Blood testing unit and blood testing method and apparatus

• US 20030186457A1
• Filed: 03/28/2003
• Published: 10/02/2003
• Est. Priority Date: 03/28/2002
• Status: Active Grant

• Current Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Original Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Inventors: Tanaka, Hideaki, Nakamura, Kentarou, Iwaki, Yoshihide, Sakaino, Yoshiki, Terashima, Kaoru, Toya, Ichizou
• Granted Patent: US 7,282,179 B2
• Time in Patent Office: Days
• US Class Current: 436/169
• CPC Class Codes: B01L 2200/082 Handling hazardous material
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/047 Additional chamber, reservoir
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/5082 Test tubes per se
• CPC Class Codes: B01L 3/50825 Closing or opening means, corks, bungs closures for containers B65D; means for removing stoppers B67B7/02
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence

Abstract

A blood testing unit comprises a closed vessel having a blood introducing section formed at a certain area of the closed vessel. A blood constituent separating section is located within the closed vessel to separate plasma and/or serum from the blood sample introduced through the blood introducing section into the closed vessel. A reagent layer is located within the closed vessel, such that the reagent layer can be seen from the exterior. The reagent layer comprises a region for spreading the plasma and/or the serum, which has been separated by the blood constituent separating section from the blood sample, and a reagent supporte donor in the spreading region, the reagent undergoing a reaction with the plasma and/or the serum and forming a color as a result of the reaction.

Claims

1. A blood testing unit, comprising:

i) a closed vessel provided with a blood introducing section, which is formed at a certain area of the closed vessel and through which a blood sample is capable of being introduced into the closed vessel,

ii) a blood constituent separating section, which is located within the closed vessel and separates blood plasma and/or blood serum from the blood sample having been introduced through the blood introducing section into the closed vessel, and

iii) a reagent layer, which is located within the closed vessel, such that the reagent layer is capable of being seen from the exterior, the reagent layer comprising a region for spreading the blood plasma and/or the blood serum, which has been separated by the blood constituent separating section from the blood sample, and a reagent, which is supported on or in the region for spreading the blood plasma and/or the blood serum, the reagent being capable of undergoing a reaction with the blood plasma and/or the blood serum and forming a color as a result of the reaction.

2. A blood testing unit as defined in claim 1 wherein the closed vessel has a structure such that the area of the closed vessel other than the blood introducing section is constituted so as to keep the interior of the closed vessel in a water-tight state with respect to the exterior, and such that at least a certain area of the closed vessel is formed as a transparent area, and

the reagent layer is located such that the reagent layer is capable of being seen through the transparent area of the closed vessel from the exterior.

3. A blood testing unit as defined in claim 1 wherein the closed vessel comprises an outer vessel body, which has a bottom wall, and an inner vessel body, which has a bottom wall, and

the outer vessel body and the inner vessel body are combined with each other, such that the outer vessel body and the inner vessel body are capable of sliding with respect to each other, while a space defined by the outer vessel body and the inner vessel body is being kept in an approximately hermetically sealed state, the outer vessel body and the inner vessel body thus defining an enclosed space at the interior in a manner such that a pressure in the enclosed space is capable of being reduced.

4. A blood testing unit as defined in claim 3 wherein the blood introducing section is formed at the bottom wall of either one of the outer vessel body and the inner vessel body.

5. A blood testing unit as defined in claim 4 wherein the blood introducing section is formed at the bottom wall of the outer vessel body, and

the bottom wall of the inner vessel body is formed at an end area of the inner vessel body, which end area is remote from the bottom wall of the outer vessel body.

6. A blood testing unit as defined in claim 4 wherein a blood constituent separating membrane, which acts as the blood constituent separating section, is secured to the one vessel body having the bottomwall at which the blood introducing section is formed, such that the blood constituent separating membrane stands facing the bottom wall of the one vessel body.

7. A blood testing unit as defined in claim 6 wherein the reagent layer is located such that the reagent layer is in contact with a surface of the blood constituent separating membrane, which surface is opposite to the surface that stands facing the blood introducing section.

8. A blood testing unit as defined in claim 6 wherein the reagent layer is fitted to the other vessel body that is other than the one vessel body to which the blood constituent separating membrane is secured, such that the reagent layer is capable of being brought into contact with the blood constituent separating membrane.

