Automatic immunochemistry analyzing apparatus and method

• US 5,296,195 A
• Filed: 10/02/1992
• Issued: 03/22/1994
• Est. Priority Date: 12/23/1985
• Status: Expired due to Term

• Current Assignee: Beckman Instruments, Inc. (Danaher Corporation)
• Original Assignee: Beckman Instruments, Inc. (Danaher Corporation)
• Inventors: Kan, Peter, Shibata, George K., Pang, Wings S.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Carpenter, Robert
• Application Number:
  US07/956,049
• Time in Patent Office: 536 Days
• Field of Search: 435/3, 435/4, 435/7.1, 435/808, 435/289, 435/290, 436/147, 436/909, 436/807-809, 436/536, 436/517, 422/68.1, 422/82.12, 422/109, 422/82.05
• US Class Current: 422/82.05
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 2201/122 Kinetic analysis; determining reaction rate
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 35/00 Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10S 436/909 Nephelometry

Abstract

A system for analyzing a chemical reaction provides control of the temperature and volume of the reagents to improve the accuracy and precision in quantitative measurements of specific proteins and other immunochemistries in body fluids. The reaction occurs in a cuvette within a nephelometric optics module. A sensor senses the temperatures of reaction buffer liquids as they flow into the cuvette, and a heat exchanging device increases or decreases the temperatures of the buffer liquids. A control circuit responsive to the temperature sensor controls the heat exchanging device to maintain the temperature of the buffer liquids and the cuvette within a selected temperature range. The system may also include a sample pickup station, a sample probe for withdrawing a selected sample from the sample pickup station, a sample preparation station, and transport device for carrying said sample from the sample preparation station to the reaction cuvette. The system may include an antibody pickup station, an antibody probe for withdrawing an antibody from the antibody pickup station, an antibody preparation station, and antibody transport device for carrying the antibody from the antibody preparation station to the reaction cuvette.

Claims

1. A system for analyzing a reaction between reagents, comprising:

a reaction cuvette for containing the reagents during the reaction;

first reagent delivery means for delivering a first reagent to said reaction cuvette;

second reagent delivery means for delivering a second reagent to said reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means and including means for selectively heating or cooling the cuvette to maintain the temperature in a predetermined temperature range, the reaction cuvette being for containing the reagents during the reaction;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent into the reaction cuvette, and means for selectively increasing or decreasing the temperature of the reagents independently of said cuvette to maintain the temperature of the reagent in a predetermined temperature range; and

means for analyzing the reaction between the reagents by processing the light scattered from the reaction in the reaction cuvette.

2. The system of claim 1 wherein said temperature controlling means includes:

first temperature sensor means for sensing the temperature of said reaction cuvette;

first heat pumping means for selectively increasing or decreasing the temperature of said reaction cuvette; and

means responsive to said first temperature sensor means for activating said first heat pumping means to maintain the temperature of said reaction cuvette within a selected temperature range.

3. The system of claim 2 wherein said temperature controlling means further includes:

second heat pumping means for selectively increasing or decreasing the temperatures of the reagents; and

means responsive to said second temperature sensor means for activating said second heat pumping means to maintain the temperature of the first and second reagents within the selected temperature range.

4. The system of claim 1 wherein said temperature controlling means further includes:

heat pumping means for selectively increasing or decreasing the temperatures of first and second reagents; and

means responsive to said temperature sensor means for activating said heat pumping means to maintain the temperature of the first and second reagents within a selected temperature range.

5. The system of claim 1 wherein said first and second temperature sensor means each comprises a thermistor means in thermal contact with the first and second reagents.

6. The system of claim 2 wherein said first heat pumping means comprises an electrically controlled heating and cooling device.

7. The system of claim 6 wherein said electrically controlled heating and cooling device is a Peltier effect device.

8. The system of claim 1 wherein the first reagent comprises an antigen and the second reagent comprises an antibody and said reaction cuvette is positioned within an nephelometer such that the reaction of the antigen and antibody may be monitored by processing light scattered from the reaction.

9. The system of claim 1 wherein said first reagent delivery means comprises:

a sample pick up station;

sample probe means for withdrawing a selected sample from said sample pick up station; and

sample transport means for carrying said sample probe from said sample pick up station to said reaction cuvette.

