Device for chromatographic quantitative measurement

• US 20030054567A1
• Filed: 08/22/2002
• Published: 03/20/2003
• Est. Priority Date: 09/25/2000
• Status: Active Grant

• Current Assignee: PHC Holdings Corporation
• Original Assignee: Panasonic Corporation (Panasonic Holdings Corporation)
• Inventors: Aga, Masahiro, Miyoshi, Koji, Shigematsu, Kaoru
• Granted Patent: US 7,678,566 B2
• Time in Patent Office: Days
• US Class Current: 436/514
• 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
• CPC Class Codes: G01N 30/90 Plate chromatography, e.g. thin layer or paper chromatography
• CPC Class Codes: G01N 30/95 Detectors specially adapted therefor; Signal analysis
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: Y10S 435/967 Standards, controls, materials, e.g. validation studies, buffer systems
• CPC Class Codes: Y10S 435/97 Test strip or test slide
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

In a chromatography quantitative measuring apparatus according to the present invention, a beam applied from a light source (201) to a chromatography test strip (8) is formed into an elliptical shape by an optical means such as a cylindrical lens (205), a variation in absorbance that accompanies elution of a marker regent is detected while the elliptical beam is applied between a marker reagent hold part (82) and a detection part (83), and a measurement is automatically started in a prescribed period of time since the detection of variation.

According to the chromatography quantitative measuring apparatus so configured, non-uniform coloration is reduced by shaping the beam elliptically with the optical means, whereby the accuracy of quantitative analysis is enhanced, and further the apparatus can be operated easily.

Claims

1. A chromatography quantitative measuring apparatus which applies a beam emitted from a light source to a sample, detects an optical signal from a transmitted light or reflected light from the sample, and quantitatively reads the concentration of the sample from the signal, including:

an optical means for forming the beam emitted from the light source into an elliptical or rectangular shape and applying the elliptically or rectangularly shaped beam to the sample.

2. The chromatography quantitative measuring apparatus as defined in claim 1, wherein

the sample is put on an immuno-chromatography test strip, and

the beam applied to the sample has a longer side which is shorter than the width of the immuno-chromatography test strip in the width direction that is orthogonal with respect to the long-side direction.

3. The chromatography quantitative measuring apparatus as defined in claim 1, wherein

the sample is put on an immuno-chromatography test strip, and

the beam applied to the sample has a shorter side which is shorter than the width of a detection part region of the immuno-chromatography test strip.

4. The chromatography quantitative measuring apparatus as defined in any of claims 1 to 3, wherein

the optical signal is detected by scanning the beam applied to the sample, or the sample.

5. The chromatography quantitative measuring apparatus as defined in claim 1, wherein

a laser is used as the light source, and a laser beam from the light source is converted into a collimated beam via a collimator lens, and

the optical means forms the collimated beam into an elliptical shape via a cylindrical lens and applies the elliptically shaped beam to the sample.

6. The chromatography quantitative measuring apparatus as defined in claim 1, wherein

a laser is used as the light source, and the laser beam from the light source is converted into a collimated beam via a collimator lens, and

the optical means forms the collimated beam into a rectangular shape via a rectangularly shaped aperture member and applies the rectangularly shaped beam to the sample.

9. The chromatography quantitative measuring apparatus as defined in any of claims 5 to 8, including:

a compensation means for storing the initial wavelength of the laser, calculating the present wavelength of the laser to compensate by provision of a temperature detection element in the vicinity of the laser, and compensating an optical signal detection value or the converted concentration of the sample which is obtained by converting the optical signal detection value.

10. The chromatography quantitative measuring apparatus as defined in claim 9, wherein

the compensation means performs processing for detecting the optical signal, processing for obtaining the converted concentration of the sample, and processing for compensating the converted concentration, with the same calculator.

11. The chromatography quantitative measuring apparatus as defined in any of claims 5 to 8, wherein

the concentration of the sample is calculated from a difference between electronic signals obtained by two light receiving elements, i.e., a reference beam light receiving element which receives a reference beam separated from the beam emitted from the laser, and a scattering light receiving element which receives a scattering light generated by the application of the laser to the sample, and

the area of the reference beam light receiving element for receiving light is smaller than the area of the scattering light receiving element for receiving light.

12. The chromatography quantitative measuring apparatus as defined in any of claims 5 to 8, wherein

the concentration of the sample is calculated from a difference between electronic signals obtained by two light receiving elements, i.e., a reference beam light receiving element which receives a reference beam separated from the beam emitted from the laser, and a scattering light receiving element which receives a scattering light generated by the application of the laser to the sample, including:

a condensing means for condensing the scattering light from the sample on the scattering light receiving element.

