Automated immunoassay analyzer

• US 5,885,530 A
• Filed: 07/10/1998
• Issued: 03/23/1999
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: DPC Cirrus, Inc.
• Inventors: Palmieri, Thomas, Babson, Arthur L., Fleischer, Eric C., Montalbano, Greg A., Montalbano, Chris P., Montalbano, Anthony P.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US09/113,513
• Time in Patent Office: 256 Days
• Field of Search: 422/63-67, 422/68.1, 422/81, 422/100, 422/101, 422/102, 422/104, 636/43, 636/47-49, 636/174, 636/172, 636/180, 636/179
• US Class Current: 422/65
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: G01N 2035/00435 Refrigerated reagent storage
• CPC Class Codes: G01N 2035/0405 manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: G01N 2035/0451 composed of interchangeable sectors
• CPC Class Codes: G01N 35/02 using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations G01N35/0098 and G01N35/0099 take precedence
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/115831 Condition or time responsive
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An improved automated immunoassay analyzer including a high throughput automated immunoassay system which can perform high volume testing on a broad range of analytes while selecting from among a diverse set of immunoassays for any given sample. The immunoanalyzer has the capacity to perform a wide range of different types of immunoassays by facile storage and automated combination aboard the instrument among a wide variety of different types of reagents and heterogenous immunoassay beads stored on-board the instrument. The automated design allows reduced user interface (e.g., tests are performed automatically from computer input) including the ability to order, perform and reassay tests reflexively based on test results without operator intervention. Further, the inventive analyzer is not sample tube specific; that is, an instrument that can accept sample tube sizes within a broad size range. The inventive automated immunoassay analyzer also provides a re-useable sample dilution well, and a high speed bead washing station that eliminates the need for assay tubes having integral, waste fluid collection chambers.

Claims

1. An automated immunoassay analyzer, comprising;

an instrument which includes

(i) means for receiving a plurality of sample tubes containing a fluid sample to be assayed, wherein said sample tube receiving means comprises at least one sample tube rack supported on a rotatable sample tube carousel;

(ii) means for supplying a plurality of reaction tubes in which an assay on said samples can be performed;

(iii) inert support supply and dispensing means for receiving a plurality of inert support dispensing packs each storing a single type of biomaterial-coated inert support, said biomaterial capable of selectively binding an analyte of interest in a sample, and said dispensing packs capable of storing and dispensing said supports, individually, into a reaction tube at a support dispensing station, whereby a plurality of different biomaterial coated supports stored on-board said analyzer can be selected from for addition to said reaction tube for performing a particular assay in said reaction tube, and said inert support supply and dispensing means comprises a rotatable inert support pack carousel;

(iv) means for receiving a plurality of reagent storage packs capable of storing and permitting reagent withdrawal, in a self-sealing manner, whereby a plurality of different reagents stored on-board said analyzer can be selected from for addition to said reaction tube for performing a particular assay in said reaction tube, wherein said means for receiving a plurality of reagent storage packs comprises a rotatable reagent pack carousel;

(v) means for pipetting sample and means for pipetting reagent into a support containing reaction tube at a reaction tube pipetting station;

(vi) an incubating station for incubating reaction tubes received from said reaction tube pipetting station containing sample, reagent and inert support;

(vii) a washing station for washing bound biomaterial in said reaction tubes after said reaction tubes have been incubated at said incubating station;

(viii) a detection station for detecting a quantity of analyte bound to said biomaterial in said reaction tubes after said reaction tubes have been washed at said washing station, said detection station producing a signal proportional to the quantity of analyte for each reaction tube;

(ix) a reaction rube transport pathway connecting, in this sequence, said reaction tube supply means, said inert support supply and dispensing means, said reaction tube pipetting station, said incubating station, said washing station and said detection station;

(x) means for identifying said sample tubes and said reagent packs on-board the analyzer;

(xi) means for identifying said inert support dispensing packs said means for identifying said inert support dispensing packs coordinating with said means for identifying said simple tubes and said reagent packs such that each sample of said plurality of samples and appropriate types of reagent and biomaterial-coated inert support for said each sample of said plurality of samples are provided to said reaction tubes;

(xii) control means for automatic controlling of various components of said analyzer in a coordinated manner and being capable of executing assay selection orders for each sample of said plurality of samples by selecting and coordinating the introduction of a particular type of reagent and particular type of biomaterial-coated inert support effective to perform a particular requested assay on said each sample in a reaction tube, wherein said control means further coordinates said appropriate types of reagent and said appropriate types of biomaterial-coated inert support effective to perform other particular requested assays on further samples of said plurality of samples in said reaction tube, and whereby said sample tube carousel said reagent pack carousel and said inert support pack carousel are independently rotatable relative to each other; and

(xiii) means for determining, and displaying and/or recording the concentration of the analyte in a particular sample based on said signal produced and detected at said detection station.

