable sample vessels capable of receiving samples. For example, the sample vessels may include VACUTAINER tubes (e.g., ten milliliter VACUTAINER tubes, etc.), or any other suitable vessels within the scope of the present disclosure.
[0079] With reference now to FIGS. 15-18, the example probe assembly 122 of the illustrated analyzer 100 will be described. As shown in FIG. 15, the probe assembly 122 generally includes an automated fluid transfer system 164 and an automated reaction vessel wash system 166. The fluid transfer system 164 operates to transfer a sample (including one or more control fluids) from sample vessels to correlated reaction vessels. The fluid transfer system 164 also operates to transfer at least one or more reagents (e.g., from reagent containers 137, 138, 139, and. /or 140, etc.) to the reaction vessels for generally initiating a reaction on the samples in the reaction vessels as desired. And the reaction vessel wash system 166 operates to wash, clean, etc. at least one or more reaction vessels received within the carousel assembly 1 18, for example, after one or more steps of a reaction within the reaction vessels, etc. In other example embodiments, the fluid transfer system 164 and/or the reaction vessel wash system 166 may be at least partially manual systems.
[0080] The fluid transfer system 164 and the reaction vessel wash system
166 are generally supported along respective first and second guide posts 165 and
167 located between upper and lower support platforms 168 and 169. The platforms
168 and 169 couple the fluid transfer system 164 and reaction vessel wash system 166 to the body 104 and work surface 128 of the analyzer's housing 102. For example, the upper support platform 168 can be coupled to a rearward wall 170 of the body 104, and the lower support platform 169 can be coupled to or integrated into the work surface 128 generally within the work surface's second opening 129. Suitable means may be used to couple the upper support platform 168 to the body 104 and/or the lower support platform 169 to the work surface 128, for example, mechanical fasteners, welds, integral forming means, etc. within the scope of the present disclosure.
[0081] The fluid transfer system 164 generally includes a transfer probe 172 (e.g., an automated robot transfer probe, etc.) for transferring a sample contained within a sample vessel to a correlated reaction vessel, and for then transferring a reagent from a reagent container (e.g., 137, 138, 138, 140, etc.) to the correlated reaction vessel. The fluid transfer system 164 also includes a frame structure 173 supporting the transfer probe 172, and a drive mechanism 174 coupled to the frame structure 173 for moving the frame structure 173 and transfer probe 172 in a generally vertical direction (e.g., a generally z-direction, etc.) and in a generally rotational direction. This generally vertical and generally rotational operation of the transfer probe 172 can help minimize an operational footprint of the probe assembly 122.
[0082] The transfer probe 172 includes a support body 176 and a continuous flexible inner tube 177 extending through the support body 176. The support body 176 and tube 177 couple to a head 178, which in turn couples to the frame structure 173 (e.g., releasably couples thereto via a thumbscrew 181 , etc.). The support body 176 may be formed to help keep the tube 177 generally straight through the support body 176 (e.g., help inhibit inadvertent bending of the tube 177, help protect the tube 177, etc.) during repeated use/operation of the transfer probe 172 (e.g., fluid transfer via the tube 177, etc.). The support body 176 and the tube 177 may be formed from materials that promote easy cleaning, durability, reusability, etc. For example, the support body 176 may be formed from stainless steel, etc., and the tube 177 may be formed from TEFLON, etc. The fluid transfer system 164 can also operate to wash the transfer probe 172 as necessary (e.g., using the system cleaning/rinsing fluids, etc.).
[0083] The frame structure 173 of the fluid transfer system 164 is coupled to the first guide post 165 (e.g., by spherical bearings, etc.) for supporting sliding movement of the frame structure 173 (and transfer probe 172) along the first guide post 165 during operation. This allows the drive mechanism 174 to move the transfer probe 172 (via the frame structure 173) generally vertically into and/or out of sample vessels received within the carousel assembly 1 18, into and/or out of reaction vessels received within the carousel assembly 1 18, and into and/or out of reagent containers (e.g., 137, 138, 138, 140, etc.) supported by the work surface 128. The frame structure 173 is also positioned along the first guide post 165 for supporting rotational movement of the frame structure 173 (and transfer probe 172). This allows the drive mechanism 174 to rotate the transfer probe 172 between sample vessels, reaction vessels, reagent containers (e.g., 137, 138, 138, 140, etc.), and a cleaning station 182 during operation.
[0084] With reference to FIG. 16, the illustrated drive mechanism 174 of the fluid transfer system 164 includes a rack-and-pinion gear drive mechanism to move the transfer probe 172 generally vertically, and a rotational gear drive mechanism to move the transfer probe 172 generally rotationally. The rack-and- pinion gear drive mechanism includes a rack 185 positioned along the frame structure 173 and extending through the lower support platform 169, and a pinion 186 positioned generally under the lower support platform 169 in engagement with the rack 185. A first motor 187 positioned generally under the lower support platform 169 drives the generally linear, vertical movement of the transfer probe 172 (via the rack 185 and pinion 186). A second motor 188 is positioned generally under the lower support platform 169 to rotate the transfer probe 172 via a gear 189.
[0085] With reference now to FIG. 17, the reaction vessel wash system 166 generally includes a wash probe 190 (e.g., an automated robot wash probe, etc.) for washing, cleaning, etc. reaction vessels, a frame structure 191 supporting the wash probe 190, and a drive mechanism 192 coupled to the frame structure 191 for moving the frame structure 191 and wash probe 190 in a generally vertical direction (e.g., a generally z-direction, etc.). This generally vertical operation of the wash probe 190 can help minimize an operational footprint of the probe assembly 122.
[0086] The illustrated wash probe 190 includes a generally dual member structure (e.g., a dual probe-member structure, etc.). It includes a dispensing member 194 (e.g., a dispensing probe member, etc.) and an aspirating member 196 (e.g., an aspirating probe member, etc.) coupled to a head 197, which is releasably coupled to the frame structure 191 (e.g., via a thumbscrew 181 , etc.). The dispensing member 194 includes a support body 198 (or sleeve) and a continuous flexible inner tube 199 extending through the support body 198. The aspirating member 196 includes a support body 202 (or sleeve) and a continuous flexible inner tube 203 extending through the support body 202. The support bodies 198 and 202 of the dispensing member 194 and/or of the aspirating member 196 may be formed to help keep the respective tubes 199 and/or 203 generally straight through the support bodies 198 and 202 (e.g., help inhibit inadvertent bending of the tubes 199 and 203, help protect the tubes 199 and 203, etc.) during repeated use/operation of the wash probe 190 (e.g., fluid transfer via the tubes 199 and/or 203, etc.). The support bodies 198 and 202 and the tubes 199 and 203 of each member 254, 256 may be formed from materials that promote easy cleaning, durability, reusability, etc. For example, the support body 198 of the dispensing member 194 and/or the support body 202 of the aspirating member 196 may be formed from stainless steel, etc., and the tube 199 of the dispensing member 194 and/or the tube 203 of the aspirating member 196 may be formed from TEFLON, etc.
[0087] It should be appreciated that separation of the dispensing member 194 and the aspirating member 196 in the wash probe 190 may help reduce and/or minimize contamination in the reaction vessels during washing operation of the reaction vessels. For example, uncontaminated wash buffer can be introduced (e.g. pumped from the wash buffer container 127 (FIG. 4), etc.) into the reaction vessels for washing by the dispensing member 194, and then aspirated from the reaction vessels by the separate aspirating member 196 (e.g., to the waste container 125 (FIG. 4), etc.). Any reaction residue in the reaction vessel is also aspirated by (and through) the aspirating member 196 separate from the dispensing member 194. So when a subsequent reaction vessel is positioned for washing, aspirated residue from the prior reaction vessel will not inadvertently be dispensed into the subsequent reaction vessel during transfer of wash buffer. In other example embodiments, analyzers may include wash probes in which dispensing functions and aspirating functions are performed by single bodies and/or tubes of the wash probes.
[0088] The frame structure 191 of the reaction vessel wash system 166 is positioned generally along the second guide post 167 for supporting sliding movement of the frame structure 191 (and wash probe 190) along the second guide post 167 during operation. This allows the drive mechanism 192 to move the wash probe 190 (via the frame structure 191 ) generally vertically into and/or out of reaction vessels received within the carousel assembly 1 18 for washing, cleaning, etc. the reaction vessels.
[0089] With additional reference again to FIG. 16, the illustrated drive mechanism 192 of the reaction vessel wash system 166 includes a rack-and-pinion gear drive mechanism to move the wash probe 190 generally vertically. A rack 204 is positioned along a lower part of the frame structure 191 and extends through the lower support platform 169, and a pinion 205 is positioned generally under the lower support platform 169 in engagement with the rack 204. A motor 206 positioned generally under the lower support platform 169 operates to rotate the pinion 205 as desired to drive the generally linear, vertical movement of the wash probe 190 (via the rack 204 and pinion 205).
[0090] As shown in FIG. 18, the frame structure 173 of the illustrated fluid transfer system 164 includes an upper arm 207 to which the head 178 of the transfer probe 172 can be coupled. The frame structure 191 of the illustrated reaction vessel wash system 166 also includes an upper arm 208 to which the head 197 of the wash probe 190 can be coupled. The heads 178 and 197 are removable to help facilitate generally easy replacement of the transfer probe 172 and wash probe 190 if either becomes damaged. Thumbscrews 181 are provided for removably coupling the heads 178 and 197 to the respective upper arms 207 and 208. Further, the frame structure 173 of the fluid transfer system 164 also includes fluid sensors 210 mounted on its upper arm 207 (adjacent the tube 177) for use in controlling dispensing operations of the transfer probe 172. The fluid sensors 210 may also provide indirect means to detect blockage within the transfer probe 172 and/or transfer system 164 (e.g., within the tube 177, other conduits, etc. of the fluid transfer system 164, etc.).
[0091] With additional reference to FIGS. 19 and 20, the cleaning station 182 of the probe assembly 122 is configured to wash, clean, etc. the transfer probe 172 of the fluid transfer system 164 between fluid transfer operations. For example, to help minimize contamination between samples, the transfer probe 172 may be cleaned after each sample transfer from a sample vessel to a reaction vessel, after each reagent transfer to a reaction vessel, etc. In so doing, a tip portion of the transfer probe 172 is positioned within a first, wider well 212 of the cleaning station 182 and wash fluid (e.g., wash buffer from the wash buffer container 127, cleansing/rinsing fluids from the containers 141 and 142, etc.) is dispensed through the transfer probe 172 for internal cleaning. The wash fluid is discharged out of the transfer probe 172 into the first well 212 and transferred (e.g., aspirated via the pump system 120, etc.) through an outlet 213 to the waste container 125 (e.g., via tubing (not shown) coupled to the outlet and waste container 125, etc.). The transfer probe 172 is then moved into a second, narrower well 214 while still dispensing wash fluid. The wash fluid shears up the sides of the second well 214, effectively increasing the turbulent force of the wash fluid around the outside of the transfer probe 172. The wash fluid fills the second well 214 allowing both the inside (e.g., the tube 178, etc.) and the outside (e.g., the support body 176, etc.) of the transfer probe 172 to be washed. As washing operation continues, the wash fluid overflows from the second well 214 into a surrounding gutter 215 and then into the first well 212. for removal. In other example embodiments, analyzers may include probe assemblies with cleaning stations configured to wash transfer probes and/or wash probes.