9. A blood testing unit as defined in claim 8 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer, is a membrane-shaped region, which is located approximately in parallel with the blood constituent separating membrane.

10. A blood testing unit as defined in claim 8 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer, is a rod-shaped or plate-shaped region, which extends along an axial direction of the outer vessel body and the inner vessel body and is located such that an end area of the rod-shaped or plate-shaped region is capable of being brought into contact with the blood constituent separating membrane.

11. A blood testing unit as defined in claim 3 wherein the blood constituent separating section is secured tightly to an inner peripheral surface of either one of the outer vessel body and the inner vessel body, to which one vessel body the blood constituent separating section is secured, without any gap being formed between the blood constituent separating section and the inner peripheral surface of the one vessel body over an entire perimeter of the blood constituent separating section.

12. A blood testing unit as defined in claim 3 wherein at least either one of the outer vessel body and the inner vessel body is provided with a hole, through which air is capable of being introduced from the exterior to the interior of the one vessel body, and

the one vessel body is provided with a sealing member for closing the hole.

13. A blood testing unit as defined in claim 12 wherein the sealing member is a sheet-shaped member, which is adhered to the one vessel body.

14. A blood testing unit as defined in claim 3 wherein an O-ring is fitted onto an outer peripheral wall of the inner vessel body, the O-ring being capable of keeping the space, which is defined by the outer vessel body and the inner vessel body, in an approximately hermetically sealed state, and

the outer vessel body and the inner vessel body are capable of sliding with respect to each other, while the O-ring fitted onto the outer peripheral wall of the inner vessel body is being in contact with an inner peripheral wall of the outer vessel body.

15. A blood testing unit as defined in claim 3 wherein an outer peripheral wall of the inner vessel body is provided with an engagement section, which projects outwardly from outer peripheral wall of the inner vessel body,

an inner peripheral wall of the outer vessel body is provided with an engagement section, which projects inwardly from the inner peripheral wall of the outer vessel body, and the engagement section of the inner vessel body and

the engagement section of the outer vessel body are capable of engaging with each other in order to prevent the inner vessel body and the outer vessel body from separating from each other.

16. A blood testing unit as defined in claim 3 wherein the outer vessel body and the inner vessel body are provided with locking means for keeping the states of the outer vessel body and the inner vessel body when at least either one of the outer vessel body and the inner vessel body has been moved with respect to the other in a direction which increases a volume of the enclosed space defined at the interior by the outer vessel body and the inner vessel body, and the pressure in the enclosed space has thus been set at a negative pressure.

17. A blood testing unit as defined in claim 1 wherein the closed vessel is a bag-shaped vessel made from a flexible sheet material, and

a permeation member is accommodated within the bag-shaped vessel, the permeation member allowing the blood sample, which has been introduced through the blood introducing section into the bag-shaped vessel, to permeate through the permeation member toward the blood constituent separating section, and allowing the blood plasma and/or the blood serum, which has been separated by the blood constituent separating section from the blood sample, to permeate through the permeation member toward the reagent layer.

18. A blood testing unit as defined in claim 17 wherein a frame member is located so as to surround an outer periphery of the bag-shaped vessel, the frame member being adapted to draw and send the blood plasma and/or the blood serum, which has permeated through the permeation member, toward the reagent layer.

19. A blood testing unit as defined in claim 1 wherein the closed vessel is constituted of a plate-shaped member, and

a fine path is formed within the plate-shaped member, the fine path causing the blood sample, which has been introduced through the blood introducing section into the plate-shaped member, to move by capillary action through the fine path toward the blood constituent separating section, and causing the blood plasma and/or the blood serum, which has been separated by the blood constituent separating section from the blood sample, to move by capillary action through the fine path toward the reagent layer.

20. A blood testing unit as defined in claim 1 wherein the blood introducing section is constituted of a high-elasticity member capable of acting such that the high-elasticity member ordinarily closes the closed vessel, and such that, when a blood sampling needle is stuck into the high-elasticity member, the high-elasticity member allows a tip of the blood sampling needle to penetrate through the high-elasticity member into the closed vessel, while a region between an outer peripheral wall of the blood sampling needle and the high-elasticity member is being kept in an approximately hermetically sealed state.