13. The chromatography quantitative measuring apparatus as defined in claim 12, wherein

the condensing means is a concave mirror which condenses a light from the sample that is scattered in the opposite direction of the direction in which the scattering light receiving element is arranged, on the scattering light receiving element.

14. The chromatography quantitative measuring apparatus as defined in claim 12, wherein

the condensing means is a condensing lens arranged between the sample and the scattering light receiving element, which condenses the scattering light from the sample that goes toward the scattering light receiving element, on the scattering light receiving element.

7. A chromatography quantitative measuring apparatus which applies a beam emitted from a light source to a sample, detects an optical signal from a transmitted light or reflected light from the sample, and quantitatively reads the concentration of the sample from the signal, including:

a laser as the light source; and

a collimator lens which converts the laser beam into a collimated beam, wherein

when the collimated beam is shaped rectangularly via an aperture member and the rectangularly shaped beam is applied to the sample, the direction of a longer side of the rectangularly shaped beam is made to correspond to the direction in which the beam divergence angle of the laser becomes larger.

8. A chromatography quantitative measuring apparatus which applies a beam emitted from a light source to a sample, detects an optical signal from a transmitted light or reflected light from the sample, and quantitatively reads the concentration of the sample from the signal, including:

a laser as, the light source; and

a collimator lens which converts the laser beam into a collimated beam, wherein

when the collimated beam is shaped elliptically via a cylindrical lens and the elliptically shaped beam is applied to the sample, the direction of a longer side of the elliptically shaped beam is made to correspond to the direction in which the beam divergence angle of the laser becomes larger.

15. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

the inspection target solution is applied to the chromatography test strip, the optical beam is applied to a prescribed position of the base part, a variation of the transmitted light or reflected light from the chromatography test strip, which is generated by the elution of the marker reagent that accompanies the development of the inspection target solution, is detected, and the concentration of the analysis target included in the inspection target solution is measured in a prescribed period of time since the detection of variation.

16. The chromatography quantitative measuring apparatus as defined in claim 15, wherein

at least one of temperature and humidity is monitored, and a previously set prescribed period of time after which the measurement of the concentration of the analysis target is performed is compensated.

17. The chromatography quantitative measuring apparatus as defined in claim 15, wherein

the light source is repeatedly lighted and extinguished alternately while the development of the inspection target solution is detected.

18. The chromatography quantitative measuring apparatus as defined in claim 15, wherein

the light source is extinguished until shortly before the detection of the development of the inspection target solution.

19. The chromatography quantitative measuring apparatus as defined in claim 15, wherein

output from the light source is set lower than that when the concentration of the analysis target is measured, while the development of the inspection target solution is detected.

20. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

the inspection target solution is applied to the chromatography test strip, a speed of development after the application of the inspection target solution is detected, and it is judged whether performance of the chromatography test strip is high or low from the speed of development.

21. The chromatography quantitative measuring apparatus as defined in claim 20, wherein

the speed of development is calculated by detecting time variation of value of a detection signal, which is generated by the flow of the marker reagent that accompanies the development of the inspection target solution on the chromatography test strip.

22. The chromatography quantitative measuring apparatus as defined in claim 20, wherein

the speed of development is calculated from a speed of scanning of the optical beam, when the optical beam is scanned so that a value of the detection signal, which is generated by the elution of the marker reagent that accompanies the development of the inspection target solution on the chromatography test strip, is kept constant.

23. The chromatography quantitative measuring apparatus as defined in claim 20, wherein

a discrimination value of the speed of development, from which whether performance of the chromatography test strip is high or low is judged, is compensated from a result of measuring at least one of surrounding temperature and humidity at the development of the inspection target solution on the chromatography test strip.

24. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

a kind of inspection target solution is judged from a detection signal at the base part on the chromatography test strip where the inspection target solution is applied.

25. The chromatography quantitative measuring apparatus as defined in claim 24, wherein

the base part where the detection signal is measured is located downstream of the detection part in the direction of the development.

26. The chromatography quantitative measuring apparatus as defined in claim 24, wherein

a calibration curve in conformity with the inspection target solution can be selected previously.

27. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

deficiency in the amount of inspection target solution applied and insufficient development on the chromatography test strip are judged from a detection signal that is obtained by applying the optical beam to the downstream end part of the base part on the chromatography test strip where the inspection target solution is applied.

28. The chromatography quantitative measuring apparatus as defined in claim 27, wherein

the optical beam is scanned from the upstream end part of the base part on the chromatography test strip to the downstream end part thereof.

29. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

when a detection signal at a part downstream of the detection part in the direction of the development, where influence of the detection part is not exerted, is a standard value, a detection signal at the detection part is taken as a detection signal for the measurement of concentration.