[0092] Referring to the schematic in FIGS. 21 A and 21 B, the pump system 120 of the illustrated analyzer 100 is schematically shown for use in moving fluids through the probe assembly 122 of the analyzer 100. The illustrated system generally includes the four pumps 131 , 132, 133, and 134 (see also FIGS. 4 and 5) in fluidic communication with the probe assembly 122 (and the various containers 125, 127, 137, 138, 139, 140, 141 , and 142 supported by the housing 102), and conduits 218 generally extending between the containers 125, 127, 137, 138, 139, 140, 141 , and 142 and the pumps 131 , 132, 133, and 134 and between the pumps 131 , 132, 133, and 134 and the fluid transfer system 164 and reaction vessel wash system 166, as generally known in the art.
[0093] As illustrated, a first pump 131 operates to move wash buffer from the wash buffer container 127 to and/or through the dispensing member 194 of the wash probe 190. A second pump 132 operates to aspirate fluid (e.g., wash buffer, samples, reagents, etc.) from a reaction vessel 147 through the aspirating member 196 of the wash probe 190 to the waste container 125. A third pump 133 operates to help transfer, via the transfer probe 172, at least part of a sample from each of the sample vessels to correlated reaction vessels. In addition, the third pump 133 operates to help transfer, via the transfer probe 172, a quantity of each reagent (from reagent containers 137, 138, 139, and 140, not shown in FIGS. 21A and 21 B) to the reaction vessels (e.g., via aspiration, etc.). The third pump 133 also operates to move wash fluid (e.g., wash buffer from the wash buffer container 127, cleaning/rinsing fluids from the containers 141 and 142, etc.) to and/or through the transfer probe 172 during washing, cleaning, etc. operation of the transfer probe 172 (e.g., at the cleaning station 182 of the probe assembly 122, etc.). Further, the third pump 133 operates to help transfer, via the transfer probe 172, a quantity of cleaning/rinsing fluids from the containers 141 and 142 to the reaction vessel wash system 166 (e.g., via the dispensing member 194 of the wash probe 190, etc.) as part of an instrument, self cleaning protocol of the reaction vessel wash system 166 (and wash probe 190). And a fourth pump 134 operates to withdraw (e.g., to aspirate, etc.) wash fluid from the cleaning station 182 during operation to wash the transfer probe 172. In other example embodiments, analyzers may include more than or less than four pumps and/or at least one or more pumps performing operations different from those disclosed herein and/or at least one or more pumps performing multiple (e.g., two or more) operations of the analyzers.
[0094] The pumps 131 , 132, 133, and 134 of the pump system 120 may include any suitable pump, for example, peristaltic pumps having magnetic home sensors for increasing precision of aspiration and/or dispensing operations. And conduits of the pump system 120 may include any suitable conduits, for example, tubing made from polyvinyl chloride (PVC), TEFLON, etc. within the scope of the present disclosure.
[0095] It should be appreciated that fluid flow rates and/or movements of the transfer probe 172 and/or wash probe 190 can be controlled (e.g., via the control system 1 10, etc.) to help maximize fluid transfer efficiency, cleaning/washing efficiency, etc. In addition, this control can help improve accuracy with which small volumes of the fluid can be delivered reproducibly and repeatedly, for example, by the pumps 131 , 132, 133, and 134 of the pump system 120.
[0096] With reference now to FIG. 22, the incubation assembly 124 of the illustrated analyzer 100 will be described. The incubation assembly 124 generally includes an outer insulating container 220, an inner insulating container 222 (see also, FIG. 8, etc.), and a cover 224. In the illustrated embodiment, the inner container 222 is formed as part of the housing's work surface 128. So when the incubation assembly 124 is assembled (see also, FIG. 6, etc.), the outer container 220 is configured to fit generally over the inner container 222 (generally under the work surface 128), and the cover 224 is configured to fit over the inner container 222 (generally above the work surface 128) (see also, FIG. 4, etc.). The outer container 220 may be secured to the inner container 222 by, for example, mechanical fasteners (not shown), or other suitable means.
[0097] The cover 224 of the illustrated incubation assembly 124 includes a protruded fitting 225 configured to be received by a corresponding fitting 226 of the work surface 128. These fittings 225 and 226 help secure the cover 224 over the inner container 222 and help hold the cover 224 against inadvertent movement off the inner container 222. In the illustrated embodiment, the protruded fitting 225 of the cover 224 engages with a safety micro-switch of the work surface's fitting 226 so that if the cover 224 is removed/disengaged the micro-switch will disengage and moving parts of the analyzer 100 will stop (e.g., to help inhibit injuries to operators, damage to components of the analyzer 100 (e.g., the probes, etc.), etc.). Similarly, if the cover 224 is not properly positioned over the inner container 222, the micro-switch will not be engaged. For example, if the sample vessels are not properly positioned in the carousel assembly 1 18, if caps are left on the sample vessels, etc., the protruded fitting 225 of the cover 224 will not engage the micro-switch of the work surface's fitting 226 (and operation of the analyzer 100 will stop).
[0098] Also in the illustrated incubation assembly 124, the cover 224 includes openings 227, 228, and 229 that allow the reaction vessel wash system 166 and the fluid transfer system 164 to access reaction vessels and sample vessels located within the carousel assembly 1 18 (when positioned within the inner container 222) during operation. For example, a first opening 227 allows the transfer probe 172 to access sample vessels; a second opening 228 allows the transfer probe 172 to access reaction vessels; and a third opening 229 allows the wash probe 190 to access reaction vessels. Interaction of the probe assembly 122 with these openings 227, 228, and 229 of the cover 224 will be described hereinafter in connection with example operation of the analyzer 100. [0099] The outer container 220, the inner container 222, and the cover 224 of the incubation assembly 124 provide insulation to help improve thermal performance of the incubation assembly 124 and/or help reduce, for example, heat loss from the incubation assembly 124 during operation. Thus the outer container 220, the inner container 222, and the cover 224 can cooperatively help maintain a temperature within an interior defined by the inner container 222 and the cover 224 (e.g., within which the carousel assembly 1 18 is received, etc.). The outer container 220, the inner container 222, and the cover 224 may be formed from a suitable thermoplastic material such as polycarbonate (PC), acrylonithle butadiene styrene (ABS), etc. using, for example, molds, vacuum forming, selective laser sintering, etc. within the scope of the present disclosure.
[00100] A temperature control system is provided to control and/or monitor temperature within the incubation assembly 124. The illustrated temperature control system includes a heating system 230 disposed generally within the outer container 220 for use in warming the incubation assembly 124 and providing, for example, an advantageous environment for sample assays to take place (e.g., within the reaction vessels, etc.). In particular, the heating system 230 is operable to warm interior regions of the outer and inner containers 220 and 222 and, for example, reaction vessels disposed within the inner container 222. The heating system 230 may also provide for a predefined warming time and/or temperature control time so that the heating system 230 only operates when desired (e.g., based on assay requirements, etc.). A feedback control may also be included to help monitor and/or maintain a desired temperature within the incubation assembly 124. In other example embodiments, analyzers may include temperature control systems that include cooling systems operable for cooling incubation assemblies (and vessels contained therein) as desired. In still other example embodiments, analyzers may include temperature control systems that include both heating and cooling systems.
[00101] The illustrated heating system 230 generally includes a resistive element 231 (e.g., a resistor, an element heater, etc.) and a fan 232 both positioned toward a perimeter of the outer container 220. The resistive element 231 operates to warm air within the outer and/or inner containers 220 and 222, and the fan 232 operates to circulate the warmed air through the outer and inner containers 220 and 222. For example, in the illustrated embodiment the inner container 222 includes an inlet 234 for allowing warmed air to circulate from the outer container 220 into the inner container 222, and an outlet 235 for allowing air to circulate from the inner container 222 back to the outer container 220. The illustrated heating system 230 can thus circulate warmed air through the outer and inner containers 220 and 222 for warming and/or helping maintain a desired, generally constant temperature (e.g., of the reaction vessels, etc.) within the incubation assembly 124.
[00102] FIG. 23 illustrates a base support 236 for supporting the probe assembly 122 and the carousel assembly 1 18. The base support 236 couples to the housing 102 in a position generally under the incubation assembly 124 (FIG. 6) for supporting the carousel assembly 1 18 therein. In this position, an axle 237 of the base support 236 extends generally upwardly from the base support 236 and through aligned openings 238 and 239 (FIG. 22) of the incubation assembly's outer and inner containers 220 and 222 where it can be received within a support tube 240 (FIG. 13) of the outer carousel 146 when the carousel assembly 1 18 is positioned within the inner container 222. The base support 236 thus helps support rotational movement of the carousel assembly 1 18 (via the axle 237) within the incubation assembly 124. Arms 242 of the base support 236 help support the probe assembly 122 (e.g., via the lower support platform 169 of the probe assembly 122, when coupled to the analyzer's housing 102, etc.), for example, to help position the probe assembly 122 relative to the carousel assembly 1 18.
[00103] It should be appreciated that the incubation assembly 124 (and the heating system 230) can operate to incubate reaction vessels received in the carousel assembly 1 18 (and positioned within the incubation assembly 124). It should also be appreciated that in the illustrated incubation assembly 124, the carousel assembly 1 18 is configured such that only the reaction vessels are heated. Wall 157 of the outer carousel 146, which separates the reaction vessels from the sample vessels, also operates to shield the sample vessels from heat produced by the heating system 230 (when the carousel assembly 1 18 is positioned within the incubation assembly 124). Thus, as illustrated, only the reaction vessels are heated. In other example embodiments, sample vessels may be incubated.
[00104] It should also be appreciated that, in the illustrated embodiment, the reaction vessels can be incubated at, for example, one or more predetermined temperatures. For example, the illustrated incubation assembly 124 can incubate reaction vessels at between about 15 degrees Celsius and about 45 degrees Celsius for an appropriate incubation period. And movement of the carousel assembly 1 18 within the incubation assembly 124 can help maintain a generally even temperature of the reaction vessels within the incubation assembly 124. In other example embodiments, analyzers may include incubation assemblies capable of incubating reaction vessels, samples, etc. at one or more different temperatures and/or at different temperature ranges. In other example embodiments, analyzers may operate to incubate between about 25 degrees Celsius and about 40 degrees Celsius, and more specifically between about 35 degrees Celsius and about 42 degrees Celsius, for an incubation period of about 15 minutes.
[00105] Temperature sensors (not shown) may be included in the incubation assembly 124 to monitor the temperature therein (e.g., to monitor the air temperature within of the incubation assembly 124, etc.). The temperature sensors may be in communication with the control system 1 10 for selectively changing operating parameters of the heating system 230, for example, to help maintain a desired, generally constant temperature of the carousel assembly 1 18, to start heating operation; to stop heating operation etc. (e.g., based on assay requirements, etc.).
