Verification device for optical clinical assay systems

• US 6,061,128 A
• Filed: 08/24/1998
• Issued: 05/09/2000
• Est. Priority Date: 09/04/1997
• Status: Expired due to Term

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Original Assignee: Avocet Medical, Inc. (Danaher Corporation)
• Inventors: Zweig, Stephen E., Meyer, Benjamin G., Downey, Thomas D.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Smith, Zandra V.
• Application Number:
  US09/138,824
• Time in Patent Office: 624 Days
• Field of Search: 356/243.1, 356/243.5, 356/445, 356/448, 250/252.1, 422/57, 422/58, 422/67, 422/68, 422/82.05, 436/46, 436/48
• US Class Current: 356/243.4
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04

Abstract

A device and method for verifying correct performance of an optical clinical assay system is provided.

Claims

1. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference;

an optical shutter disposed to pass an optical signal between the optical detection apparatus and the opaque optical reference, wherein the optical shutter is divided into a plurality of independently or semi-independently controlled pixel elements, such that the optical shutter modulates the intensity of the optical signal by varying the optical state of the shutter pixels in a time dependent manner; and

means for controlling the percent exposure of the optical reference to the optical detection apparatus to simulate a colorimetric, fluorescent, or luminescent test reagent;

wherein said controlling means controls the rate at which the optical reference is selectively revealed to the optical detection apparatus so as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent.

2. The device of claim 1, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

3. The device of claim 2, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

4. The device of claim 2 wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

5. The device of claim 1 wherein the optical shutter is electronically operated.

6. The device of claim 1, in which the optical shutter is a liquid crystal shutter, a magneto-optical shutter, a Faraday effect optical shutter, a thermochromic optical shutter, an electrochromic optical shutter, or a micro-mechanical optical shutter.

7. The device of claim 2, wherein the means for monitoring the temperature of the reaction stage is a thermocouple.

8. The device of claim 7, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

9. The device of claim 1, further comprising means to monitor the a reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

10. The device of claim 1, wherein the test reagent is thromboplastin.

11. The device of claim 1 further comprising means to monitor the temperature of a reaction stage of the clinical analytical system.

12. A verification device useful for determining the proper function of an optical, temperature controlled analytical instrument, the device comprising:

an electronic optical shutter with an optically active backing, interposed between an optical signal emitted by the analytical instrument and an optical detector mounted on the analytical instrument;

a temperature sensor, the sensor contacting a reaction stage on the analytical instrument; and

verification device electrodes, the verification device electrodes making contact with electrodes on the reaction stage of the analytical instrument;

wherein the action of the device is initiated by a resistance drop across the verification device electrodes, and wherein the optical transmission of the electronic optical shutter is modulated as a function of time and of the temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical instrument at various operating temperatures is simulated.

13. The verification device of claim 12, wherein the reaction stage is heated.

14. A verification device useful for determining the proper function of an optical, temperature controlled analytical instrument, the device comprising:

an optical shutter-fluorescent backing assembly comprising an optical shutter having a fluorescent backing placed on one side of the optical shutter;

the assembly being interposed between an optical signal emitted by the analytical instrument and an optical detector mounted on the analytical instrument;

a thermocouple in contact with a reaction stage on the analytical instrument; and

verification device electrodes, the verification device electrodes making contact with electrodes on the reaction stage of the analytical instrument;

wherein the action of the device is initiated by a resistance drop across the device electrode, and wherein the fluorescence of the optical shutter-fluorescent backing assembly is modulated as a function of time and of the temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical instrument at various operating temperatures is simulated.

15. The verification device of claim 14, wherein the reaction stage is heated.

16. An electronically controlled optical reference device, useful for the verification of an analytical instrument having an optical detection apparatus and using optically read reagent test strips, the device comprising:

an opaque optical reference, which simulates the optical characteristics of a reagent test strip after reaction with its intended clinical sample;

an optical shutter;

a means for controlling the percent exposure of the optical reference to the optical detection apparatus; and

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to mimic the reaction rates of one or more levels of clinical analytes reacting with a reagent test strip.

17. The device of claim 16, wherein the reagent is thromboplastin.

18. A method for verifying the temperature control of a clinical analytical system comprising an optical detection apparatus, the method comprising:

contacting the clinical analytical system with a verification device useful for determining the proper function of an optical, temperature controlled analytical instrument, the device comprising;

an electronic optical shutter with an optically active backing, interposed between an optical signal emitted by the analytical instrument and an optical detector mounted on the enzymatic analytical instrument;

a temperature sensor, the sensor contacting a reaction chamber on the analytical instrument; and

verification device electrodes, the verification device electrodes making contact with electrodes on the reaction chamber of the analytical instrument;

wherein the action of the device is initiated by a resistance drop across the verification device electrodes, and wherein the optical transmission of the electronic optical shutter is modulated as a function of time and of the temperature of the reaction chamber, wherein a range of levels of enzymatic activity measured by the analytical instrument at a range of operating temperatures is simulated, and

analyzing the optical reference;

wherein an expected result of analysis of the optical reference by the clinical analytical system is predictive of the correct operating temperature of the reaction chamber of the clinical analytical system.