2. The automated immunoassay analyzer of claim 1, wherein each of said rotatable sample tube carousel, said rotatable reagent pack carousel, and said rotatable inert support pack carousel, are associated with a bar code reader, whereby said control means can controllably track and advance said sample tubes to said sample pipetting means, said reagent packs to said reagent pipetting means, and said inert support dispensing packs to said inert support dispensing station.

3. The automated immunoassay analyzer of claim 1, wherein said control means includes a computer connected to said analyzer via data communication lines.

4. The automated immunoassay analyzer of claim 3, wherein said computer is connected via data communication lines to (a) a display means which visually displays operator commands and data collected from the instrument, and (b) a keyboard allowing input of patient information associated with test samples.

5. The automated immunoassay analyzer of claim 3, wherein said analyzer includes microprocessing means on-board the analyzer directing operation of said analyzer.

6. The automated immunoassay analyzer of claim 1, wherein said detection station includes a means for detecting light.

7. The automated immunoassay analyzer of claim 6, wherein said means for detecting light is a photomultiplier tube.

8. The automated immunoassay analyzer of claim 1, wherein said sample container rack comprises:

a base;

a sample container holder slave, including;

a cylindrical-shaped shell defining a sidewall structure, an upper opening, and an interior space, and said shell being oriented vertically relative to said base and including a vertically extending slot opening in said sidewall structure, and

a plurality of sample container gripping means attached to said sidewall structure each having at least one projection tab resiliently urged inward, said projection tabs capable of gripping a sidewall of a sample container inserted into said shell to maintain said sample container in a centered, upright orientation.

9. The automated immunoassay analyzer of claim 1, wherein said inert support supply and dispensing means comprises:

(1) a plurality of bead dispenser devices supported on a common bead dispenser device carousel capable of rotation, wherein each dispenser device comprises

(a) a track capable of storing and feeding a plurality of substantially spherical beads by effect of gravity to a lower track end,

(b) an enclosure sealingly housing said track, comprising;

a side wall enclosing outer lateral surfaces of said track,

a cover sealingly enclosing an upper track end of said track and upper end of said side wall, and

a base including upper and lower sections defining a plunger chamber, and a first bead chamber defined in said upper section communicating with said lower track end and said first bead chamber being offset along said plunger chamber relative to a bead exit opening in said lower section,

(c) a plunger sealingly provided in said plunger chamber and being capable of horizontal reciprocal movement within said plunger chamber, said plunger having a throughhole defining a second bead chamber normally aligned with said first bead chamber at said lower track end and with a plunger portion concurrently blocking said exit opening via a biasing means imposing a normal horizontal bias force on said plunger, wherein when a horizontal force is exerted in opposition to and adequate to overcome said normal bias force said plunger being capable of horizontal movement to align said second bead chamber with said exit opening, said normal horizontal biasing force of said biasing means capable of horizontally moving said plunger effective to reblock said exit opening upon removal of said opposing force; and

(2) identifying means for identifying each of said bead dispenser devices.

10. The automated immunoassay analyzer of claim 1, wherein said means for storing reagent packs comprises:

a plurality of reagent containers removably fitted onto a common reagent carousel, each said reagent container comprising;

a vessel having a plurality of separate compartments defined by sidewalls and a cover as an upper surface, each compartment having an opening in said upper surface;

a self-sealing lid attached to the exterior of a sidewall of said vessel, comprising;

a first arm confronting said upper surface of said vessel, said first arm supporting a plurality of caps interspaced by openings extending through said arm, said first arm capable of reciprocal movement over said upper surface of said vessel to permit covering and uncovering of said compartment openings by said caps,

a second arm confronting said exterior sidewall of said vessel, said second arm having a lower end attached to said sidewall of said vessel and an upper end connected to said first arm via a first hinge,

guide means maintaining reciprocal displacement of said first arm along a single horizontal line of movement, and

whereby said first arm of said lid is subject to a normal bias force created by said second arm whereby said plurality of caps normally covers said compartment openings, wherein when a horizontal external force is exerted in opposition to and adequate to exceed said normal bias force said first arm being capable of horizontal displacement adequate to uncover said caps from said compartment openings, and upon removal of said horizontal external force said normal bias force acting on said first arm of said lid to re-cover said compartment openings with said caps.