21. A blood testing unit as defined in claim 20 wherein the high-elasticity member is made from rubber.

22. A blood testing unit as defined in claim 1 wherein a plurality of different kinds of reagents are supported at different positions on the reagent layer.

23. A blood testing unit as defined in claim 1 wherein the blood constituent separating section is constituted of a porous structure material, which allows the blood plasma and/or the blood serum to pass therethrough and obstructs solid constituents from passing therethrough.

24. A blood testing unit as defined in claim 23 wherein the porous structure material consists of a polysulfone membrane.

25. A blood testing unit as defined in claim 24 wherein the polysulfone membrane has a pore diameter falling within the range of 0.5 μ

m to 50 μ

m.

26. A blood testing unit as defined in claim 1 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer, contains a substance capable of generating heat in the presence of water.

27. A blood testing unit as defined in claim 1 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer, is provided with a mark representing information concerning the blood testing unit.

28. A blood testing unit as defined in claim 1 wherein an area of the reagent layer, which area is free from the reagent, is formed as a black plane, a plane of a color close to black, or a mirror plane.

29. A blood testing method, in which a blood test is performed by use of a blood testing unit as defined in claim 1, the method comprising the steps of:

i) irradiating measuring light to a reagent area of the reagent layer, which reagent area has formed the color as a result of the reaction with the blood plasma and/or the blood serum,

ii) detecting an intensity of the light having been reflected from the reagent area, and

iii) detecting an optical density of the reagent area in accordance with the thus detected intensity of the light having been reflected from the reagent area.

30. A blood testing method as defined in claim 29 wherein the measuring light is irradiated to the reagent area of the reagent layer of the blood testing unit, which reagent area has formed the color as a result of the reaction with the blood plasma and/or the blood serum, and to a mark area, which is provided with a mark representing information concerning the blood testing unit,

the intensity of the light, which has been reflected from the reagent area, and the intensity of the light, which has been reflected from the mark area, are detected,

the optical density of the reagent area is detected in accordance with the thus detected intensity of the light, which has been reflected from the reagent area, and

the information represented by the mark is read out in accordance with the thus detected intensity of the light, which has been reflected from the mark area.

31. A blood testing method as defined in claim 30 wherein a common photodetector is utilized for both the detection of the optical density of the reagent area and the readout of the information represented by the mark.

32. A blood testing method as defined in claim 30 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer of the blood testing unit, is provided with the mark representing the information concerning the blood testing unit, and

the detection of the optical density of the reagent area and the readout of the information represented by the mark are performed simultaneously.

33. A blood testing method as defined in claim 30 wherein a dummy testing unit, which is provided with the mark representing the information concerning the blood testing unit, is located at a predetermined position, at which the blood testing unit is to be located, and

the detection of the optical density of the reagent area from the blood testing unit and the readout of the information, which is represented by the mark, from the dummy testing unit are performed one after the other at a certain time interval.

34. A blood testing method as defined in claim 29 wherein the irradiation of the measuring light to the reagent area of the reagent layer and the detection of the intensity of the light having been reflected from the reagent area are performed from the side of one surface of the reagent layer opposite to the other surface of the reagent layer, on which other surface the blood plasma and/or the blood serum has been supplied to the reagent area.

35. A blood testing method as defined in claim 29 wherein a plurality of independent light intensity detecting operations are performed with respect to a plurality of subareas of the reagent area of the reagent layer, each of the independent light intensity detecting operations being performed for one of the plurality of the subareas of the reagent area,

results of the plurality of the independent light intensity detecting operations performed with respect to the plurality of the subareas of the reagent area are subjected to statistical processing, a light intensity value representative of the reagent area being obtained from the statistical processing, and

the thus obtained light intensity value representative of the reagent area is taken as the intensity of the light having been reflected from the reagent area.