[00106] At this point it should be appreciated that operation of the analyzer 100 as thus described can promote at least one or more chemical reactions (e.g., as part of one or more various assays, etc.) within the reaction vessels. For example, reagents added to the reaction vessels may promote at least one or more chemical reactions that cause, for example, a color of the samples originally transferred to the reaction vessels to change if the processed samples are positive for a desired trait. If the processed samples are negative for a desired trait, the processed samples may be generally clear. The detection assembly 126 (described next) can then be used to detect, evaluate, analyze, etc. this color (or lack thereof) of the processed samples (e.g., the optical density, color intensity, etc. of the processed samples, etc.) to ultimately determine if the processed samples contain or do not contain the desired trait. In other example embodiments, analyzers may be configured to support assays where no color (or clear colors), following desired reactions, signify presence of a target trait, analyze, etc. [00107] As shown in FIGS. 24-26, the detection assembly 126 generally includes a support structure 244 supporting a first detector 246 and a second detector 248. The first and second detectors 246 and 248 are configured to measure transmitted light through a processed sample in a reaction vessel (e.g., the processed fluid in the reaction vessel, etc.) as the reaction vessel passes through a channel 250 of the support structure 244. Maximum absorption occurs when the light transverses the diameter of the reaction vessel. The amount of light measured by the first and second detectors 246 and 248 can then be used, for example, to determine if the processed sample within the reaction vessel contains or does not contain a desired trait (e.g., based on an optical density, color intensity, etc. of the processed sample, etc.).
[00108] The detection assembly 126 also helps determine positioning, location, etc. of reaction vessels as they move through and past the detectors 246 and 248 (via the carousel assembly 1 18). For example, optosensors 251 detect flags 252 (FIGS. 1 1-13) around the lower flange 152 of the outer carousel 146 for controlling the position of the carousel assembly 1 18. These flags 252 can each have a unique identification corresponding to the respective location on the carousel assembly 1 18 and for indicating position of the carousel assembly 1 18. In addition, the first and second detectors 246 and 248 can also operate to indicate whether a reaction vessel is present within the detection assembly 126, and then allow for processed samples (e.g., processed samples within reaction vessels, etc.) to be grouped or separated as desired (e.g., by type, etc.) following analysis. For example, if a support vessel opening 148 is left open between groups of processed samples, etc., the sensors can recognize the opening 148 and group the processed samples as desired.
[00109] As shown in FIG. 25, and schematically in FIG. 26, the second detector 248 (shown in section) of the illustrated detection assembly 126 includes a frame structure 253 supporting a light-emitting diode (LED) 254 (broadly, a light source) and a first lens 255 (e.g., an asphehc lens, etc.) toward a generally inner portion of the support structure 244 (e.g., inwardly of the support structure's channel 250, etc). The frame structure 253 supports a second lens 256 (e.g., an asphehc lens, etc.), a filter 257, and a photodetector 259 (e.g., a phototransistor, etc.) across the channel 250 toward a generally outer portion of the support structure 244 and in general alignment with the LED 254 and first lens 255. In this position, light emitted by the LED 254 is focused through the first lens 255, passed through the channel 250 (e.g., through a processed sample contained within a reaction vessel moving through the channel 250, etc.), refocused through the second lens 256, passed through the filter 257, and then received by the photodetector 259 for measurement.
[00110] The structure of the first detector 246 is substantially similar to the structure of the second detector 248. For example, it includes a frame structure 263 supporting a light-emitting diode (LED) 264 (broadly, a light source) and a first lens (e.g., an asphehc lens, etc.) (not visible) toward a generally inner portion of the support structure 244 (e.g., inwardly of the support structure's channel 250, etc). The frame structure 263 supports a second lens (e.g., an asphehc lens, etc.) (not visible), a filter (not visible), and a photodetector (e.g., a phototransistor, etc.) (not visible) across the channel 250 toward a generally outer portion of the support structure 244 and in general alignment with the LED 264 and first lens. In this position, as with the first detector 246, light emitted by the LED 264 is focused through the first lens, passed through the channel 250 (e.g., through a processed sample contained within a reaction vessel moving through the channel 250, etc.), refocused through the second lens, passed through the filter, and then received by the photodetector for measurement.
[00111] As shown in FIG. 27, the detection assembly 126 is positioned generally under the housing 102 and partially within a detection assembly opening 265 (also see FIG. 8) of the insulating assembly's inner container 222. Mechanical fasteners (e.g., screws, bolts, etc.) (not shown) may be positioned through openings in wing tabs 266 of the detection assembly's support structure 244 and through corresponding openings (not visible) in the work surface 128 to couple the detection assembly 126 in this position. The incubation assembly's outer container 220 couples to the work surface 128 and/or inner container 222 generally over the inner container 222, with the detection assembly 126 received generally within the outer container 220 (e.g., generally within portion 267 (FIGS. 6 and 22) of the outer container 220, etc.). When the carousel assembly 1 18 is positioned within the inner container 222 of the incubation assembly 124, the lower flange 152 (and its flags 252) (FIG. 12) of the outer carousel 146 (see, e.g., FIG. 13, etc.) is received generally within the channel 250 of the detection assembly's support structure 244. In this position, reaction vessels supported by the outer carousel 146 can be positioned, as desired, within the channel 250 for evaluation by the detection assembly 126. For example, as the carousel assembly 1 18 rotates within the incubation assembly 124, the outer carousel 146 selectively moves the reaction vessels positioned therein through the channel 250 and past the first and second detectors 246 and 248 for evaluation.
[00112] Example operation of the illustrated analyzer 100 will now be described with additional reference to FIGS. 28-30. At the outset, a desired number of samples (from a desired sample source) are initially collected, for example, within the sample vessels and positioned within the vessel support openings 148 of the inner carousel 144. The sample vessels can each be correlated to the sample sources from which they were taken and, for example, entered into the control system 1 10 of the analyzer 100 (e.g., via the LCD and membrane keypad 1 16, etc.) for subsequent correlation to analysis results of the given samples. Sample vessels containing one or more controls may also be positioned within the vessel support openings 148 of the inner carousel 144, for example, for use in providing a positive and/or negative test result for at least one or more desired trait by the analyzer 100 (other calibrations (e.g., using other prepared standards, etc.) of the analyzer 100 may thus not be necessary). And a corresponding number of reaction vessels are positioned within the vessel support openings 148 of the outer carousel 146.
[00113] Once the desired number of sample vessels and reaction vessels are positioned within the carousel assembly 1 18 (e.g., thirty sample vessels containing samples, two sample vessels containing controls, thirty-two reaction vessels, etc.), the incubation assembly's cover 224 is positioned over the carousel assembly 1 18 (and on the incubation assembly's inner container 222), and the housing's cover 106 is closed. An operator can then use the LCD and membrane keypad 1 16 to initiate operation of the analyzer 100 (e.g., to input the desired sample information, to select the desired assay parameters, etc.). This activates the probe assembly 122, which moves to a position for transferring at least part of a sample from the sample vessels to correlated reaction vessels. This may also activate the heating system 230 to begin warming reaction vessels in the carousel assembly 1 18 to a desired temperature, for example, of between about 15 degrees Celsius and about 45 degrees Celsius, etc. More particularly, the desired temperature may be between about 25 degrees Celsius and about 45 degrees Celsius. And still more particularly, the desired temperature may be between about 35 degrees Celsius and about 42 degrees Celsius. An incubation time of about 15 minutes may also be provided. The sample vessels are separated from the reaction vessels in the carousel assembly 1 18 by the outer wall 157 of the carousel assembly's inner channel 154 such that only the reaction vessels may be heated. In some example embodiments, incubation assemblies may activate first to achieve a desired temperature before other components of analyzers are activated.
[00114] With reference to FIG. 28, which illustrates example movement the transfer probe 172, the carousel assembly 1 18 initially positions a first sample vessel (not visible) generally under the first opening 227 in the incubation assembly's cover 224, and the transfer probe 172 (via the fluid transfer system 164) moves through the first opening 227 and withdraws at least part of a sample from within the first sample vessel. The carousel assembly 1 18 then rotates (e.g., clockwise, etc.) to position a first reaction vessel (not visible) (correlated to the first sample vessel) generally under the cover's second opening 228. And the transfer probe 172 rotates (via the drive mechanism 174 of the fluid transfer system 164) into position generally over the cover's second opening 228, and dispenses the withdrawn sample into the first reaction vessel.
[00115] After the first sample is transferred, the transfer probe 172 rotates to the cleaning station 182 and is cleaned. At about the same time, the carousel assembly 1 18 rotates to position a second sample vessel (not visible) generally under the first opening 227 in the incubation assembly's cover 224. The transfer probe 172 rotates into position generally over the cover's first opening 227, moves through the first opening 228 into the second sample vessel, and withdraws at least part of a sample from within the second sample vessel. The carousel assembly 1 18 then again rotates (e.g., clockwise, etc.) to position a second reaction vessel (correlated to the second sample vessel) generally under the cover's second opening 228. And the transfer probe 172 rotates into position generally over the cover's second opening 228, and dispenses the withdrawn sample into the second reaction vessel. The transfer probe 172 then again rotates to the cleaning station 182 and is cleaned. [00116] The reaction vessels, after receiving samples from their correlated sample vessels, are each incubated (e.g., a first incubation, etc.) within the incubation assembly 124 while the transfer probe 172 continues operation to transfer samples from the remaining sample vessels to their correlated reaction vessels. The reaction vessels incubate (and rotate around the incubation assembly 124 via the carousel assembly 1 18) for about a time required to process (e.g., transfer samples from, etc.) each of the sample vessels contained within the carousel assembly 1 18. This transfer operation and incubation continues until samples from each of the sample vessels are transferred to each of their correlated reaction vessels. After transfer of the last sample, the transfer probe 172 receives an additional wash to minimize sample carryover (e.g., to the reagent transfer process, etc.). The additional wash can include washing, for example, with cleaning/rinsing fluid (e.g., from containers 141 and/or 142, etc.) and then rinsing with wash buffer (e.g., at the cleaning station 182, etc.).
[00117] After samples are transferred from each of the sample vessels to their correlated reaction vessels, the carousel assembly 1 18 is approximately positioned with the first reaction vessel generally under the third opening 229 in the incubation assembly's cover 224. The wash probe 190 then operates to move through the third opening 229 (via the drive mechanism 192 of the reaction vessel wash system 166) and into the first reaction vessel. The aspirating member 196 of the wash probe 190 first operates to aspirate any residual fluid from the reaction vessel (to the waste container 125). The dispensing member 194 then operates to dispense wash buffer into the first reaction vessel for washing operation. The aspirating member 196 then again operates to aspirate the wash buffer from the first reaction vessel. After the first reaction vessel is washed, the carousel assembly 1 18 rotates to position the second reaction vessel generally under the third opening 229 in the cover 224 so that the wash probe 190 can operate to wash the second reaction vessel. This washing operation continues until each reaction vessel is washed.
[00118] In the example embodiment, a set of three wash buffer dispense and aspiration steps are performed by the wash probe 190 for each reaction vessel. Each step uses an increasing amount of wash buffer, for example, up to 1 milliliter, up to 1.5 milliliters, and then up to 1.8 milliliters to minimize splashing. Other numbers of wash steps and other amounts of fluid may be used within the scope of the present disclosure.
[00119] When the carousel assembly 1 18 rotates to position a third reaction vessel generally under the third opening 229 in the cover 224 for washing, it respectively positions the first reaction vessel generally under the cover's second opening 228 for receiving a first reagent via the transfer probe 172. The transfer probe 172 rotates generally over the reagent insert 136 and withdraws (e.g., aspirates, etc.) a first reagent from the first reagent container 137. The transfer probe 172 then rotates over the cover's second opening 228, and transfers the first reagent into the first reaction vessel. The carousel assembly 1 18 then moves the second reaction vessel generally under the cover's second opening 228, and the transfer probe 172 again operates to transfer first reagent into the second reaction vessel. The transfer probe 172 may be cleaned at the cleaning station 182 between each first reagent transfer.