30. The chromatography quantitative measuring apparatus as defined in claim 29, wherein

the detection signal for the measurement of concentration is an average value of values about an extreme value of the detection part, and the detection signal as the standard value is an average value of values in the vicinity of the position downstream of the detection part in the direction in which the inspection target solution is developed, where influence of the detection part is not exerted.

31. The chromatography quantitative measuring apparatus as defined in claim 29, wherein

the detection signal for the measurement of concentration is an intermediate value of values about an extreme value of the detection part, and the detection signal as the standard value is an intermediate value of values in the vicinity of the position downstream of the detection part in the direction in which the inspection target solution is developed, where influence of the detection part is not exerted.

32. The chromatography quantitative measuring apparatus as defined in claim 29, wherein

a comparison is made of values about an extreme value of the detection signal at the detection part, and when a difference therebetween exceeds a discrimination value, the chromatography test strip is judged to be low in performance.

33. The chromatography quantitative measuring apparatus as defined in claim 29, wherein

a comparison is made of values in the vicinity of a position downstream of the detection part in the direction of the development, where influence of the detection part is not exerted, and when a difference therebetween exceeds a discrimination value, the chromatography test strip is judged to be low in performance.

34. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

the measurement of concentration is performed on the chromatography test strip exclusive of the marker reagent hold part.

35. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

a region on the chromatography test strip where a value of the detection signal is flat is taken as a region of the marker reagent hold part.

36. The chromatography quantitative measuring apparatus as defined in claim 35, wherein

the width of the region on the chromatography test strip where the value of the detection signal is flat is calculated, and the width is compared with a prescribed width of the marker reagent hold part.

37. The chromatography quantitative measuring apparatus as defined in claim 35, wherein

a value in the region on the chromatography test strip where the detection signal is flat is detected, and the amount of residual marker reagent is confirmed from the detected value.

38. A chromatography quantitative measuring apparatus which applies an optical beam emitted from a light source to a chromatography test strip that comprises an application part where an inspection target solution is applied;

a marker reagent hold part which holds a marker reagent that can be eluted by development of the inspection target solution;

a base part where a specific binding reaction is caused between the marker reagent and an analysis target included in the inspection target solution; and

a detection part where a bounded material of the marker reagent and the analysis target is immobilized, detects an optical signal utilizing a transmitted light or reflected light from the chromatography test strip, and quantitatively measures the concentration of the analysis target included in the inspection target solution from the signal, wherein

a rise and fall of a detection signal are recognized, and an extreme value of the detection signal is obtained.

39. The chromatography quantitative measuring apparatus as defined in claim 38, wherein

the rise and fall of the detection signal is recognized, an interval between the rise and the fall is calculated, and the size of the interval is compared with a prescribed width of the detection part.

40. A chromatography quantitative measuring apparatus for performing a quantitative measurement by applying an inspection target solution to an immuno-chromatography test strip, applying a beam to a detection part of the immuno-chromatography test strip after development of the inspection target solution, so as to detect an optical signal, and quantitatively reading the concentration of a sample from the detected signal, including:

a fixing table for holding the immuno-chromatography test strip and a measurement table for holding the fixing table, wherein

the immuno-chromatography test strip comprises a development layer for developing the inspection target solution and a carrier for holding the development layer.

41. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the measurement table is provided with a groove for positioning the fixing table.

42. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the measurement table is provided with a movable projection for fixing the fixing table.

43. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the quantitative measurement is performed by scanning the beam.

44. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is provided with a projection, and the carrier is provided with a hole in which the projection can be inserted.

45. The chromatography quantitative measuring apparatus as defined in claim 44, wherein

the hole has a round shape.

46. The chromatography quantitative measuring apparatus as defined in claim 44, wherein

the hole has a rectangular shape.

47. The chromatography quantitative measuring apparatus as defined in claim 44, wherein

the hole is provided downstream of the development layer in the direction in which the inspection target solution is developed.

48. The chromatography quantitative measuring apparatus as defined in claim 44, wherein

the hole is provided asymmetrically with respect to the center line of the immuno-chromatography test strip in the longer-side direction.

49. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is provided with a guide, and

the carrier is larger than the development layer and follows the shape of the guide.

50. The chromatography quantitative measuring apparatus as defined in claim 49, wherein

a part of the guide is inclined.

51. The chromatography quantitative measuring apparatus as defined in claim 49, wherein

the carrier is provided with a notch in which the guide can be inserted.

52. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the measurement table is provided with a projection, and

the immuno-chromatography test strip and the fixing table are provided with holes in which the projection can be inserted.

