Multichambered container and instrument for performing diagnostic tests

• US 5,149,501 A
• Filed: 01/29/1990
• Issued: 09/22/1992
• Est. Priority Date: 01/29/1990
• Status: Expired due to Fees

• Current Assignee: Cirrus Diagnostics, Inc. (Siemens AG)
• Original Assignee: Cirrus Diagnostics, Inc. (Siemens AG)
• Inventors: Palmieri, Thomas, Babson, Arthur L., Olson, Douglas R.
• Primary Examiner(s): Hill, Jr., Robert J.
• Application Number:
  US07/471,416
• Time in Patent Office: 967 Days
• Field of Search: 436/45, 436/808, 436/807, 422/101, 422/64, 422/58, 422/72, 422/61, 422/102, 422/100, 494/10, 435/287-288, 435/296-298, 435/975
• US Class Current: 422/404
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 2035/00504 combined with carousels
• CPC Class Codes: G01N 2035/0446 Combinations of the above
• CPC Class Codes: G01N 21/07 Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: G01N 35/00594 Quality control, including calibration or testing of components of the analyser
• CPC Class Codes: G01N 35/00693 Calibration
• CPC Class Codes: G01N 35/025 having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/10 Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence
• CPC Class Codes: G01N 35/1004 Cleaning sample transfer devices
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/111666 Utilizing a centrifuge or compartmented rotor

Abstract

An instrument (50) automatically determines the concentrations of HDL cholesterol, LDL cholesterol, total cholesterol and triglycerides for a sample (80) of whole, anticoagulated blood placed in a doughnut shaped container (10). The sample (80) is first separated into its blood cell and plasma (84) constituents using high speed centrifugation (54) and a thixotropic gel (82). Part of the plasma (84) is then deposited in an HDL separation chamber (14) where LDL cholesterol and VLDL cholesterol are precipitated by a reagent and the precipitant is sedimented by high speed centrifugation (54) against V-shaped grooves (40) in the outermost wall (38) of the HDL separation chamber (14). Part of the plasma (84) is diluted ten-fold. The supernatant in the HDL separation chamber is then placed in a cuvette reaction chamber (b 18) where it reacts with a cholesterol reagent. The diluted plasma is placed in two other cuvette reaction chambers (18) where it reacts with chloesterol and triglycerides reagents, respectively. Calibration reagents, stored in storage chambers (20), react in two other cuvette reaction chambers (18) to establish a reference absorbance. A pipettor (58) handles all the fluid transfers in the doughnut shaped container (10) and operates in conjunction with a slow speed motor (56) that precisely moves the spindle (52) on which the doughnut shaped container (10) is mounted. A colorimetric measuring system (70, 72, and 74) monitors the absorbance of chemical reactions occurring in the cuvette chambers (18).

Claims

1. A multichambered container adapted to be rotated about a longitudinal axis through said container for determining the concentration of plasma constituents, comprising:

a plurality of chambers integrally formed in said container, each of said chambers defined by a plurality of walls, each of said chambers being non-communicable with each other and said chambers being accessible by a pipetter;

a means for separating plasma from a whole blood sample positioned in a first chamber;

a reagent positioned in a second chamber for reacting with a constituent of said plasma separated from said whole blood sample; and

windows positioned in a chamber in said multichambered container for allowing optical monitoring of a reaction occurring in said chamber, whereby rotation about said longitudinal axis through said container causes separation of said plasma from said whole blood sample with said means for separating.

2. A multichambered container as recited in claim 1 wherein said reagent reacts with cholesterol.

3. A multichambered container as recited in claim 1 wherein said reagent reacts with triglycerides.

4. A multichambered container as recited in claim 1 wherein said reagent reacts with glucose.

5. A multichambered container as recited in claim 1 wherein said reagent reacts with lactate dehydrogenase.

6. A multichambered container as recited in claim 1 wherein said plurality of walls defining said first chamber comprise an inside wall, an outside wall, and a pair of side walls connected between said inside wall and said outside wall, a space between said side walls being narrower at said outside wall than at said inside wall.

7. A multichambered container as recited in claim 1 wherein said windows are integrally formed with sad walls of said second chamber.