[00120] The reaction vessels, after being washed and after receiving the first reagent, again incubate (e.g., a second incubation, etc.) within the incubation assembly 124 while the wash probe 190 continues washing the remaining reaction vessels and while the transfer probe 172 continues transferring first reagent to the remaining reaction vessels. The reaction vessels are allowed to further incubate within the incubation assembly 124 (and rotate there around via the carousel assembly 1 18) for about a time required to process (e.g., wash the reaction vessels, transfer reagent, etc.) each of the reaction vessels. This transfer operation and incubation continues until first reagent is transferred to each of the reaction vessels. The transfer probe 172 may then be cleaned at the cleaning station 182.
[00121] After each of the reaction vessels are washed, filled with first reagent, and incubated, the carousel assembly 1 18 is again approximately positioned with the first reaction vessel generally under the third opening 229 in the incubation assembly's cover 224. The wash probe 190 again aspirates any residual fluid in the first reaction vessel and then washes the first reaction vessel. The carousel assembly 1 18 rotates to position the second reaction vessel generally under the third opening 229 in the cover 224 so that it can be similarly aspirated and washed. When the carousel assembly 1 18 rotates to position the third reaction vessel generally under the third opening 229 in the cover 224 for washing, it respectively positions the first reaction vessel generally under the cover's second opening 228 for receiving a second reagent via the transfer probe 172 (e.g., from the second reagent container 138, etc.). The carousel assembly 1 18 then moves the second reaction vessel generally under the cover's second opening 228, and the transfer probe 172 again operates to transfer second reagent into the second reaction vessel.
[00122] The reaction vessels, after being washed and after receiving the second reagent, are further incubated (e.g., a third incubation, etc.) within the incubation assembly 124 while the wash probe 190 continues washing the remaining reaction vessels and while the transfer probe 172 continues transferring second reagent to the remaining reaction vessels. This transfer operation and incubation continues until second reagent is transferred to each of the reaction vessels.
[00123] In the illustrated embodiment, operation of the analyzer 100 generally continues until the third reagent is transferred to the reaction vessels. For example, the reaction vessels are again washed (via the wash probe 190), the third reagent is added via the transfer probe 172, and the reaction vessels are incubated. At this time, the assay results (within the reaction vessels) can be evaluated (e.g., via the detection assembly 126) if a blue color reaction is desired for reading the assay results. However, if the reaction is desired to be stopped, then a fourth reagent (e.g., a stop solution, etc.) (from the fourth reagent container 140) is added to the reaction vessels without aspirating the previous reagent.
[00124] FIGS. 29A-29C illustrate an example timing diagram 270 for the sample transfer operations and first reagent transfer operations described above (for thirty-two samples). Example operation 271 includes transferring samples from sample vessels to reaction vessels and cleaning the transfer probe 172. Example operation 272 includes incubating (e.g., the first incubation, etc.) the reaction vessels. Example operation 273 includes aspirating and washing the reaction vessels and transferring the first reagent to the reactions vessels. And example operation 274 includes incubating (e.g., the second incubation, etc.) the reaction vessels. In the illustrated diagram, for example, example operation 271 may take about thirty seconds for each sample; example operation 272 may take about sixteen minutes for each sample; example operation 273 may take about thirty seconds for each sample; and example operation 274 may take about sixteen minutes for each sample. FIG. 29A also illustrates the overlap of these operations. Example operations for transferring second, third, etc. reagents are not shown, but would be similar to those described for the first reagent. These times are provided merely as example times for the example analyzer 100.
[00125] In other example embodiments, reaction vessels may be allowed to incubate for ranges of time between about 5 minutes to about 120 minutes. More particularly, reaction vessels may be allowed to incubate for ranges of time between about 10 minutes and about 30 minutes. And still more particularly, reaction vessels may be allowed to incubate for ranges of time between about 15 minutes and about 20 minutes.
[00126] When the reaction vessels (and the processed samples therein) are ready to be evaluated (e.g., when ready to read the assay results in the reaction vessels, etc.), the detection assembly 126 is activated. The carousel assembly 1 18 positions the first reaction vessel to move through the detection assembly 126 for a first sample scan. The carousel assembly 1 18 continuously then moves each of the remaining reaction vessels through the detection assembly 126 at a substantially constant speed (e.g., to accommodate for dirt, contamination, etc. on the reaction vessels and/or to optimize positioning of the scan of each reaction vessel, etc.). Once each of the reaction vessels (and the processed samples therein) are scanned, the wash probe 190 is operated to aspirate the residual fluid from the reaction vessels, wash each of the reaction vessels, and fill them with wash buffer. The carousel assembly 1 18 then moves and presents each of the reaction vessels to the detection assembly 126 for a second background scan.
[00127] The LED 254 of the first detector 246 is configured to emit light at a first wavelength of about 620 nanometers and the filter 324 is configured to pass light at a corresponding wavelength of about 620 nanometers for subsequent measurement (e.g., density, color intensity, etc.). The first detector 246 operates to provide a first light absorption reading (e.g., as part of the background reading, etc.) associated with variations in the reaction vessel. The LED 314 of the second detector 248 is configured to emit light at a second wavelength of about 450 nanometers and the filter 324 is configured to pass light at a corresponding wavelength of about 450 nanometers for subsequent measurement (e.g., density, color intensity, etc.). The second detector 248 operates to provide a second light absorption reading (e.g., as part of the initial sample reading of the processed sample, etc.). The readings may be taken at the same time, or in stages. In other example embodiments, analyzers may include detection assemblies having one or more LEDs configured to emit light at one or more different wavelengths and at wavelengths other than 450 nanometers and/or 620 nanometers. And the first and/or second detectors 246 and/or 248 may include at least one or more components other than, or in addition to, those disclosed herein within the scope of the present disclosure.
[00128] The illustrated first and second detectors 246 and 248 operate by sensing the light transmitted through the reaction vessel and the fluid (e.g., wash buffer, processed sample, etc.) contained therein as the reaction vessel moves through the channel 250 and past the detectors 246 and 248. Each detector outputs voltage values indicative of the amount of light being absorbed by the respective detector 246 and 248. Thus, the first and second detectors 246 and 248 may broadly be viewed as each measuring an amount of light (e.g., a first amount of light measured by the first detector 246 at a first wavelength and a second amount of light measured by the second detector 248 at a second wavelength, etc.) emitted by the fluid in the reaction vessels.
[00129] More specifically, the illustrated detection assembly 126 operates by measuring voltage changes of light across the fluid contained within a reaction vessel for both the background reading (e.g., a first voltage reading from the first detector 246, etc.) and the initial sample reading (e.g., a second voltage reading from the second detector 248, etc.). The background reading (from the first detector 246) and the initial sample reading (from the second detector 248) can then be used to calculate an adjusted (or corrected) sample reading indicative of the actual voltage drop across the fluid in the reaction vessel (and thus indicative of the actual light emitted by the fluid).
[00130] FIG. 30 illustrates an example voltage line graph 278 produced by the detection assembly 126 during analysis of an example processed sample. The detectors 246 and 248 operate to measure a generally continuous set of voltage values (e.g., to take substantially continuous voltage readings, etc.) across the support structure's channel 250. Graphed line 279 illustrates background voltage values measured by the detection assembly 126, and graphed line 280 illustrates sample voltage values measured by the detection assembly 126. Roman Numerals I and V indicate areas of measured voltage values respectively before and after a reaction vessel moves past the detectors 246 and 248. The measured voltage values drop when a reaction vessel moves past the detectors 246 and 248 (e.g., at the edges of the reaction vessel as indicated at Roman Numerals Il and IV, etc.). And spikes (or peaks) 281 and 282 are shown (e.g., at Roman Numeral III, etc.) for each graphed line 279 and 280 in connection with the measured voltage values and indicate the measured readings as the light passes through the diameter of the reaction vessel.
[00131] Further, each reaction vessel (and the fluid contained therein) is scanned two times. For example, each reaction vessel (and the fluid therein) is scanned a first time with both the first and second detectors 246 and 248 to determine a first set of sample readings. The reaction vessel is then aspirated, washed (e.g., with the wash probe 190 of the reaction vessel wash system 166, etc.), filled with wash buffer, and scanned a second time with both the first and second detectors 246 and 248 to determine a second set of background readings. These scans produce two sets of peak voltage values for each of the detectors 246 and 248: a "sample" set for the processed sample, and a "background" set for the reaction vessel containing only wash buffer. The two sets of values can then be used to determine final peak voltage values for use in final absorbance calculations for each of the detectors 246 and 248. This can help reduce erroneous results, for example due to defects (e.g., scratches, etc.) in the reaction vessels.
[00132] After each of the reaction vessels (and the fluids contained therein) are scanned, the final measured peak voltage values for each of the first and second detectors 246 and 248 are used to determine absorbance of light by each of the given samples. For each of the first and second detectors 246 and 248, a ratio is calculated of the peak voltage value measured for the processed sample to the peak voltage value measured for the wash buffer. Then, each ratio is inverted, and the natural log of each of the inverted ratios is calculated. These ratios generally represent absorbance values (e.g., optical densities, color intensities, etc.) for each of the given processed samples (e.g., amounts of light absorbed by each of the given samples, etc.) as measured by each of the first and second detectors 246 and 248 (e.g., at the light wavelengths of about 620 nanometers and about 450 nanometers, respectively, etc.)- Finally, an adjusted absorbance value for each of the given samples (e.g., a value indicative of a color of each of the given processed samples following reactions thereof, etc.) is calculated by subtracting the absorbance value measured by the first detector 246 from the absorbance value measured by the second detector 248. The adjusted absorbance value can then be compared to a predetermine range of absorbance values to determine if the processed sample corresponding to the adjusted absorbance value contains a desired trait.
[00133] In the illustrated embodiment, a sample processor is included in the control system 1 10 of the analyzer 100 (e.g., FIG. 3, etc.) to evaluate the measured voltage values from the detection assembly 126 and calculate absorbance values for each of the given processed samples. The processor can then compare the calculated values to predetermined values to determine if the given processed samples contain a desired trait. The control system 1 10 may also correlate the absorbance values to the corresponding tested processed samples for later use (e.g., store the data, etc.), for output to the user, etc. as desired.
[00134] The illustrated carousel assembly 1 18 can generally incrementally and generally continuously move the sample vessels and reaction vessels around the inner container 222 of the incubation assembly 124 during various operations of the analyzer 100. For example, the carousel assembly 1 18 can generally incrementally and generally continuously move the sample vessels and reaction vessels around the inner container 222 of the incubation assembly 124 during operation of the transfer probe 172 to transfer a sample from each sample vessel to each correlated reaction vessel, during operation of the wash probe 190 to wash each reaction vessel, during operation of the transfer probe 172 to transfer reagents to the reaction vessels, during incubation, etc. This generally incremental and generally continuous movement of the carousel assembly 1 18 during the various operations of the analyzer 100 can help equalize heating of the reaction vessels and may help improve assay results.
[00135] In other example embodiments, analyzers may include any combination of one or more components disclosed herein.
[00136] FIGS. 31 and 32 illustrate an example embodiment of an analyzer 300 including one or more aspects of the present disclosure. The illustrated analyzer 300 generally includes, among other things, a housing 302, a carousel assembly 318 (disposed generally under a cover 424 of an incubation assembly 324), a pump system 320, and a probe assembly 322 for use in analyzing samples for a desired trait. In this embodiment, slot indicia 386 of the carousel assembly 318 are printed on an inner carousel 344 of the carousel assembly 318. An outer carousel 346 is free of such indicia. In other example embodiments, slot indicia may be printed on both inner and outer carousels, on just outer carousels, etc.