10. The system of claim 9 wherein said sample transport means comprises:

a rail;

a sample probe carriage slidably mounted on said rail;

first stepper motor means for controlling the position of said sample probe carriage along said rail; and

first position sensor means for sensing when said sample probe carriage is adjacent a first reference point fixed relative to said rail.

11. The system of claim 10 wherein said sample transport means further comprises stall sensor means for sensing operation of said first stepper motor.

12. The system of claim 10 wherein said sample transport means further comprises:

second stepper motor means mounted to said sample probe carriage for moving said sample probe means perpendicular to said rail, said sample probe means being movable between a retracted position for selectively establishing fluid communication with said sample station, said reaction cuvette and a sample probe wash station and an extended position for moving said sample probe means between said sample station, said reaction cuvette and said sample probe wash station; and

second position sensor means for sensing when said sample probe means is in said extended position.

13. The system of claim 1 wherein said second reagent delivery means comprises:

an antibody pick up station;

antibody probe means for withdrawing an antibody from said antibody pick up station; and

antibody transport means for carrying said antibody from said antibody pick up station to said reaction cuvette.

14. The system of claim 10 wherein said sample transport means comprises stall sensor means for sensing operation of a first stepper motor.

15. The system of claim 10 wherein said sample is an antibody and said antibody transport means comprises;

said rail;

an antibody probe carriage slidably mounted on said rail;

third stepper motor means for controlling the position of said antibody probe carriage along said rail; and

third position sensor means for sensing when said antibody probe carriage is adjacent a second reference point fixed relative to said rail.

16. The system of claim 15 wherein said antibody transport means further comprises;

fourth stepper motor means mounted to said antibody probe carriage for moving said antibody probe means perpendicular to said rail, said antibody probe means being movable between a retracted position for selectively establishing fluid communication with said antibody pickup station, said reaction cuvette and a antibody probe wash station and an extended position for moving said antibody probe means between said antibody station, said reaction cuvette and said antibody probe wash station; and

fourth position sensor means for sensing when said antibody probe means is in said extended position.

17. A system for analyzing a reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means and selectively heating or cooling the cuvette to maintain the temperature in a predetermined temperature range;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent into the reaction cuvette and selectively increasing or decreasing the temperature of the reagents independently of said cuvette to maintain the temperature of the reagents in a predetermined temperature range;

means for injecting an antigen reagent and an antibody reagent into the reaction cuvette for containing the reagents during the reaction wherein the means for injecting the reagent includes;

(a) means for aspirating a selected antigen reagent sample into a sample probe from a sample pick up station;

(b) means for automatically transporting said sample from said sample pick up station to said reaction cuvette;

(c) means for aspirating an antibody reagent from an antibody pick up station into an antibody probe means; and

(d) means for transporting the antibody from the antibody pick up station to said reaction cuvette; and

means for monitoring the reaction of the antigen and antibody by processing light scattered from the reaction in a nephelometer.

18. A system for analyzing a light scattering reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting reagents into the reaction cuvette;

means for selectively increasing or decreasing the temperatures of at least one of the reagents and the reaction cuvette independently of the other to maintain the temperature in a predetermined range;

means for combining different quantities of a diluent with a sample reagent and establishing different concentrations of sample reagent;

means for providing a range of different buffers and transferring a selected buffer to the reaction cuvette;

means for injecting selected reagents into the reaction cuvette; and

means for analyzing the reaction between the reagents by processing the light scattered from the reaction in the reaction cuvette.

19. A system for analyzing a reaction between reagents in a nephelometer, comprising:

a reaction cuvette means for sensing the temperature of the reaction cuvette with first temperature sensor means and selectively heating or cooling the cuvette to maintain the temperature in a predetermined temperature range, the reaction cuvette being for containing the reagents during the reaction;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent into the reaction cuvette, and selectively increasing or decreasing the temperature of the reagents independently of said cuvette to maintain the temperature in a predetermined temperature range;

means for combining different quantities of a diluent with a selected antigen reagent sample and establishing different concentrations of the sample;

means for providing a range of different reaction buffers and transferring a selected reaction buffer to the reaction cuvette via the reagent delivery means;

means for injecting an antigen reagent and an antibody reagent into the reaction cuvette, wherein the means for injecting the reagents include;

(a) means for aspirating a selected concentration of the antigen reagent sample into a sample probe from a sample pick up station,

(b) means for transporting said sample from said sample pick up station to said reaction cuvette,

(c) means for aspirating an antibody reagent from an antibody pick up station into an antibody probe means, and

(d) means for transporting the antibody from the antibody pick up station to said reaction cuvette; and

means for monitoring the reaction of the antigen and antibody by processing light scattered from the reaction in the reaction cuvette.