19. A method for verifying the output of a system having a radiation source and a radiation detector, said method comprising:

positioning an opaque optical reference surface to receive radiation from the radiation source and return radiation to the detector; and

modulating at least one of the radiation from the source and the radiation to the detector over time in response to temperature changes.

20. A method as in claim 19, wherein the temperature changes are determined within the system.

21. A method as in claim 20, wherein the temperature changes are determined external to the system.

22. Apparatus for use in combination with an analyzer having a radiation source and a radiation detector, said apparatus comprising:

a reference surface which produces return radiation in response to receiving radiation from the source, and

means disposed adjacent the reference surface for modulating at least one of radiation to the reference surface or radiation from the reference surface, wherein the modulating means modulates the radiation over time to emulate reflective or radiation characteristics of a chemical or biological reaction on the reference surface.

23. Apparatus as in claim 22, wherein the modulation means modulates the radiation in response to changes in temperature.

24. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference comprising a fluorescent material;

an optical shutter having the optical reference on one side thereof, wherein a first optical signal of a first wavelength passes through the optical shutter and interacts with the fluorescence backing of the optical reference, and a fluorescence signal of a second wavelength passes back through the optical shutter;

means for controlling the percent exposure of the optical reference to the optical detection apparatus; and

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent.

25. The device of claim 24, wherein the opaque optical reference simulates a colorimetric, fluorescent, or luminescent reagent test strip.

26. The device of claim 24, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

27. The device of claim 26, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

28. The device of claim 26, wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

29. The device of claim 24, wherein the optical shutter is electronically operated.

30. The device of claim 24, in which the optical shutter is a liquid crystal shutter, a magneto-optical shutter, a Faraday effect optical shutter, a thermochromic optical shutter, an electrochromic optical shutter, or a micro-mechanical optical shutter.

31. The device of claim 28, wherein the means for monitoring the temperature of the reaction stage is a thermocouple.

32. The device of claim 31, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

33. The device of claim 31, further comprising means to monitor the reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

34. The device of claim 24, wherein the test reagent is thromboplastin.

35. The device of claim 24, further comprising means to monitor the temperature of a reaction stage of the clinical analytical system.

36. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference comprising a colored material;

an optical shutter having the optical reference on one side thereof, wherein a first optical signal consisting of a first spectrum of wavelengths passes through the optical shutter and interacts with the colored backing of the optical reference, and a second optical signal consisting of a subset of the first spectrum of wavelengths passes back through the optical shutter;

means for controlling the percent exposure of the optical reference to the optical detection apparatus; and

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent.

37. The device of claim 36, wherein the opaque optical reference simulates a colorimetric, fluorescent, or luminescent reagent test strip.

38. The device of claim 36, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

39. The device of claim 38, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

40. The device of claim 38, wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

41. The device of claim 36, wherein the optical shutter is electronically operated.

42. The device of claim 40, wherein the means for monitoring the temperature of the reaction stage is a thermocouple.

43. The device of claim 42, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

44. The device of claim 36, further comprising means to monitor the reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

45. The device of claim 36, wherein the test reagent is thromboplastin.

46. The device of claim 36, further comprising means to monitor the temperature of a reaction stage of the clinical analytical system.

47. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference comprising a luminescent material;

an optical shutter having a luminescent material on one side thereof, wherein the optical signal comprises a time increasing or time decreasing luminescence signal;

means for controlling the percent exposure of the optical reference to the optical detection apparatus; and

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent.

48. The device of claim 47, wherein the opaque optical reference simulates a colorimetric, fluorescent, or luminescent reagent test strip.

49. The device of claim 47, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

50. The device of claim 49, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

51. The device of claim 49, wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

52. The device of claim 47, wherein the optical shutter is electronically operated.

53. The device of claim 52, wherein the means for monitoring the temperature of the reaction stage is a thermocouple.

54. The device of claim 53, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

55. The device of claim 49, further comprising means to monitor the reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

56. The device of claim 47, wherein the test reagent is thromboplastin.

57. The device of claim 47, further comprising means to monitor the temperature of a reaction stage of the clinical analytical system.

58. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference;

an optical shutter;

means for controlling the percent exposure of the optical reference to the optical detection apparatus;

a thermocouple to measure the temperature of a reaction stage of the clinical analytical system; and

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent.

