Incubation chamber

• US 5,599,501 A
• Filed: 11/10/1994
• Issued: 02/04/1997
• Est. Priority Date: 11/10/1994
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: CIBA Vision Corporation (Novartis Ag)
• Inventors: Malek, Michael L., Carey, Glen A.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/338,022
• Time in Patent Office: 817 Days
• Field of Search: 422/63, 422/64, 422/67, 422/100, 422/104, 422/52, 436/43, 436/45, 436/47, 436/48, 436/49, 436/54, 436/174, 436/175, 436/179, 436/180, 436/164, 436/165, 436/172, 436/50
• US Class Current: 422/64
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: G01N 2035/0455 Coaxial carousels
• CPC Class Codes: G01N 35/0092 Scheduling
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/025 having a carousel or turntable for reaction cells or cuvettes
• 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 436/114998 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 436/119163 with aspirator of claimed structure
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25125 Digestion or removing interfering materials
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Method and apparatus for transportation and processing of multiple protocol assays within an automated immunoassay analyzer instrument. The apparatus includes a cuvette ring movably coupled to a magnet ring. In one embodiment, the magnet ring and cuvette ring are provided having circular shapes. A temperature controlled housing is disposed about the cuvette and magnet rings to provide a rotary incubation and particle separation chamber. The cuvette ring holds a plurality of cuvettes each of which may have a different assay disposed therein. The cuvette ring advances the cuvettes around the circumference of the incubation chamber. A plurality of discrete processing centers for aspiration and dispensing fluid samples, reagents and wash fluids are disposed at predetermined positions about the incubation chamber. The cuvette ring moves cuvettes in both clockwise and counter clockwise directions around the incubation chamber to position particular cuvettes at particular ones of the plurality of discrete processing centers to thus accommodate different protocols of each of the assays. By controlling the manner in which the cuvette ring moves within the incubation chamber, a plurality of different protocol assays each of which require different incubation times, can be simultaneously processed in the analyzer instrument.

Claims

1. An incubation assembly for handling biological samples and test reagents in an automated biological testing system, said assembly comprising:

at least first and second rings, relatively rotatable in response to control signals, at least one of which rings is adapted for holding sample cuvettes in spaced cuvette receiving positions and at least one other of said rings has one or more magnets that selectively applies a magnetic force to a combination of a biological sample and a test reagent present in one of said cuvettes by relative rotation of the first and second rings in response to said control signals to place said one or more magnets adjacent to said cuvette holding said combination;

an indexing mechanism having a trigger and that positions the first and second rings relative to each other at any one of a plurality of positions corresponding to the number of cuvette receiving positions;

an escapement operatively connected to said indexing mechanism for selectively coupling and enabling relative motion between the first and second rings by at least a distance between adjacent cuvette receiving positions in response to rotation of said first and second rings past said trigger;

at least one sample dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of said biological sample to be tested from a sample supply to said sample cuvette in one said ring at at least one first position to which cuvettes in that ring can be rotated;

at least one test reagent dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of said test reagent from a reagent supply to said biological sample in said sample cuvette to form said sample and reagent combination in said sample cuvette in one said ring adapted for holding cuvettes at at least one second position to which cuvettes in that ring can be rotated;

a cuvette placement assembly having a supply of cuvettes and a cuvette delivery mechanism delivering cuvettes to at least one third position to which a cuvette receiving position in said at least one ring adapted for holding cuvettes can be placed by rotation of said cuvette holding ring in response to said control signals;

a cuvette extraction assembly that extracts said sample and reagent combination containing cuvettes from at least one fourth position to which a cuvette in said at least one ring adapted for holding sample cuvettes can be placed by rotation of said cuvette holding ring in response to said control signals;

a luminometer for receiving an extracted cuvette and having a doser and photosensor to create and detect luminescence in the cuvette representative of properties of each sample under test;

a scheduler of said control signals providing coordinated rotation of said at least first and second rings, sample and reagent dosing assemblies and cuvette placement and extraction assemblies for incubation of said sample and reagent combination in each cuvette for selectable incubation times and positioning of said one or more magnets in said ring that selectively applies a magnetic force adjacent to each said cuvette containing said sample and reagent combination prior to said cuvette extraction by said cuvette extraction assembly.