20. A system for analyzing a light scattering reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of a reaction cuvette with first temperature sensor means;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent to the reaction cuvette;

means for selectively increasing or decreasing the temperature independently of at least one of the reagents and reaction cuvette to maintain the temperature in a predetermined temperature range;

means for combining different quantities of a diluent with a sample reagent and establishing different concentrations of sample reagent;

means for injecting selected reagents into the reaction cuvette; and

means for analyzing the reaction between the reagents by processing the light scattered from the reaction in the reaction cuvette.

21. A system for analyzing a reaction between reagents in a nephelometer comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means and selectively heating or cooling the cuvette to maintain the temperature in a predetermined temperature range, the reaction cuvette being for containing reagents during the reaction;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent into the reaction cuvette and selectively increasing or decreasing the temperature of the reagents independently of the cuvette to maintain the temperature in a predetermined temperature range;

means for combining different quantities of a diluent with a selected antigen reagent sample and establishing different concentrations of the sample;

means for injecting an antigen reagent and an antibody reagent into the reaction cuvette for containing the reagents during the reaction wherein means for injecting the reagent, includes;

(a) means for aspirating a selected antigen reagent sample into a sample probe from a sample pick up station,

(b) means for transporting said sample from said sample pick up station to said reaction cuvette,

(c) means for aspirating an antibody reagent from an antibody pick up station into an antibody probe means, and

(d) means for transporting the antibody from the antibody pick up station to said reaction cuvette; and

means for monitoring the reaction of the antigen and antibody by processing light scattered from the reaction in the reaction cuvette.

22. A system for analyzing a light scattering reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means, the reaction cuvette being for containing the reagents during the reaction;

means for sensing the temperature of reagent with second temperature sensor means;

means for selectively increasing or decreasing the temperature of at least one of the reagents and reaction cuvette independently to maintain the temperature in a predetermined temperature range;

means for providing a range of different reaction buffers and transferring a selected reaction buffer to the reaction cuvette;

means for injecting reagents into the reaction cuvette; and

means for analyzing the reaction between the reagents by processing the light scattered from the reaction in the reaction cuvette.

23. A system for analyzing a reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means and selectively heating or cooling the cuvette to maintain the temperature in a predetermined temperature range, the reaction cuvette being for containing the reagents during the reaction;

means for sensing the temperature of reagents with second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting at least one reagent into the reaction cuvette and selectively increasing or decreasing the temperature of the reagents independently of the cuvette to maintain the temperatures in a predetermined temperature range;

means for providing a range of different buffers and transferring a selected reaction buffer to the reaction cuvette via the reagent delivery means;

means injecting an antigen reagent and an antibody reagent into the reaction cuvette for containing the reagents during the reaction wherein the means for injecting the reagents, includes;

(a) means for aspirating a selected antigen reagent sample into a sample probe from a sample pick up station,

(b) means for transporting said sample from said sample pick up station to said reaction cuvette,

(c) means for aspirating an antibody reagent from an antibody pick up station into an antibody probe means, and

(d) means for transporting the antibody from the antibody pick up station in said reaction cuvette; and

means for monitoring the reaction of the antigen and antibody by processing light scattered from the reaction in the reaction cuvette.

24. A system for analyzing a light scattering reaction between reagents in a nephelometer, comprising:

a reaction cuvette;

means for sensing the temperature of the reaction cuvette with first temperature sensor means, the reaction cuvette being for containing reagents during the reaction;

means for sensing the temperature of reagents with a second temperature sensor means, the reagents being delivered by a reagent delivery means for injecting reagents to the reaction cuvette;

means for selectively increasing or decreasing the temperature of at least one of the reagents and the reaction cuvette independently of the other;

means for providing a range of different diluents to a sample reagent and establishing different concentrations of sample reagent;

means for providing a range of different buffers and transferring a selected reaction buffer to the reaction cuvette;

means for injecting selected reagents into the reaction cuvette; and

means for analyzing the reaction between the reagents by processing the light scattered from the reaction in the reaction cuvette.