11. The automated immunoassay analyzer of claim 1, wherein said washing station comprises:

a tube spinning station having

a rotatable chuck, wherein said chuck comprises a body portion and a plurality of spaced apart teeth defining intervening grooves extending through said body portion with at least one of said grooves permitting passage of fluid through said body portion and at least one other of said grooves providing means to receive and mechanically connect a projection on an open end of a tube,

a fluid waste chamber housing said chuck, and said waste chamber comprises means to collect and drain fluid, and an aperture defined in a lower side of said chamber having a size effective to permit entry of a tube into said chamber,

a pipette for dispensing wash water into a tube, said pipette located centrally within said chuck, and

drive means to rotate said chuck.

12. The automated immunoassay analyzer of claim 1, wherein said means for receiving a plurality of sample tubes containing a fluid sample to be assayed further receives tubes containing diluent material, and said analyzer further comprising a sample dilution station, comprising:

(a) a dilution tube well capable of receiving sample and diluent via said sample pipetting means, and (b) means on-board the analyzer to rotate said dilution tube well sufficient to form a homogenous mixture, wherein said sample pipetting means being capable of transferring portions of said mixture to reaction pipetting station, and said dilution well rotation means capable of high speed rotation of said dilution tube well to eliminate excess mixture fluid, and (c) means on-board the analyzer for catching said mixture fluid expelled during said high speed rotation.

13. The automated immunoassay analyzer of claim 12, wherein said sample dilution system further comprises, in combination:

a dilution well waste chamber defined by (a) a chamber body having inner sidewalls and a bottom defining a space, wherein said bottom includes a drainage port and a centrally located opening, and (b) a dilution well-cover having a central hole, said dilution well cover being removably fitted upon said dilution well body to cover said space;

a dilution well, including;

an elongated hollow cylinder having inside walls, an upper end and an lower end, said upper end having an opening and said lower end having a plurality of inward projecting fins integral with said inside tube walls;

a dilution well spinning means, including;

a holding means for conformably receiving and supporting said dilution well,

a drive means capable of effecting rotation of said holder and said dilution well.

15. The automated immunoassay analyzer of claim 1, wherein said pipetting sample means and said pipetting reagent means are located within a central portion of said means for receiving a plurality of sample tubes, said pipetting sample means travels in an arcuate path between (i) a probe washing station in the central portion, (ii) a sample pipetting station on said means for receiving a plurality of sample tubes, (iii) a dilution well and (iv) said pipetting station, and said pipetting reagent means travels in an arcuate path between (i) said rotatable reagent pack carousel and (ii) said pipetting station.

16. The automated immunoassay analyzer of claim 1, wherein said pipetting sample means and said pipetting reagent means are located within a central portion of said means for receiving a plurality of sample tubes, said pipetting sample means and said pipetting reagent means travel in an arcuate path each having a radius from a single point proximate to said pipetting station.

14. An automated immunoassay analyzer, comprising:

sample tube receiving member which receives a plurality of sample tubes filled with fluid samples to be analyzed;

reaction tube receiving member which includes a plurality of reaction tubes in which immunoassay assay reactions are conducted;

sample transfer station for transferring at least a portion of said fluid sample from one of said sample tubes into one of said reaction tubes;

a plurality of inert supports, each having associated therewith one of a plurality of different biomaterial specific for binding one of a plurality of different analytes;

a first scanner identifying said plurality of different biomaterial;

dispenser for dispensing a selected on of said plurality of inert supports into said one of said reaction tubes;

a plurality of reagents used in a plurality of different immunoassays;

a second scanner for identifying each fluid sample of said plurality of fluid samples and said plurality of reagents said second scanner coordinating with said first scanner such that each fluid sample of said plurality of fluid samples and appropriate types of reagent and biomaterial for said each sample of said plurality of samples are provided to said reaction tubes;

reagent transfer station for transferring at least one of said reagents into said one of said reaction tubes based on a selected one of said plurality of inert supports dispensed into said reaction tube by said dispenser;

incubation station for incubating a sample, an inert support and a reagent in said one of said reaction tubes;

washing station for washing said inert support;

detection station for detecting analyte bound to said inert support;

indicator for indicating a concentration of analyte detected at said detection station;

sample tube identifier for identifying each of a plurality of sample tubes;

inert support identifier for identifying each of a plurality of inert supports;

reagent identifier for identifying each of a plurality of reagents; and

computer controller which interfaces with said sample tube identifier, said inert support identifier, said reagent identifier, said dispenser, said first and second scanners, and said reagent transfer station, said computer controller being programmable to permit said analyzer to perform one or a plurality of different immunoassays on each of a plurality of samples in said plurality of sample tubes, said computer controller controlling which of a plurality of immunoassays are conducted on a sample of said plurality of samples in said one of said reaction tubes by selecting said inert support dispensed by said dispenser and said reagent transferred at said reagent transfer station, wherein said computer controller further coordinates other types of reagent and other types of biomaterial effective to perform other particular requested assays on further samples of said plurality of samples in said reaction tubes.