[00137] FIG. 33 illustrates an example embodiment of a kit 590 suitable for use with an analyzer (e.g., 100, 300, etc.). The analyzer may include, for example, an immunoassay analyzer operable to analyze at least one or more samples for a desired trait. The samples may include, for example, blood samples taken from at least one or more animals (e.g., bovine animals such as cows, etc.). And the desired trait may include, for example, the presence and/or non-presence of at least one or more PAGs as an indicator of pregnancy.
[00138] The illustrated kit 590 includes sample vessels 545 each configured to receive a sample to be analyzed by the analyzer for the desired trait and reaction vessels 547 capable of being correlated to respective ones of the sample vessels 545 and configured to receive at least part of the sample from the given sample vessels 545 (via operation of the analyzer) for analysis by the analyzer for the desired trait. Two sample vessels 545A and 545B are provided with controls. One control sample tests positive for a desire trait, and the other control sample tests negative for the desired trait. The control samples may be used to help calibrate the analyzer for the desired trait. The illustrated kit 590 may include any number of sample vessels 545 and reaction vessels 547, for example more than or less than thirty sample vessels and/or more than or less than thirty-two reaction vessels within the scope of the present disclosure. For example, in one example embodiment a kit generally includes at least thirty or more sample vessels and/or at least thirty or more reaction vessels. In another example embodiment, a kit generally includes thirty or less sample vessels and/or thirty or less reaction vessels.
[00139] The sample vessels 545 may include any suitable sample vessels capable of receiving samples. For example, the sample vessels may include ten milliliter VACUTAINER tubes, or any other suitable vessels within the scope of the present disclosure. Sample vessels may also include, for example, vacuum squeeze bulbs with attachable needles; syringes; any suitable device that can be mounted into a carousel, etc. The reaction vessels 547 may each include any suitable reaction vessel, for example, reaction vessel 147 shown in FIG. 14.
[00140] The illustrated kit 590 also includes four reagents each contained in respective reagent containers 537, 538, 539, and 540. The reagents are each configured to be added to each of the reaction vessels (e.g., during operation of an analyzer 100, etc.) for reacting with the sample received in each of the reaction vessels. The reagents can help carry out chemical reactions (e.g., ELISA reactions, etc.) involving the samples in each of the reaction vessels. The chemical reactions can help prepare the samples for analysis (e.g., optical analysis, colorimethc analysis, etc.) for a desired trait. In other example embodiments, kits may include more than or less than four reagents. In one example embodiment, a kit includes three reagents.
[00141] The four reagents of the illustrated kit 590 include reagents suitable for use in promoting an ELISA reaction. For example, the illustrated reagents include biotin-labeled anti-pregnancy-associated glycoprotein polyclonal antibody, streptavidin-PolyHRP20, a peroxidase indicator (e.g., a peroxidase substrate, Tetramethylbenzidine, etc.), and a stop solution (e.g., hydrochloric acid, etc.). In other example embodiments, kits may include reagents suitable for promoting other chemical reactions during operation of analyzers. In still other example embodiments, kits may include at least one or more reagents different from this identified herein.
[00142] With continued reference to FIG. 33, the illustrated kit 590 further includes a wash buffer (e.g., I xPBS with 0.05% Tween20, other suitable wash buffer, etc.) contained within a wash buffer container 527, and cleaning/rinsing solutions (e.g., organic solvents, acids, bases, detergents, etc.) contained within containers 541 and 542. The wash buffer may be used, for example, for washing the reaction vessels. And the cleaning/rinsing solutions may be used, for example, for system washing such as probes fluid transfer plumbing, etc.
[00143] The kit 590 may further include one or more blood collection devices, such as needles, needle holders, etc.
[00144] In other example embodiments, kits may include any combination of one or more components disclosed herein. For example, kits may or may not include wash buffer, cleaning solution, etc. EXAMPLES
[00145] The following example is merely illustrative, and not limiting to the disclosure in any way.
Example 1
[00146] In one example, an example analyzer including one or more aspects of the present disclosure was used to test blood samples from 29 dairy cows for the presence or non-presence of pregnancy. In this example the analyzer was transported to the dairy and was operated to promote ELISA reactions on samples from 29 dairy cows and then to optically analyze the samples for the presence or non-presence of pregnancy in the cow from which the samples were taken. In the example, blood samples were collected from 15 dairy cows that had not been inseminated (non- presence of pregnancy). And blood samples were obtained from 14 dairy cows that had been inseminated and had been diagnosed by trans-rectal palpation as having the presence of pregnancy. As shown in Table 1 , for this example, the analyzer test was negative for the 15 dairy cows that had not been inseminated and llIII C C C CNNNN
K K K)))acked the presence of pregnancy. As also shown in Table 1 , the analyzer test was positive for the 14 dairy cows that had been inseminated and had been diagnosed by trans-rectal palpation as having the presence of pregnancy. In Table 1 , the follow abbreviations are used: DCC, days carried calf; DIM, days in milk; Lact #, lactation number; open, not pregnant; preg, pregnant; and CDP, concept demonstration prototype analyzer result. Table 1
Examples of 15 cows that were not inseminated and (non-presence of pregnancy)
Breed CDP
ID Fresh Date Date DCC DIM Lact # Results
4965 06/16/2008 n/a n/a 57 open
5742 06/09/2008 n/a n/a 64 5 open
5745 06/23/2008 n/a n/a 50 4 open
6060 06/21/2008 n/a n/a 52 open
6065 06/09/2008 n/a n/a 64 open
6070 06/13/2008 n/a n/a 60 open
61 12 06/25/2008 n/a n/a 48 open
61 17 06/06/2008 n/a n/a 67 open
6203 06/25/2008 n/a n/a 48 open
6233 06/13/2008 n/a n/a 60 2 open 6384 06/14/2008 n/a n/a 59 1 open
6433 06/25/2008 n/a n/a 48 1 open
6989 06/1 1/2008 n/a n/a 62 1 open
6999 06/23/2008 n/a n/a 50 1 open
8271 06/15/2008 n/a n/a 58 1 open
Examples of 14 cows that were inseminated and were diagnosed by trans-rectal palpation as being pregnant
Breed CDP
ID Fresh Date Date DCC DIM Lact # Results
3281 1 1/9/2007 06/02/2008 70 276 4 preg
4835 09/22/2007 06/13/2008 59 324 2 preg
4957 1 1/23/2007 06/20/2008 52 262 2 preg
5214 06/16/2007 05/25/2008 78 422 preg
5458 12/28/2007 06/12/2008 60 227 4 preg
5533 04/04/2008 06/12/2008 60 129 1 preg
5608 10/1 1/2007 06/18/2008 54 305 preg
5750 12/26/2007 06/27/2008 45 229 1 preg
6214 04/1 1/2008 06/19/2008 53 122 1 preg
6243 01/04/2008 07/01/2008 41 220 1 preg
6306 04/04/2008 06/12/2008 60 129 1 preg
6410 04/08/2008 06/12/2008 60 125 1 preg
6469 03/21/2008 05/29/2008 74 143 ll C CNN 1 preg
7013 03/27/2008 06/05/2008 67 137 1 preg
Example 2
[00147] In another example, an example analyzer including one or more aspects of the present disclosure was used to test blood samples from dairy cows on a farm for the presence or non-presence of pregnancy. Graphical results of the testing for this example were compiled and are shown in FIG. 34. The blood samples diagnosed as open, shown in diamonds, resulted in an optical density of less than 0.75, whereas the blood samples diagnosed as pregnant, shown in stars, resulted in an optical density of greater than 0.75. Negative and positive controls (shown as squares and circles, respectively) were also run and resulted in optical densities of 0.2 and 3.0 respectively. It should be appreciated that other optical densities may be used as cutoff values for diagnosing open and pregnant cows. In addition, such optical density cutoffs may vary from run to run of the analyzer.
[00148] In another example embodiment, an analyzer may be used to test a blood sample from a cow for presence and/or non-presence of pregnancy in the cow. In this embodiment, for example, the analyzer is operable to promote an ELISA reaction on the sample and then to optically analyze the sample for presence and/or non-presence of pregnancy in the cow from which the sample was taken. During operation of the analyzer, the sample is transferred to a reaction vessel coated with an antibody (e.g., a monoclonal antibody such as a monoclonal 2D9 antibody, a polyclonal antibody that recognizes early PAGs, etc.). And the analyzer operates to add four reagents to the reaction vessel to promote the ELISA reaction. The reagents include biotin-labeled anti-pregnancy-associated glycoprotein polyclonal antibody, streptavidin-PolyHRP20, a peroxidase indicator (e.g., a peroxidase substrate, Tetramethylbenzidine, etc.), and hydrochloric acid stop solution. Between reagent additions, the reaction vessel may be washed with a wash buffer including IxPBS with 0.05% Tween20. Upon adding the final reagents, samples that test positive for pregnancy will have a color. For example, samples may have a blue tint, which may further change color after a stop solution is added (e.g., which may change to a yellow color after a stop solution is added, etc.). And samples that are negative for pregnancy may be clear. The color of the samples can be evaluated, for example, by a detection assembly of the analyzer.
[00149] In still another example embodiment, an analyzer may be operable to interface directly with a printer (e.g., without requiring use of a control system as described herein, etc.) to provide test results, for example, in a simple printed format. In this example embodiment, the analyzer may include sufficient memory to store data, for example, for up to five runs of the analyzer.
[00150] In another example embodiment, a method is provided for early detection of pregnancy in an animal (e.g., a bovine animal such as a cow, etc.) using an automated analyzer. The method generally includes collecting a sample from an animal in a sample vessel (e.g., a VACUTAINER tube, etc.), and correlating the sample vessel containing the sample to the animal from which the sample was collected (e.g., via a control system of the analyzer, etc.). The sample vessel containing the sample is then positioned within the analyzer along with a reaction vessel such that the reaction vessel is correlated to the sample vessel. Additional samples may be collected in sample vessels and positioned within the analyzer together with reaction vessels such that each of the reaction vessels are correlated to a given one of the sample vessels. [00151] Once the sample vessel and the reaction vessel are positioned within the analyzer, the method includes transferring at least part of the sample from the sample vessel to the correlated reaction vessel (for each sample vessel and reaction vessel in the analyzer). A robot probe may be used for transferring at least part of the sample from the sample vessel to the reaction vessel with an automated robot probe. An assay is then performed on the sample in the reaction vessel (e.g., a chemical reaction such as an ELISA reaction, etc.) for each reaction vessel containing a sample in the analyzer. Performing the assay may include, for example, incubating the sample in the reaction vessel, washing the robot probe at a cleaning station (e.g., cleaning station 182, etc.), aspirating at least part of the sample from the reaction vessel with the robot probe, again washing the robot probe at the cleaning station, adding a reagent to the reaction vessel with the robot probe, incubating the reagent in the reaction vessel, again washing the robot probe at the cleaning station, and aspirating at least part of the reagent from the sample vessel with the robot probe. This operation can be repeated by the analyzer for any additional reagents required to perform the desired assay. After the assay is complete (e.g., for each sample in the analyzer, etc.), the samples are tested for presence or non-presence of a desired trait (e.g., presence or non-presence of at least one or more PAGs for indicating pregnancy in the animal, etc.). For example, the samples may be optically tested using photometric analysis.