36. A blood testing method, in which a blood test is performed by use of a blood testing unit as defined in claim 22, the method comprising the steps of:

i) irradiating measuring light to each of reagent areas of the reagent layer, each of which reagent areas has formed the color as a result of the reaction with the blood plasma and/or the blood serum, the measuring light having a wavelength adapted to the reagent contained in each of the reagent areas,

ii) detecting an intensity of the light having been reflected from each of the reagent areas, the detection of the intensity of the reflected light being performed with respect to each of the reagent areas, and

iii) detecting an optical density of each of the reagent areas in accordance with the thus detected intensity of the light having been reflected from each of the reagent areas.

37. A blood testing method as defined in claim 36 wherein the measuring light irradiated to each of the reagent areas of the reagent layer is a light component, which has been obtained through light separation so as to have the wavelength corresponding to the reagent contained in each of the reagent areas.

38. A blood testing method as defined in claim 36 wherein light, which contains the measuring light having the wavelength corresponding to the reagent contained in each of the reagent areas, is irradiated to each of the reagent areas of the reagent layer, and

the light having been reflected from each of the reagent areas is detected through light separation into light components, the light separation being performed with respect to each of the reagent areas.

39. A blood testing method as defined in claim 36 wherein a plurality of independent measuring light irradiating operations are performed with respect to the blood testing unit, each of the independent measuring light irradiating operations being performed for one of the plurality of the reagent areas of the blood testing unit.

40. A blood testing method as defined in claim 36 wherein the intensity of the light having been reflected from each of the reagent areas is detected with a photodetector, which has been divided into pixels, and with respect to each of the reagent areas.

41. A blood testing method as defined in claim 40 wherein the light having been reflected from each of the reagent areas is collected by at least one lens, which is located so as to have a correspondence relationship with each of the reagent areas, and

the thus collected light is guided to the photodetector, which has been divided into the pixels.

42. A blood testing method as defined in claim 36 wherein the irradiation of the measuring light to each of the reagent areas of the reagent layer and the detection of the intensity of the light having been reflected from each of the reagent areas are performed from the side of one surface of the reagent layer opposite to the other surface of the reagent layer, on which other surface the blood plasma and/or the blood serum has been supplied to the reagent areas.

43. A blood testing method as defined in claim 36 wherein a plurality of independent light intensity detecting operations are performed with respect to a plurality of subareas of each of the reagent areas of the reagent layer, each of the independent light intensity detecting operations being performed for one of the plurality of the subareas of each of the reagent areas,

results of the plurality of the independent light intensity detecting operations performed with respect to the plurality of the subareas of each of the reagent areas are subjected to statistical processing, a light intensity value representative of each of the reagent areas being obtained from the statistical processing, and

the thus obtained light intensity value representative of each of the reagent areas is taken as the intensity of the light having been reflected from each of the reagent areas.

44. A blood testing apparatus, in which a blood test is performed by use of a blood testing unit as defined in claim 1, the apparatus comprising:

i) means for irradiating measuring light to a reagent area of the reagent layer, which reagent area has formed the color as a result of the reaction with the blood plasma and/or the blood serum,

ii) means for detecting an intensity of the light having been reflected from the reagent area, and iii)

iii) means for detecting an optical density of the reagent area in accordance with the thus detected intensity of the light having been reflected from the reagent area.

45. A blood testing apparatus as defined in claim 44 wherein the measuring light is irradiated to the reagent area of the reagent layer of the blood testing unit, which reagent area has formed the color as a result of the reaction with the blood plasma and/or the blood serum, and to a mark area, which is provided with a mark representing information concerning the blood testing unit,

the intensity of the light, which has been reflected from the reagent area, and the intensity of the light, which has been reflected from the mark area, are detected,

the optical density of the reagent area is detected in accordance with the thus detected intensity of the light, which has been reflected from the reagent area, and

the information represented by the mark is read out in accordance with the thus detected intensity of the light, which has been reflected from the mark area.

46. A blood testing apparatus as defined in claim 45 wherein a common photodetector is utilized for both the detection of the optical density of the reagent area and the readout of the information represented by the mark.

47. A blood testing apparatus as defined in claim 45 wherein the region for spreading the blood plasma and/or the blood serum, which region constitutes the reagent layer of the blood testing unit, is provided with the mark representing the information concerning the blood testing unit, and

the detection of the optical density of the reagent area and the readout of the information represented by the mark are performed simultaneously.