53. The chromatography quantitative measuring apparatus as defined in claim 52, wherein

the projection has its end inclined.

54. The chromatography quantitative measuring apparatus as defined in claim 40, including:

a test strip fixing device for fixing the immuno-chromatography test strip on the fixing table, wherein

the test strip fixing device presses the vicinity of a measurement area of the immuno-chromatography test strip.

55. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device presses the carrier of the immuno-chromatography test strip.

56. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device is provided with a transmission window through which the beam is transmitted.

57. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device is provided with pawl-shaped projections for fixing the test strip fixing device on the fixing table.

58. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device slides along the fixing table.

59. The chromatography quantitative measuring apparatus as defined in claim 58, wherein

the test strip fixing device or the fixing table is provided with an inclination part, and

the test strip fixing device and the fixing table are brought into contact at the inclination part, thereby fixing the test strip fixing device on the fixing table.

60. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device is integrated with the fixing table.

61. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device is provided with handles.

62. The chromatography quantitative measuring apparatus as defined in claim 54, wherein

the test strip fixing device is provided with a needle which penetrates the immuno-chromatography test strip.

63. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the carrier is provided with grooves, and

the fixing table or the measurement table is provided with a guide which can be inserted in the grooves.

64. The chromatography quantitative measuring apparatus as defined in claim 63, wherein

the grooves are formed by a laser cutter.

65. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is provided with an insertion slot in which the immuno-chromatography test strip can be inserted.

66. The chromatography quantitative measuring apparatus as defined in claim 65, wherein

the insertion slot is inclined.

67. The chromatography quantitative measuring apparatus as defined in claim 65, wherein

the immuno-chromatography test strip is provided with a notch at its end on the side of insertion into the fixing table, and

the fixing table is provided with a projection which has the shape same as that of the notch.

68. The chromatography quantitative measuring apparatus as defined in claim 67, wherein

the notch is provided asymmetrically with respect to the center line of the immuno-chromatography test strip in the longer-side direction.

69. The chromatography quantitative measuring apparatus as defined in claim 65, wherein

the carrier is provided with a groove at its end on the side of insertion of the immuno-chromatography test strip into the fixing table, and

the fixing table is provided with a projection which can be inserted in the groove.

70. The chromatography quantitative measuring apparatus as defined in claim 69, including:

a means for detecting whether the projection is inserted in the groove.

71. The chromatography quantitative measuring apparatus as defined in claim 65, wherein

the immuno-chromatography test strip is shaped to have stages by narrowing the width on the side of insertion into the fixing table.

72. The chromatography quantitative measuring apparatus as defined in claim 65, wherein

the fixing table is provided with an elastic member for pressing the immuno-chromatography test strip.

73. The chromatography quantitative measuring apparatus as defined in claim 72, wherein

the elastic member is integrated with the fixing table.

74. The chromatography quantitative measuring apparatus as defined in claim 72, wherein

the elastic member has its end inclined.

75. The chromatography quantitative measuring apparatus as defined in claim 72, including:

a mechanism for releasing the press by the elastic member.

76. The chromatography quantitative measuring apparatus as defined in claim 40, including:

an elastic member for pressing the immuno-chromatography test strip.

77. The chromatography quantitative measuring apparatus as defined in claim 72 or 76, wherein

the elastic member is detachable.

78. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

an operator can hold the carrier to detach the immuno-chromatography test strip from the fixing table.

79. The chromatography quantitative measuring apparatus as defined in claim 78, wherein

the carrier is bent to create a space between the fixing table and the end of the carrier.

80. The chromatography quantitative measuring apparatus as defined in claim 79, wherein

the carrier is provided with a groove to be bent therealong.

81. The chromatography quantitative measuring apparatus as defined in claim 78, wherein

the carrier protrudes above the fixing table.

82. The chromatography quantitative measuring apparatus as defined in claim 78, wherein

a part of the carrier is provided with a slip stopper.

83. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is provided with a groove for receiving the inspection target solution.

84. The chromatography quantitative measuring apparatus as defined in claim 83, wherein

the groove is given a slope, so that the inspection target solution can be supplied to the development layer from the direction of the cross section of the immuno-chromatography test strip.

85. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is subjected to water repellent finishing.

86. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table is attached with an absorbent material.

87. The chromatography quantitative measuring apparatus as defined in claim 40, wherein

the fixing table has a through hole in which a removal bar can be inserted, and

the bar is inserted in the through hole to press the immuno-chromatography test strip, thereby removing the immuno-chromatography test strip from the fixing table.

88. The chromatography quantitative measuring apparatus as defined in claim 87, wherein

the removal bas is integrated with the fixing table.