8. A multichambered container adapted to be rotated about a longitudinal axis through said container for determining the concentration of plasma constituents, comprising:

a plurality of chambers integrally formed in said container, each of said chambers defined by a plurality of walls, each of said chambers being non-communicable with each other and said chambers being accessible by a pipetter;

a thixotropic gel positioned in a first chamber for separating plasma from a whole blood sample;

a first reagent positioned in a second chamber for reacting with a first constituent of said plasma separated from said whole blood sample; and

windows positioned in a chamber in said multichambered container for allowing optical monitoring of a reaction occurring in said chamber, whereby rotation about said longitudinal axis through said container causes separation of said plasma from said whole blood sample with said thixotropic gel.

9. A multichambered container as recited in claim 8 wherein said first reagent reacts with cholesterol.

10. A multichambered container as recited in claim 8 wherein said first reagent reacts with triglycerides.

11. A multichambered container as recited in claim 8 wherein said first reagent reacts with glucose.

12. A multichambered container as recited in claim 8 wherein said first reagent reacts with lactate dehydrogenase.

13. A multichambered container as recited in claim 8 wherein said plurality of walls defining said first chamber comprise an inside wall, an outside said inside wall and said outside wall, a space between said side walls being narrower at said outside wall than at said inside wall.

14. A multichambered container as recited in claim 8 wherein said windows are integrally formed with said walls of said second chamber.

15. A multichambered container as recited in claim 8 further comprising a means for separating a high density lipoprotein cholesterol constituent of said plasma separated from said whole blood sample from both a low density lipoprotein cholesterol and a very low density lipoprotein cholesterol constituent of said plasma separated from said whole blood sample positioned in a third chamber.

16. A multichambered container as recited in claim 15 wherein said means for separating said high density lipoprotein cholesterol constituent of said plasma separated from said whole blood sample from both said low density lipoprotein cholesterol and said very low density lipoprotein cholesterol constituents of said plasma separated from said whole blood sample comprises a precipitating reagent which precipitates said low density lipoprotein cholesterol and said very low density lipoprotein cholesterol constituents from said plasma separated from said whole blood sample.

17. A multichambered container as recited in claim 16 wherein said plurality of walls defining said third chamber comprise an inside wall, an outside wall, and a pair of side walls connected between said inside wall and said outside wall, said outside wall including grooves for holding a precipitant thereagainst.

18. A multichambered container as recited in claim 15 further comprising a second reagent positioned in a fourth chamber for reacting with said high density lipoprotein cholesterol constituent of said plasma separated from said whole blood sample.

19. A multichambered container as recited in claim 18 wherein said first reagent reacts with triglycerides.

20. A multichambered container as recited in claim 18 wherein said first reagent reacts with cholesterol.

21. A multichambered container as recited in claim 18 further comprising windows integrally formed with walls defining said fourth chamber.

22. A multichambered container as recited in claim 8 further comprising a second reagent positioned in a third chamber for reacting with a second constituent of said plasma separated from said whole blood sample, said second constituent being different from said first constituent, said third chamber having optical windows positioned in said walls through which a chemical reaction in said third chamber can be monitored.

23. A multichambered container as recited in claim 22 wherein said first reagent reacts with cholesterol and said second reagent reacts with triglycerides.

24. A multichambered container as recited in claim 22 wherein said optical windows in said third chamber are integrally formed with said walls.

25. A multichambered container as recited in claim 8 further comprising a first calibrating solution having a known concentration of said first constituent of said plasma separated from said whole blood sample positioned in a third chamber, a fourth chamber having optical windows positioned in said walls through which a chemical reaction in said fourth chamber can be monitored, and a quantity of said first reagent being positioned in said fourth chamber for reacting with said calibrating solution having said known concentration of said first constituent.

26. A multichambered container as recited in claim 25 wherein said optical windows in said fourth chamber are integrally formed with said walls.

27. A multichambered container as recited in claim 25 wherein said first reagent reacts with triglycerides.

28. A multichambered container as recited in claim 25 wherein said first reagent reacts with cholesterol.

29. A multichambered container as recited in claim 25 comprising a second reagent positioned in a fifth chamber for reacting with a second constituent of said plasma separated from said whole blood sample, said second constituent being different from said first constituent, said fifth chamber having optical windows positioned in said walls through which a chemical reaction in said fifth chamber can be monitored, a second calibrating solution having a known concentration of said second constituent of said plasma separated from said whole blood sample positioned in a sixth chamber, a seventh chamber having optical windows positioned in said walls through which a chemical reaction in said seventh chamber can be monitored, and a quantity of said second reagent being positioned in said seventh chamber for reacting with said calibrating solution having said known concentration of said second constituent.