2. The incubation assembly of claim 1 wherein said magnet is operative to attract paramagnetic particles in the sample and reagent containing cuvettes when the second ring is so placed as to have the magnet adjacent selected cuvettes.

3. The incubation assembly of claim 2 wherein said scheduler includes scheduling to place the magnet adjacent to a cuvette after a predetermined incubation time variable over a range of sample and reagent combinations.

4. The incubation assembly of claim 3 wherein:

said magnet is split forming at least two magnet segments;

at least one wash assembly is provided having one or more probes for withdrawing and supplying fluid at cuvettes in said first ring when positioned adjacent one of said magnet segments in response to said control signals to effect removal of undesired artifacts in the cuvettes before extraction.

5. The incubation assembly of claim 4 wherein said scheduler coordinates the wash assembly and relative rotation of said first and second rings to provide paramagnetic particle on a cuvette side, removal of the remainder of residual cuvette fluid, injection of a neutral fluid medium, resuspension of the paramagnetic particles.

6. The incubation assembly of claim 5 wherein said scheduler provides coordinated placement of said first and second rings and control of said wash assembly for repetition of the fluid removal, injection and resuspension.

7. The incubation assembly of claim 5 wherein said scheduler provides for rotation of said first and second rings in both clockwise and counterclockwise directions.

8. The incubation assembly of claim 1 wherein said scheduler rotates the escapement to the indexing trigger on a periodic schedule.

9. The incubation assembly of claim 1 wherein said luminometer includes a cuvette contents remover and cuvette ejector for removing separately cuvette contents and cuvette to waste sites after detection of luminescence in each cuvette.

10. The incubation chamber of claim 1 wherein said scheduler includes data indicating a plurality of test protocols for testing sample types with selected reagents for selected sample properties.

11. The incubation assembly of claim 10 wherein the scheduler data further includes an identifier of each sample awaiting test and the associated test protocol to be run for each sample awaiting test.

12. The incubation assembly of claim 11 wherein said scheduler further includes instructions for selecting each sample and placing said sample in an empty cuvette in said ring adapted for holding sample cuvettes where said sample can be tested according to a protocol associated with said sample.

13. The incubation assembly of claim 12 wherein said scheduler selects the sample on a predetermined prioritization basis.

14. The incubation assembly of claim 13 wherein said predetermined prioritization basis is selected from the group consisting of FIFO and maximization of a number of tests per unit time.

15. The incubation assembly of claim 1 wherein said scheduler provides the control signals within one of a plurality of different repeating time frames each of substantially similar duration.

16. The incubation assembly of claim 15 wherein each time frame is divided into periods of rotation of the rings and of alternate control signal generation including control signals for activation of the sample dosing assembly, reagent dosing assembly, cuvette placement assembly, and cuvette extraction assembly.

17. The extraction assembly of claim 16 wherein said time frame has four subframes each of which has at least one alternate control signal generation.

18. The incubation assembly of claim 4 wherein said scheduler provides the control signals within one of a plurality of different repeating time frames each of substantially similar duration.

19. The incubation assembly of claim 18 wherein each time frame is divided into periods of rotation of the rings and of alternate control signal generation including control signals for activation of the sample dosing assembly, reagent dosing assembly, cuvette placement assembly, wash assembly and cuvette extraction assembly.

20. The extraction assembly of claim 19 wherein said time frame has four subframes each of which has at least one alternate control signal generation.

21. The incubation assembly of claim 1 further including a bearing structure supporting said first and second rings for relative rotation.

22. The incubation assembly of claim 1 wherein said trigger is a mechanical arm positioned to engage said escapement upon rotation of said escapement with the first and second rings past said arm.