59. The device of claim 58, wherein the opaque optical reference simulates a colorimetric, fluorescent, or luminescent reagent test strip.

60. The device of claim 58, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

61. The device of claim 60, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

62. The device of claim 58, wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

63. The device of claim 58, wherein the optical shutter is electronically operated.

64. The device of claim 58, in which the optical shutter is a liquid crystal shutter, a magneto-optical shutter, a Faraday effect optical shutter, a thermochromic optical shutter, an electrochromic optical shutter, or a micro-mechanical optical shutter.

65. The device of claim 58, in which the optical shutter is divided into a plurality of independently or semi-independently controlled pixel elements, such that the optical shutter modulates the intensity of an optical signal by varying the optical state of the shutter pixels in a time dependent manner.

66. The device of claim 58, wherein the optical shutter comprises a fluorescent backing on one side of the optical shutter, and a first optical signal of a first wavelength passes through the optical shutter and interacts with the fluorescence backing, and a fluorescence signal of a second wavelength passes back through the optical shutter.

67. The device of claim 58, wherein the optical shutter comprises a colored backing on one side of the optical shutter, and a first optical signal consisting of a first spectrum of wavelengths passes through the optical shutter and interacts with the colored backing, and a second optical signal consisting of a subset of the first spectrum of wavelengths passes back through the optical shutter.

68. The device of claim 58, wherein the optical shutter comprises a luminescent backing on one side of the optical shutter, and the optical signal comprises a time increasing or time decreasing luminescence signal.

69. The device of claim 58, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

70. The device of claim 58, further comprising means to monitor the reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

71. The device of claim 58, wherein the test reagent is thromboplastin.

72. An electronically controlled optical reference device useful for the verification of a clinical analytical system having an optical detection apparatus, the reference device comprising:

an opaque optical reference;

an optical shutter;

means for controlling the percent exposure of the optical reference to the optical detection apparatus;

an algorithm or method that controls the rate at which the optical reference is selectively revealed to the optical detection apparatus, said algorithm or method being selected as to simulate the reaction rates of one or more levels of clinical analytes reacting with a test reagent; and

means to monitor the reagent present and/or blood present sensor on the clinical analytical device, wherein a stimulus to these sensors is provided to signal readiness of the meter for testing a clinical sample.

73. The device of claim 72, wherein the opaque optical reference simulates a colorimetric, fluorescent, or luminescent reagent test strip.

74. The device of claim 72, further comprising one or more first electrodes, wherein electrodes contact one or more second electrodes on a reaction stage of the clinical analytical system.

75. The device of claim 74, wherein electrical resistance across the electrodes in the reference device is modulated to simulate the addition or removal of a disposable reagent test strip or cartridge to the clinical analytical system.

76. The device of claim 74, wherein electrical resistance across the electrodes in the device is modulated to simulate the addition of a liquid sample to the clinical analytical system.

77. The device of claim 72, wherein the optical shutter is electronically operated.

78. The device of claim 72, in which the optical shutter is a liquid crystal shutter, a magneto-optical shutter, a Faraday effect optical shutter, a thermochromic optical shutter, an electrochromic optical shutter, or a micro-mechanical optical shutter.

79. The device of claim 72, in which the optical shutter is divided into a plurality of independently or semi-independently controlled pixel elements, such that the optical shutter modulates the intensity of an optical signal by varying the optical state of the shutter pixels in a time dependent manner.

80. The device of claim 72, wherein the optical shutter comprises a fluorescent backing on one side of the optical shutter, and a first optical signal of a first wavelength passes through the optical shutter and interacts with the fluorescence backing, and a fluorescence signal of a second wavelength passes back through the optical shutter.

81. The device of claim 72, wherein the optical shutter comprises a colored backing on one side of the optical shutter, and a first optical signal consisting of a first spectrum of wavelengths passes through the optical shutter and interacts with the colored backing, and a second optical signal consisting of a subset of the first spectrum of wavelengths passes back through the optical shutter.

82. The device of claim 72, wherein the optical shutter comprises a luminescent backing on one side of the optical shutter, and the optical signal comprises a time increasing or time decreasing luminescence signal.

83. The device of claim 82, wherein the means for monitoring the temperature of the reaction stage is a thermocouple.

84. The device of claim 83, wherein transparency of the optical shutter is modulated as a function of time and of a thermocouple monitored temperature of the reaction stage, wherein a range of levels of enzymatic activity measured by the analytical system at various operating temperatures is simulated.

85. The device of claim 72, wherein the test reagent is thromboplastin.

86. The device of claim 72, further comprising means to monitor the temperature of a reaction stage of the clinical analytical system.