[00152] In other example embodiments, analyzers may include probe assemblies with transfer probes and/or wash probes moveable in at least one or more of a generally horizontal direction (e.g., generally x-direction, a generally y- direction, etc.), a generally rotational direction, a generally vertical direction (e.g., a generally z-direction, etc.), combinations thereof, etc.
[00153] In still other example embodiments, analyzers may include generally stationary carousel assemblies. In these analyzers, probe assemblies and/or detection assemblies of the analyzers may be moveable relative to the carousel assemblies during operation of the analyzers for preparing and/or testing the samples for at least one or more desired traits.
[00154] In other example embodiments, analyzers may include control systems operable to minimize clogging of probes of the analyzers. For example, the analyzers may include software operable to control power failures and/or other inadvertent interruptions of analyzer operations such that runs of the analyzers involving such failures and/or interruptions would not be lost.
[00155] In other example embodiments, analyzers may include detection assemblies configured to perform at least one or more quantitative analysis and/or at least one or more qualitative analysis to determine if given samples contain at least one or more desired traits. For example, in one example embodiment an analyzer may be used to promote chemical reactions involving at least one or more samples in reaction vessels. In this embodiment, the reaction vessels (and samples therein) are manually inspected (visually) for presence of a color to determine if the samples contain a desired trait generally associated with the color.
[00156] In other example embodiments, analyzers may be operable to incubate samples without use of incubation assemblies. For example, in such analyzers incubation of samples may occur as part of the ambient air temperature surrounding the analyzers.
[00157] In still other example embodiments, analyzers may include cartridge inserts containing at least one or more reagents, wash buffers, cleaning/rinsing fluids, etc. to be used with the analyzers. In some embodiments, the cartridge inserts can be replaced for each operational run of the analyzers.
[00158] Example analyzers of the present disclosure may provide on-farm diagnostic blood test results to identify pregnant and/or non-pregnant bovine animals, such as cows, at least ten to twelve days earlier than industry standard tests (e.g., palpation), with about ninety percent accuracy or better. In one example embodiment, an analyzer is operable to provide such tests with about ninety-fiver percent or better accuracy.
[00159] The example analyzers may also be operable to provide on-farm diagnostic blood test results to identify pregnant and/or non-pregnant bovine animals, such as cows, in about four hours or less. In one example embodiment, an analyzer is operable to provide such results in about two hours or less.
[00160] The example analyzers may also be operable to provide on-farm diagnostic blood test results to determine if bovine animals, such as cows, are pregnant or non-pregnant within about thirty days or less following breeding. In one example embodiment, an analyzer is operable to provide such results within about twenty-eight days following breeding. In another example embodiment, an analyzer is operable to provide such results within about twenty-five days following breeding.
[00161] Example analyzers of the present disclosure may include detection assemblies operable to analyze a single reaction vessel during operation to test a sample. By comparison, traditional devices (e.g., spectrophotometers, etc.) often require multiple vessels to complete such testing (e.g., one for calibration, another for sample analysis, etc.).
[00162] Example analyzers of the present disclosure may also provide inexpensive, rugged, portable, automated, etc. analyzers that can be generally easy to operate, use, maintain, etc. The example analyzers may also include features that help reduce the impact of harsh environments (e.g., dust, temperature/humidity swings, flies, insects, etc.) in which the analyzers may be used (e.g., diary farms, etc.). For example, the example analyzers may include primary covers to cover carousel assemblies within housings of the analyzers, along with separate covers (or lids) to cover sample tubes and/or reaction vessels within the housings. Moreover, the analyzers may be configured to generally inhibit air intake from outside analyzers. Thus, generally clean air can be ventilated and moved within incubation assemblies of the analyzers which can be generally enclosed within the analyzers. Such constructions can help reduce migration and/or collection of, for example, dust, etc. within the analyzer and can thus help inhibit contamination of samples.
[00163] Example analyzers of the present disclosure may further provide for flexibility in testing any number of samples, for example, from one sample to hundreds of samples. Time to process runs of the example analyzers can be reduced because sample processing is generally staggered with reagent transfer, incubation, and reaction vessel washing, which can occur substantially simultaneously as carousel assemblies of the example analyzers operate (e.g., rotate, etc.). In addition, probe assemblies of the example analyzers can be configured to wash reaction vessels and transfer fluids substantially simultaneously. For example, wash probes are physically located away from transfer probes such that washing operation can take place substantially simultaneously with fluid transfer operation (e.g., in concert with operation of the carousel assemblies, etc.).
[00164] Example analyzers of the present disclosure may also be generally compact in construction and comprise generally fully contained analysis systems. For example, all samples, reagents, waste collection, etc. are contained within the analyzers. Moreover, automated cleaning cycles may be programmed into control systems of the analyzers to allow for cleaning operations to occur immediately after last samples are read (e.g., optically analyzed, etc.). When complete, users can discard reagent containers, sample vessels, reaction vessels, etc. and the analyzers will be clean and ready for another run.
[00165] Example analyzers of the present disclosure may also include at least one or more outputs, alerts, etc. to inform users if environmental conditions move outside desired operating ranges. In addition, the example analyzers may include at least one or more outputs, alerts, etc. to inform the users that key operations of the analyzers are complete.
[00166] The foregoing description of the embodiments has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention. Individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but, where applicable, are interchangeable and can be used in a selected embodiment, even if not specifically shown or described. The same may also be varied in many ways. Such variations are not to be regarded as a departure from the invention, and all such modifications are intended to be included within the scope of the invention.

Claims

CLAIMSWhat is claimed is:
1. An analyzer for analyzing at least one or more samples for a desired trait, the analyzer comprising: a housing; an incubation assembly located at least partially within the housing; a carousel assembly located at least partially within the incubation assembly and movable relative to the incubation assembly, the carousel assembly configured to support a sample vessel and a reaction vessel; and a probe assembly configured to wash the reaction vessel and transfer a sample contained within the sample vessel to the reaction vessel.
2. The analyzer of claim 1 , further comprising a detection assembly configured to analyze a processed sample in the reaction vessel for a desired trait.
3. The analyzer of claims 1 or 2, further comprising a pump system for moving fluids through the probe assembly.
4. The analyzer of any one of claims 1 , 2, or 3, further comprising a temperature control system for controlling temperature within the incubation assembly.
5. The analyzer of claim 4, wherein the temperature control system includes a feedback control operable to monitor and/or maintain a desired temperature within the incubation assembly.
6. The analyzer of any one of claims 1-5, wherein the incubation assembly includes first and second insulating containers, the first insulating container being disposed at least partially within the second insulating container, and the carousel assembly being disposed at least partially within the first insulating container.
7. The analyzer of claim 6, wherein the incubation assembly includes a heating system for use in warming the reaction vessel, the heating system being disposed generally within the second insulating container.
8. The analyzer of claim 7, wherein the heating system includes a fan for circulating air warmed by the heating system through the first and second insulating containers.
9. The analyzer of claims 7 or 8, wherein the heating system includes a resistive element for warming air within the first and/or second insulating containers.
10. The analyzer of any one of claims 6-8, wherein the first insulating container includes at least one or more inlets for circulating air warmed by the heating system from the second insulating container to the first insulating container, and at least one or more outlets for circulating air from the first insulating container to the second insulating container.
1 1. The analyzer of any one of claims 6-10, further comprising a detection assembly configured to analyze a processed sample in the reaction vessel for a desired trait, wherein at least part of the detection assembly is disposed within the second insulating container.
12. The analyzer of claim 1 1 , wherein at least part of the detection assembly is also disposed within the first insulating container.
13. The analyzer of any one of claim 6, wherein the carousel assembly includes a first carousel configured to support the sample vessel and a second carousel configured to support the reaction vessel.
14. The analyzer of claim 13, wherein the incubation assembly includes a cover configured to be received generally over at least part of the first and second carousels for substantially covering the sample vessel and the reaction vessel.
15. The analyzer of claim 14, wherein the incubation assembly includes a heating system for use in warming the reaction vessel, and wherein the heating system, the first and second insulating containers, and the cover cooperate to help maintain the reaction vessel at a generally constant temperature.
16. The analyzer of any one of claims 1-12, wherein the carousel assembly includes a first carousel configured to support the sample vessel and a second carousel configured to support the reaction vessel.
17. The analyzer of claim 16, wherein the first carousel is received at least partially within the second carousel.
18. The analyzer of claims 16 or 17, wherein the second carousel includes an inner channel, the first carousel being received at least partially within the inner channel of the second carousel.
19. The analyzer of any one of claims 16-18, wherein the first carousel is configured to support one or more sample vessels generally around a perimeter of the first carousel, and wherein the second carousel is configured to support one or more reaction vessels generally around a perimeter of the second carousel.
20. The analyzer of claim 19, wherein each of the one or more sample vessels is generally correlated with a respective one of the one or more reaction vessels, and wherein the probe assembly is configured to transfer a sample contained within each of the one or more sample vessels to the reaction vessel generally correlated therewith.
21. The analyzer of any one of claims 16-20, further comprising means for rotating the first and second carousels relative to the incubation assembly.
22. The analyzer of any one of claims 1-21 , wherein the carousel assembly includes a handle for use in positioning the carousel assembly within the incubation assembly and/or for use in removing the carousel assembly from the incubation assembly.
23. The analyzer of any one of claims 1-22, wherein the probe assembly includes a first probe and a second probe, the first probe configured to generally wash the reaction vessel, and the second probe configured to transfer at least part of the sample contained within the sample vessel to the reaction vessel.
24. The analyzer of claim 23, wherein the first probe is configured to dispense wash fluid into the reaction vessel and aspirate the wash fluid from the reaction vessel to generally wash the reaction vessel.
25. The analyzer of claims 23 or 24, wherein the second probe is further configured to transfer at least part of a reagent contained within a reagent container to the reaction vessel.
26. The analyzer of any one of claims 23-25, wherein the first probe includes a head portion to removably couple the first probe to the probe assembly.
27. The analyzer of any one of claims 23-26, wherein the second probe includes a head portion to removably couple the second probe to the probe assembly.
28. The analyzer of any one of claims 23-27, wherein the first and/or second probes include a stainless steel sleeve and a TEFLON tube extending generally through the sleeve.
29. The analyzer of any one of claims 23-28, wherein the first and/or second probes include a rigid chemical resistant sleeve and non-reactive tube extending generally through the sleeve.
30. The analyzer of any one of claims 23-29, wherein the probe assembly includes a cleaning station configured to wash the second probe.
31. The analyzer of claim 30, wherein the cleaning station includes a first well, a second well, and a gutter generally surrounding the first well, the cleaning station being configured to allow overflow of wash fluid from the first well into the surrounding gutter and then into the second well for removal from the cleaning station.
32. The analyzer of claims 30 or 31 , wherein the cleaning station is configured to wash the second probe before the second probe transfers the sample contained within the sample vessel to the reaction vessel.
33. The analyzer of any one of claims 30-32, wherein the second probe is also operable to transfer at least part of a reagent contained within a reagent container to the reaction vessel, the cleaning station being operable to further wash the second probe before the second probe transfers at least part of the reagent contained within the reagent container to the reaction vessel.
34. The analyzer of any one of claims 23-33, wherein the first and second probes are automated probes operable to move in at least one direction.
35. The analyzer of any one of claims 23-34, wherein the first probe is operable to move in a generally vertical linear direction.
36. The analyzer of any one of claims 23-35, wherein the second probe is operable to move in at least one or more linear direction and at least one or more rotational direction.