48. A blood testing apparatus as defined in claim 45 wherein a dummy testing unit, which is provided with the mark representing the information concerning the blood testing unit, is located at a predetermined position, at which the blood testing unit is to be located, and

the detection of the optical density of the reagent area from the blood testing unit and the readout of the information, which is represented by the mark, from the dummy testing unit are performed one after the other at a certain time interval.

49. A blood testing apparatus as defined in claim 44 wherein the irradiation of the measuring light to the reagent area of the reagent layer and the detection of the intensity of the light having been reflected from the reagent area are performed from the side of one surface of the reagent layer opposite to the other surface of the reagent layer, on which other surface the blood plasma and/or the blood serum has been supplied to the reagent area.

50. A blood testing apparatus as defined in claim 44 wherein a plurality of independent light intensity detecting operations are performed with respect to a plurality of subareas of the reagent area of the reagent layer, each of the independent light intensity detecting operations being performed for one of the plurality of the subareas of the reagent area,

results of the plurality of the independent light intensity detecting operations performed with respect to the plurality of the subareas of the reagent area are subjected to statistical processing, a light intensity value representative of the reagent area being obtained from the statistical processing, and

the thus obtained light intensity value representative of the reagent area is taken as the intensity of the light having been reflected from the reagent area.

51. A blood testing apparatus, in which a blood test is performed by use of a blood testing unit as defined in claim 22, the apparatus comprising:

i) means for irradiating measuring light to each of reagent areas of the reagent layer, each of which reagent areas has formed the color as a result of the reaction with the blood plasma and/or the blood serum, the measuring light having a wavelength adapted to the reagent contained in each of the reagent areas,

ii) means for detecting an intensity of the light having been reflected from each of the reagent areas, the detection of the intensity of the reflected light being performed with respect to each of the reagent areas, and

iii) means for detecting an optical density of each of the reagent areas in accordance with the thus detected intensity of the light having been reflected from each of the reagent areas.

52. A blood testing apparatus as defined in claim 51 wherein the measuring light irradiated to each of the reagent areas of the reagent layer is a light component, which has been obtained through light separation so as to have the wavelength corresponding to the reagent contained in each of the reagent areas.

53. A blood testing apparatus as defined in claim 51 wherein light, which contains the measuring light having the wavelength corresponding to the reagent contained in each of the reagent areas, is irradiated to each of the reagent areas of the reagent layer, and

the light having been reflected from each of the reagent areas is detected through light separation into light components, the light separation being performed with respect to each of the reagent areas.

54. A blood testing apparatus as defined in claim 51 wherein a plurality of independent measuring light irradiating operations are performed with respect to the blood testing unit, each of the independent measuring light irradiating operations being performed for one of the plurality of the reagent areas of the blood testing unit.

55. A blood testing apparatus as defined in claim 51 wherein the intensity of the light having been reflected from each of the reagent areas is detected with a photodetector, which has been divided into pixels, and with respect to each of the reagent areas.

56. A blood testing apparatus as defined in claim 55 wherein the light having been reflected from each of the reagent areas is collected by at least one lens, which is located so as to have a correspondence relationship with each of the reagent areas, and

the thus collected light is guided to the photodetector, which has been divided into the pixels.

57. A blood testing apparatus as defined in claim 51 wherein the irradiation of the measuring light to each of the reagent areas of the reagent layer and the detection of the intensity of the light having been reflected from each of the reagent areas are performed from the side of one surface of the reagent layer opposite to the other surface of the reagent layer, on which other surface the blood plasma and/or the blood serum has been supplied to the reagent areas.

58. A blood testing apparatus as defined in claim 51 wherein a plurality of independent light intensity detecting operations are performed with respect to a plurality of subareas of each of the reagent areas of the reagent layer, each of the independent light intensity detecting operations being performed for one of the plurality of the subareas of each of the reagent areas,

results of the plurality of the independent light intensity detecting operations performed with respect to the plurality of the subareas of each of the reagent areas are subjected to statistical processing, a light intensity value representative of each of the reagent areas being obtained from the statistical processing, and

the thus obtained light intensity value representative of each of the reagent areas is taken as the intensity of the light having been reflected from each of the reagent areas.