30. A multichambered container as recited in claim 29 wherein said first reagent reacts with cholesterol and said second reagent reacts with triglycerides.

31. A multichambered container as recited in claim 29 wherein said first and second calibrating solutions are the same and include known concentrations of cholesterol and glycerol.

32. A multichambered container as recited in claim 29 wherein said optical windows in said fifth and seventh chambers are integrally formed with said walls.

33. A multichambered container as recited in claim 8 further comprising a lid affixed to said container, said lid having a plurality of openings providing access to each of said plurality of chambers.

34. A multichambered container as recited in claim 33 further comprising membranes adhered over each of said openings in said lid.

35. A multichambered container as recited in claim 34 wherein each of said membranes are comprised of a rubber coated plastic.

36. A multichambered container as recited in claim 33 wherein said lid is affixed by an ultrasonic weld.

39. An instrument as recited in claim 28 wherein said low speed motor is capable of precisely positioning each of said chambers of said multichambered container on said spindle relative to said pipettor needle, said pipettor needle translatable on a Z-axis.

37. An instrument for performing diagnostic tests on a patient'"'"'s whole blood sample, comprising:

a multichambered container positioned on a spindle comprising a plurality of chambers integrally formed in said container, each of said chambers defined by a plurality of walls, each of said chambers being noncommunicable with each other and said chambers being accessible by a pipetter, a thixotropic gel positioned in a first chamber for separating plasma from a whole blood sample, and a reagent positioned in a second chamber for reacting with a constitutent of said plasma separated from said whole blood sample, and windows positioned in a chamber in said multichambered container for allowing optical monitoring of a reaction occurring in said chamber;

a means for rotating said spindle at both high and low speeds;

a pipettor having a needle translatable into and out of at least one of said chambers of said multichambered container, said pipettor capable of retrieving fluid from one of said chambers and dispensing said fluid into another of said chambers;

a monitoring system positioned to monitor said chemical reaction in said second chamber; and

a means for determining a concentration value for said constituent of said plasma separated from said whole blood sample from data output from said monitoring system.

38. An instrument as recited in claim 37 wherein said means for rotating said spindle comprises both high speed and low speed motors, said high speed and low speed motors being alternatively connectable to said spindle for rotating said spindle.

40. An instrument as recited in claim 37 wherein said monitoring system comprises a light source, a reference detector, and a measurement detector, said measurement detector detecting light which passes through said windows in said chamber having said windows in said container, said reference detector detecting light which does not pass through said windows in said chamber.

41. An instrument as recited in claim 40 wherein said light source is positioned in a hub inside said spindle and said measurement detector is positioned in a chassis, said multichambered container positioned to rotate with said spindle such that said plurality of chambers pass between an optical path between said light source and said measurement detector.

42. A multichambered container adapted to be rotated about a longitudinal axis through said container for determining the concentration of plasma constituents, comprising:

a plurality of chambers integrally formed in said container, each of said chambers defined by a plurality of walls, each of said chambers being non-communicable with each other and said chambers being accessible by a pipetter;

a separation chamber including a means for separating a first constituent from a biological fluid by centrifugation;

a reagent positioned in a reagent chamber for reacting with a second constituent in said biological fluid; and

windows positioned in a chamber in said multichambered container for allowing optical monitoring of a reaction occurring in said chamber, whereby rotation about said longitudinal axis through said container causes separation of said first constituent from said biological fluid.

43. A multichambered container as recited in claim 42 wherein said means for separating in said chamber includes a means for collecting a precipitate on an outward wall under a centrifugal force.

44. A multichambered container as recited in claim 43 wherein said biological fluid is blood plasma and said first constituent is low density lipoprotein cholesterol and said second constituent is high density lipoprotein cholesterol.

45. A multichambered container as recited in claim 42 wherein said windows are integrally formed with the walls of said reagent chamber.

46. A multichambered container as recited in claim 42 further comprising a calibrating solution positioned in a calibrant chamber, said calibrating solution calibrating for said second constituent.

47. A multichambered container as recited in claim 42 further comprising a diluting solution positioned in a diluent chamber.