37. The analyzer of claim 36, wherein the at least one or more linear directions includes a generally vertical linear direction.
38. The analyzer of any one of claims 23-37, comprising a pump system having at least one or more pumps for moving fluid through the first and/or second probes.
39. The analyzer of claim 1 , further comprising a detection assembly configured to determine an amount of light absorbed and/or emitted by a processed sample in the reaction vessel for use in analyzing said processed sample for the desired trait.
40. The analyzer of claim 39, wherein the detection assembly includes at least one or more detectors configured to measure an amount of light passing through said processed sample for use in determining the amount of light absorbed by said processed sample.
41. The analyzer of claim 40, wherein the at least one or more detectors includes a first detector configured to measure a first amount of light passing through said processed sample at a first wavelength, and a second detector configured to measure a second amount of light passing through said processed sample at a second wavelength.
42. The analyzer of claim 41 , wherein the first wavelength of light is about 620 nanometers and the second wavelength of light is about 450 nanometers.
43. The analyzer of claims 41 or 42, wherein the detection assembly includes a processor configured to determine the amount of light absorbed by the processed sample based on at least the measured first amount of light passing through said processed sample and the measured second amount of light passing through said sample.
44. The analyzer of claim 43, wherein the amount of light absorbed by the processed sample is indicative of presence or non-presence of the desired trait.
45. The analyzer of any one of claims 40-44, wherein the at least one or more detectors includes a light source and a photodetector.
46. The analyzer of claim 45, wherein the light source includes a light emitting diode, and wherein the photodetector includes a phototransistor.
47. The analyzer of claims 45 or 46, wherein the carousel assembly is configured to move the reaction vessel between the light source and the photodetector of the at least one or more detectors during analysis to determine the amount of light absorbed by the processed sample in the reaction vessel, and wherein the light source of the at least one or more detectors passes light through said processed sample and the corresponding photodetector of the at least one or more detectors measures the amount of light at a given wavelength passing through said processed sample from the corresponding light source.
48. The analyzer of any one of claims 45-47, wherein the carousel assembly moves the reaction vessel past the light source and the photodetector of the at least one or more detectors at a generally constant speed during analysis.
49. The analyzer of any one of claims 1-48, further comprising a platform disposed substantially within the housing and configured to support at least part of the carousel assembly and at least part of the probe assembly.
50. The analyzer of claim 49, wherein the platform is further configured to at least partly support at least one or more reagent container, at least one or more pump, and a detection assembly configured to analyze the processed sample in the reaction vessel for a desired trait.
51. The analyzer of claim 49, wherein the carousel assembly is configured to support two or more sample vessels and two or more reaction vessels, and wherein the platform is configured to support at least one or more reagent containers, the probe assembly configured to transfer a sample contained within each of the two or more sample vessels to a correlated one of the two or more reaction vessels and to transfer a reagent contained within the at least one or more reagent containers to each one of the two or more reaction vessels.
52. The analyzer of any one of claims 49-51 , wherein the platform is configured to support at least two or more reagent containers.
53. The analyzer of any one of claims 1 -52, wherein the housing includes a body and a cover, the cover being pivotably coupled to the body to selectively cover and uncover at least part of the incubation assembly, at least part of the carousel assembly, and at least part of the probe assembly.
54. The analyzer of claim 1 , wherein the incubation assembly includes a cover configured to be received generally over at least part of the carousel assembly for substantially covering the sample vessel and the reaction vessel supported by the carousel assembly.
55. The analyzer of claim 54, wherein the probe assembly includes a first probe configured to generally wash the reaction vessel and a second probe configured to transfer the sample contained within the sample vessel to the reaction vessel, and wherein the cover includes an opening for allowing the first probe to access the reaction vessel, an opening for allowing the second probe to access the sample vessel, and an opening for allowing the second probe to access the reaction vessel.
56. The analyzer of any one of claims 1-55, wherein the carousel assembly is configured to support two or more sample vessels and two or more reaction vessels.
57. The analyzer of any one of claims 1 -56, wherein the analyzer is an automated analyzer.
58. The analyzer of any one of claims 1-57, wherein the incubation assembly is automated.
59. The analyzer of any one of claims 1-58, wherein the carousel assembly is automated.
60. The analyzer of any one of claims 1 -59, wherein movement of the probe assembly is automated.
61. The analyzer of any one of claims 2-53 or 56-60, wherein the detection assembly is automated.
62. The analyzer of any one of claims 1-61 , wherein the analyzer is operable to analyze at least one or more liquid samples.
63. The analyzer of claim 62, wherein the analyzer is operable to analyze at least one or more liquid analyte sample.
64. The analyzer of any one of claims 1-63, wherein the analyzer is operable to analyze at least one or more solid samples.
65. The analyzer of any one of claims 1-64, wherein the analyzer is operable to analyze at least one or more whole-blood sample.
66. The analyzer of claim 65, wherein the analyzer is operable to analyze at least one or more whole-blood samples collected from at least one or more animals.
67. The analyzer of claim 65, wherein the analyzer is operable to analyze at least one or more whole-blood samples collected from at least one or more cows.
68. The analyzer of any one of claims 1-67, wherein the analyzer is operable to analyzer at least one or more samples in-field at a farm location.
69. The analyzer of any one of claims 1-68, wherein the analyzer is operable to analyze at least one or more samples for a desired trait including presence of at least one or more pregnancy-associated glycoproteins.
70. The analyzer of claim 69, wherein the analyzer is operable to perform an enzyme-linked immuno-sorbent assay to analyze at least one or more samples for presence of at least one or more pregnancy-associated glycoproteins.
71. The analyzer of any one of claims 1-70, wherein the desired trait includes pregnancy of a bovine animal, the analyzer configured to analyze a biological sample from the bovine animal in about four hours or less to determine if the bovine animal is pregnant or not pregnant.
72. The analyzer of any one of claims 1-71 , wherein the desired trait includes pregnancy of a bovine animal, the analyzer configured to analyze a biological sample from the bovine animal to determine with about ninety percent or better accuracy if the bovine animal is pregnant.
73. The analyzer of any one of claims 1-72, wherein the desired trait includes non-pregnancy of a bovine animal, the analyzer configured to analyze a biological sample from the bovine animal to determine with about ninety percent or better accuracy if the bovine animal is not pregnant.
74. The analyzer of any one of claims 1-73, wherein the desired trait includes pregnancy of a bovine animal, the analyzer configured to analyze a biological sample from the bovine animal to determine if the bovine animal is pregnant or not pregnant within about thirty days or less following breeding.
75. The analyzer of claim 74, wherein the analyzer is configured to determine if the bovine animal is pregnant or not pregnant within about twenty-eight days following breeding.
76. The analyzer of claim 75, wherein the analyzer is configured to determine if the bovine animal is pregnant or not pregnant within about twenty-five days following breeding.
77. An incubation assembly for use with an immunoassay analyzer operable to analyze at least one or more samples for a desired trait, the incubation assembly configured to warm and/or help maintain a generally constant temperature of at least one or more processed samples positioned within the incubation assembly, the incubation assembly comprising: a first insulating container defining a generally open interior region capable of receiving at least one or more samples to be analyzed for a desired trait; a second insulating container defining a generally open interior region, the first insulating container being disposed at least partially within the generally open interior region of the second insulating container; and a heating system disposed generally within the second insulating container and operable to warm and/or help maintain a generally constant temperature of at least one or more processed samples capable of being received into the generally open interior region of the first insulating container.
78. The incubation assembly of claim 77, wherein the incubation assembly includes a cover configured to be received generally over at least part of the generally open interior region of the first insulating container for substantially covering at least one or more samples received within the generally open interior region of the first insulating container.
79. The incubation assembly of claims 77 or 78, wherein the first insulating container includes at least or more one inlets for circulating air warmed by the heating system from the second insulating container to the first insulating container, and at least one or more outlets for circulating air from the first insulating container to the second insulating container.
80. The incubation assembly of claims 78 or 79, wherein the heating system, the first and second insulating containers, and the cover cooperate to help maintain the generally constant temperate of the at least one ore more processed samples received within the generally open interior region of the first insulating container.
81. A carousel assembly for use with an immunoassay analyzer operable to analyze at least one or more samples for a desired trait, the carousel assembly comprising: a first carousel configured to support at least one or more sample vessels generally around a perimeter of the first carousel; and a second carousel configured to support at least one or more reaction vessels generally around a perimeter of the second carousel; wherein the first carousel is received at least partially within the second carousel; and wherein the at least one or more sample vessels and the at least one or more reaction vessels are supported by the first and second carousels such that each sample vessel is correlated to a respective one of the at least one or more reaction vessels, and each sample vessel is positioned radially adjacent its correlated reaction vessel; whereby each of the one or more reaction vessels is configured to receive a sample from a correlated one of the at least one or more sample vessels for analysis for a desired trait, and whereby each of the at least one or more reaction vessels can be readily matched with the sample vessel from which the respective sample was received.
82. The carousel assembly of claim 81 , wherein the second carousel includes an inner channel, the first carousel being received at least partially within the inner channel of the second carousel.
83. The carousel assembly of claims 81 or 82, wherein the carousel assembly includes means for rotating the first and second carousels.
84. The carousel assembly of any one of claims 81-83, wherein the carousel assembly includes a handle for use in grasping the carousel assembly and/or moving the carousel assembly.
85. A probe assembly for use with an immunoassay analyzer operable to analyze at least one or more samples for a desired trait, the immunoassay analyzer supporting at least one or more sample vessels and at least one or more reaction vessels with each of the at least one or more reaction vessels being correlated to each of the at least one or more sample vessels, the probe assembly operable to wash each of the at least one or more reaction vessels and transfer a sample contained within each of at least one or more sample vessels to a correlated one of the at least one or more reaction vessels, the probe assembly comprising: a support platform configured to be coupled to a work surface of an immunoassay analyzer; a first probe supported by the support platform and configured to generally wash each of at least one or more reaction vessels; a second probe supported by the support platform adjacent the first probe and configured to transfer at least part of a sample contained within each of at least one or more sample vessels to a correlated one of at least one or more reaction vessels; and a cleaning station configured to wash the first and/or second probes.
86. The probe assembly of claim 85, wherein the first probe is configured to dispense wash fluid into each of the one ore more reaction vessels and aspirate the wash fluid from the reaction vessel to generally wash the reaction vessel.
87. The probe assembly of claims 85 or 86, wherein the second probe is further configured to transfer at least part of a reagent contained within a reagent container to each of the at least one or more reaction vessels.
88. The probe assembly of claim 87, wherein the cleaning station is configured to wash the second probe before the second probe transfers the sample contained within each of the at least one or more sample vessels to the correlated one of the at least one or more reaction vessels and before the second probe transfers the reagent contained within the reagent container to each of the at least one or more reaction vessels.
89. The probe assembly of any one of claims 85-88, wherein the cleaning station includes a first well, a second well, and a gutter generally surrounding the first well, the cleaning station being configured to allow overflow of wash fluid from the first well into the surrounding gutter and then into the second well for removal from the cleaning station
90. The analyzer of any one of claims 85-89, wherein the first probe is operable to move in a generally vertical linear direction.
91. The analyzer of any one of claims 85-90, wherein the second probe is operable to move in at least one or more linear direction and at least one or more rotational direction.
92. The probe assembly of any one of claims 85-91 , wherein the first probe includes a head portion to removably couple the first probe to the probe assembly.
93. The analyzer of any one of claims 85-92, wherein the second probe includes a head portion to removably couple the second probe to the probe assembly.