23. An incubation assembly for handling biological samples and test reagents in an automated biological testing system, said assembly comprising:

at least first and second rings, selectively associated for both fixed and independent rotation in response to control signals, at least one of which rings is adapted for holding sample cuvettes in spaced cuvette receiving positions and at least one other of said rings has a sample and reagent condition effector that is selectively applied to a biological sample and test reagent combination in said cuvettes by relative rotation of the first and second rings in response to said control signals;

a bearing structure supporting said first and second rings for relative rotation;

at least one sample dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of a sample to be tested from a sample supply to a cuvette in one said ring at at least one first position to which cuvettes in that ring can be rotated;

at least one reagent dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of a reagent to be used in testing from a reagent supply to a sample containing cuvette in one said ring at at least one second position to which cuvettes in that ring can be rotated;

a cuvette placement assembly having a supply of cuvettes and a cuvette delivery mechanism delivering cuvettes to at least one third position to which a cuvette receiving position in said cuvette holding ring can be placed by rotation of said cuvette holding ring in response to said control signals;

a cuvette extraction assembly extracting sample and reagent containing cuvettes from at least one fourth position to which a cuvette in said at least one cuvette holding ring can be placed by rotation of said ring in response to said control signals;

a scheduler of said control signals providing coordinated rotation of said at least first and second rings, sample and reagent dosing assemblies and cuvette placement and extraction assemblies for incubation of a sample and reagent in each cuvette for selectable incubation times and activation of the cuvette sample and reagent effector in said at least one second ring prior to extraction by said cuvette extraction assembly;

an indexing mechanism that positions the first and second rings relative to each other at any one of a plurality of positions corresponding to a number of cuvette receiving positions; and

an escapement associated with the indexing mechanism that indexes the relative position of the first and second rings by at least the distance between adjacent cuvette receiving positions in response to a trigger.

24. The incubation assembly of claim 23 wherein said trigger is a mechanical arm positioned to engage said escapement upon rotation of said escapement with the fist and second rings past said arm.

25. An incubation assembly for handling biological samples and test reagents in an automated biological testing system, said assembly comprising:

at least first and second ring segments, selectively associated for both fixed and independent rotation in response to control signals, at least one of which ring segments is adapted for holding sample cuvettes in spaced cuvette receiving positions and at least one other of said ring segments has a sample and reagent condition effector that is selectively applied to a biological sample and test reagent combination in said cuvettes by relative rotation of the first and second ring segments in response to said control signals;

at least one sample dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of a sample to be tested from a sample supply to a cuvette in said cuvette holding ring segment at least one first position to which cuvettes in that ring segment can be rotated;

at least one reagent dosing assembly responsive to said control signals and having a fluid transfer probe for applying a dose of a reagent to be used in testing from a reagent supply to a sample containing cuvette in said cuvette holding ring segment at least one second position to which cuvettes in that ring segment can be rotated;

a cuvette placement assembly having a supply of cuvettes and a cuvette delivery mechanism delivering cuvettes to at least one third position to which a cuvette receiving position in said cuvette holding ring segment can be placed by rotation of said cuvette holding ring segment in response to said control signals;

a cuvette extraction assembly extracting sample and reagent containing cuvettes from at least one fourth position to which a cuvette in said cuvette holding ring segment can be placed by rotation of said ring segment in response to said control signals;

an indexing mechanism positioning said at least first and second ring segments relative to each other at any one of a plurality of positions corresponding to a number of cuvette receiving positions;

an escapement associated with said indexing mechanism indexing the relative position of the first and second ring segments by at least the distance between adjacent cuvette receiving positions in response to a trigger; and

a scheduler of said control signals providing coordinated rotation of said at least first and second ring segments, sample and reagent dosing assemblies and cuvette placement and extraction assemblies for incubation of a sample and reagent in each cuvette for selectable incubation times and activation of the sample and reagent effector in said at least one second ring segment prior to extraction by said cuvette extraction assembly.

26. The incubation assembly of claim 25 wherein said trigger is a mechanical arm positioned to engage said escapement upon rotation of said escapement with the fist and second ring segments past said arm.