94. The probe assembly of any one of claims 85-93, wherein the first probe includes a dispensing member operable to transfer wash fluid to at least one or more reaction vessels, and an aspirating member operable to remove the wash fluid from the at least one or more reaction vessels.
95. A detection assembly for use with an immunoassay analyzer operable to analyze at least one or more samples for a desired trait, the detection assembly operable to determine an amount of light emitted by at least one or more processed samples for use in indicating presence and/or non-presence of the desired trait in each of the at least one or more processed samples, the detection assembly comprising: a first detector having a light source and a photodetector, the first detector configured to measure a first amount of light at a first wavelength passing through each of at least one or more processed samples to be analyzed for a desired trait by an immunoassay analyzer; and a second detector having a light source and a photodetector, the second detector configured to measure a second amount of light at a second wavelength passing through each of the at least one or more processed samples to be analyzed for the desired trait by the immunoassay analyzer; wherein each of the at least one or more processed samples is moved at a generally constant speed past the light source and the photodetector of the first detector and past the light source and the photodetector of the second detector; and wherein the light source of the first detector emits light passing through each of the at least one or more processed samples and the photodetector of the first detector measures the amount of light at the first wavelength passing through each of the at least one or more processed samples, and the light source of the second detector emits light passing through each of the at least one or more processed samples and the photodetector of the second detector measures the amount of light at the second wavelength passing through each of the at least one or more processed samples.
96. The detection assembly of claim 95, wherein the first wavelength of light is about 620 nanometers and the second wavelength of light is about 450 nanometers.
97. The detection assembly of claims 95 or 96, further comprising a processor configured to determine the amount of light absorbed by each of the at least one or more processed samples based on at least the measured first amount of light passing through each of the at least one or more processed samples at the first wavelength and the measured second amount of light passing through each of the at least one or more processed samples at the second wavelength.
98. The detection assembly of claim 97, wherein the amount of light absorbed by each of the one or more processed samples is indicative of the presence and/or non-presence of the desired trait.
99. The detection assembly of any one of claims 95-98, wherein the light sources each include a light emitting diode, and wherein the photodetectors each include a phototransistor.
100. A kit for use with an immunoassay analyzer operable to analyze at least one or more samples for a desired trait, the kit comprising: at least one or more sample vessels configured to receive a sample to be analyzed by an immunoassay analyzer for a desired trait; at least one or more reaction vessels capable of being correlated to the at least one or more sample vessels and configured to receive at least part of the sample from the at least one or more sample vessels for analysis by the immunoassay analyzer for the desired trait, the at least one or more reaction vessels being generally coated with an antibody; at least one or more reagents each configured to be added to the at least one or more reaction vessels for reacting with said at least part of the sample received therein for use in preparing said sample for analysis by the immunoassay analyzer for the desired trait; and a wash buffer for use in washing the at least one or more reaction vessels before the at least one or more reaction vessels receive a reagent.
101 . The kit of claim 100, wherein the at least one or more reaction vessels are generally coated with a monoclonal antibody.
102. The kit of claims 100 or 101 , further comprising: a control sample that tests positive for the desire trait by the immunoassay analyzer; and a control sample that tests negative for the desired trait by the immunoassay analyzer.
103. The kit of any one of claims 100-102, wherein the wash buffer includes IxPBS with 0.05% Tween20.
104. The kit of any one of claims 100-103, comprising first, second, and third reagents, the first reagent including biotin-labeled anti-pregnancy-associated glycoprotein polyclonal antibody, the second reagent including streptavidin- PolyHRP20, and the third reagent including a peroxidase indicator.
105. The kit of claim 104, further comprising a fourth reagent, the fourth reagent including a stop solution.
106. The kit of claim 105, wherein the stop solution includes an acid.
107. The kit of any one of claims 100-106, comprising at least thirty or more sample vessels and/or at least thirty or more reaction vessels.
108. The kit of any one of claims 100-106, comprising thirty or less sample vessels and/or thirty or less reaction vessels.
109. The kit of any one of claims 100-108, wherein the kit is for use with an immunoassay analyzer operable to analyze one more blood samples collected from at least one or more animals for a desired trait including presence or non-presence of at least one or more pregnancy-associated glycoproteins.
1 10. The kit of claim 109, wherein the kit is for use with an immunoassay analyzer operable to analyze at least one or more blood samples collected from at least one or more cows.
1 1 1 . The kit of any one of claims 100-1 10, wherein the kit is for use with an immunoassay analyzer operable to perform an enzyme-linked immuno-sorbent assay to analyze the at least one or more samples for presence or non-presence of at least one or more pregnancy-associated glycoproteins.
1 12. The kit of any one of claims 100-1 1 1 , further comprising a cleaning solution and a rinsing solution for use in cleaning the fluidics assembly of the immunoassay analyzer.
1 13. A method for early detection of pregnancy in an animal using an automated analyzer, the method comprising: collecting a sample from an animal in a sample vessel; correlating the sample vessel containing the sample to the animal from which the sample was collected; positioning the sample vessel in an automated analyzer; positioning a reaction vessel in the automated analyzer in a position such that the reaction vessel can be correlated to the sample vessel; transferring at least part of the sample from the sample vessel to the reaction vessel; processing the sample by performing an enzyme-linked immuno-sorbent assay on the sample in the reaction vessel; and analyzing the processed sample after performing the enzyme-linked immuno- sorbent assay for presence or non-presence of at least one or more pregnancy- associated glycoproteins for indicating pregnancy in the animal.
1 14. The method of claim 1 13, wherein transferring at least part of the sample from the sample vessel to the reaction vessel includes transferring at least part of the sample from the sample vessel to the reaction vessel with an automated robot probe.
1 15. The method of claim 1 14, wherein performing an enzyme-linked immuno-sorbent assay on the sample in the reaction vessel includes: incubating the reaction vessel after transferring at least part of the sample thereto; washing the robot probe at a cleaning station; aspirating fluid from the reaction vessel with the robot probe; washing the robot probe at the cleaning station; adding a reagent to the reaction vessel with the robot probe; incubating the reaction vessel after adding the reagent thereto; washing the robot probe at the cleaning station; and aspirating fluid from the reaction vessel again with the robot probe.
1 16. The method of claim 1 15, wherein performing an enzyme-linked immuno-sorbent assay on the sample in the reaction vessel further includes repeating the processes of adding a reagent to the reaction vessel with the robot probe, incubating the reaction vessel, washing the robot probe at the cleaning station, and aspirating fluid from the reaction vessel with the robot probe for at least two or more additional reagents.
1 17. The method of any one of claims 1 13-1 16, wherein analyzing the processed sample after performing the enzyme-linked immuno-sorbent assay for presence of at least one or more pregnancy-associated glycoproteins includes performing an optical analysis on the processed sample.
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US20140025199A1 (en) * 2012-07-23 2014-01-23 Pharmadva, LLC Object dispenser having a variable orifice and image identification
EP2690445A1 (en) * 2011-03-25 2014-01-29 Shenzhen Mindray Bio-Medical Electronics Co., Ltd. Apparatus for automatic analysis and sample analysis method thereof
CN104483499A (en) * 2014-12-30 2015-04-01 深圳市汇松科技发展有限公司 Full-automatic particular protein analyzer
CN104865397A (en) * 2015-05-23 2015-08-26 深圳德夏生物医学工程有限公司 Portable multi-channel biochemical and specific protein analyzer
WO2018169651A1 (en) * 2017-03-16 2018-09-20 Siemens Healthcare Diagnostics Inc. System and method for thermal control of incubation system in diagnostic analyzer
CN109030809A (en) * 2018-10-31 2018-12-18 蓝怡科技集团股份有限公司 A kind of anaphylactogen IgE antibody automatic analyzer
KR20190001156A (en) * 2017-06-26 2019-01-04 (주)아이엠 Quantitative analysis diagnose apparatus
US10360751B2 (en) 2012-07-23 2019-07-23 Pharmadva, LLC Object dispenser having a variable orifice and image identification
CN111788488A (en) * 2017-12-29 2020-10-16 拜克门寇尔特公司 Probe wash arrangement with multiple configurations for sample analyzer and method of use thereof
CN112230008A (en) * 2020-12-18 2021-01-15 南京澳林生物科技有限公司 Portable POCT full-automatic biochemical analyzer and use method thereof
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EP2690445A1 (en) * 2011-03-25 2014-01-29 Shenzhen Mindray Bio-Medical Electronics Co., Ltd. Apparatus for automatic analysis and sample analysis method thereof
EP2690445A4 (en) * 2011-03-25 2014-10-08 Shenzhen Mindray Bio Med Elect Apparatus for automatic analysis and sample analysis method thereof
CN103596688B (en) * 2012-05-30 2016-02-24 埃佩多夫股份公司 The application of the device for positioning vessel and the device for positioning vessel
US10267815B2 (en) 2012-05-30 2019-04-23 Eppendorf Ag Device for positioning vessels and utilization of a device for positioning vessels
CN103596688A (en) * 2012-05-30 2014-02-19 埃佩多夫股份公司 Device for positioning vessels, and the use of same
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WO2013178235A1 (en) * 2012-05-30 2013-12-05 Eppendorf Ag Device for positioning vessels, and the use of same
US9501887B2 (en) * 2012-07-23 2016-11-22 Pharmadva, LLC Object dispenser having a variable orifice and image identification
US10360751B2 (en) 2012-07-23 2019-07-23 Pharmadva, LLC Object dispenser having a variable orifice and image identification
US20140025199A1 (en) * 2012-07-23 2014-01-23 Pharmadva, LLC Object dispenser having a variable orifice and image identification
US11610657B2 (en) 2013-12-18 2023-03-21 Stuart Renwick Locklear Automated pill dispenser
US10984901B1 (en) 2013-12-18 2021-04-20 Stuart Renwick Locklear Method and system to implement medical information tracking system and medication dispenser
CN104483499A (en) * 2014-12-30 2015-04-01 深圳市汇松科技发展有限公司 Full-automatic particular protein analyzer
CN104865397A (en) * 2015-05-23 2015-08-26 深圳德夏生物医学工程有限公司 Portable multi-channel biochemical and specific protein analyzer
WO2018169651A1 (en) * 2017-03-16 2018-09-20 Siemens Healthcare Diagnostics Inc. System and method for thermal control of incubation system in diagnostic analyzer
KR102000661B1 (en) * 2017-06-26 2019-10-01 (주)아이엠 Quantitative analysis diagnose apparatus
KR20190001156A (en) * 2017-06-26 2019-01-04 (주)아이엠 Quantitative analysis diagnose apparatus
CN111788488A (en) * 2017-12-29 2020-10-16 拜克门寇尔特公司 Probe wash arrangement with multiple configurations for sample analyzer and method of use thereof
CN109030809A (en) * 2018-10-31 2018-12-18 蓝怡科技集团股份有限公司 A kind of anaphylactogen IgE antibody automatic analyzer
CN112230008A (en) * 2020-12-18 2021-01-15 南京澳林生物科技有限公司 Portable POCT full-automatic biochemical analyzer and use method thereof
CN117686670A (en) * 2024-02-02 2024-03-12 内蒙古蒙牛乳业(集团)股份有限公司 Sample automatic detection system and intelligent laboratory
CN117686670B (en) * 2024-02-02 2024-05-03 内蒙古蒙牛乳业(集团)股份有限公司 Sample automatic detection system and intelligent laboratory

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