Devices for testing for the presence and/or concentration of an analyte in a body fluid

• US 20010039057A1
• Filed: 06/14/2001
• Published: 11/08/2001
• Est. Priority Date: 04/05/1996
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Wilson, James N., Douglas, Joel S., Drexler, Karen R.
• Granted Patent: US 6,818,180 B2
• Time in Patent Office: Days
• US Class Current: 436/169
• CPC Class Codes: G01N 33/521 Single-layer analytical elements
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: Y10S 435/805 Test papers

Abstract

Devices and methods for utilizing dry chemistry dye indicator systems for body fluid analysis such as glucose level in whole blood are provided by incorporating a porous membrane with a skin side which enables separation of whole blood and visually reading the indicator without removing the red blood cell portion of the blood from the membrane. The devices also enable visual reading of the indicator by use of a membrane or matrix which provides separation of whole blood in a lateral flow of the blood through the matrix from the input area to a test area of the matrix . The devices also provide for microtitration of fluid samples in fixed volumetric openings containing indicator reagent. Another aspect of the device provides a determination of hematocrit level in whole blood in combination with indicator indication of analyte concentration which can be compensated for the hematocrit level. The devices provided are low cost due to efficient manufacturing methods provided.

Claims

1. A method of testing blood for the presence or concentration of an analyte comprising:

providing a matrix member comprising a skin side and a test side wherein the skin side comprises a porous skin which is a water insoluble polymeric layer capable of blocking the passage of red blood cells and of allowing passage of blood fluids containing an analyte to the test side of the matrix and wherein the test side of the matrix is the opposite side from the skin side and is isotropic for uniform distribution therein of fluid received from the skin side and comprises an indicator capable of indicating the presence or concentration of the analyte;

applying a blood sample to the skin side of the matrix; and

reading or measuring on the test side of the matrix the indication provided by the indicator of the presence or concentration of the analyte without removal of the red blood cells from the skin side of the matrix.

2. A method according to

claim 1

wherein the reading or measurement is provided by an instrument.

3. A method according to

claim 1

wherein the reading or measurement is provided visually.

4. A method according to

claim 3

wherein the reading or measurement is made by comparison to a reference color chart.

5. A method according to

claim 1

wherein the matrix is of sufficient thickness and optical characteristic whereby the red blood cells retained on the skin side do not interfere with the reading or measurement at the surface of the test side of the matrix.

6. A device for testing blood for the presence or concentration of an analyte comprising:

a holder comprising an opening for receiving a blood sample;

and

a matrix member comprising a skin side and a test side wherein the skin is a water insoluble polymeric layer capable of blocking the passage of red blood cells and of allowing passage of blood fluids containing an analyte to the test side of the matrix and wherein the test side of the matrix is the opposite side from the skin side an is isotropic for uniform distribution therein of fluid received from the skin side;

wherein the matrix member is attached to the holder whereby the skin side is oriented toward the opening in the holder for receiving the blood sample such that when a blood sample is applied in said opening the blood contacts the skin side of the matrix allowing the blood fluids to pass to the test side of the matrix and red blood cells to be retained on the skin side of the matrix.

7. A device according to

claim 6

wherein the test side of the matrix comprises an indicator.

8. A device according to

claim 6

wherein the matrix member comprises a polyethersulfone polymer.

56. A kit for use by an individual comprising:

a test strip device according to

claim 6

;

an antiseptic applicator;

an anesthetic applicator;

a sharp article for puncturing the skin of the individual to provide a blood sample; and

a bandage for the skin puncture site.

9. A method of making a device for testing blood for the presence of an analyte comprising:

providing a holder comprising an opening for receiving a blood sample;

providing a matrix member comprising a skin side and a test side wherein the skin is a water insoluble polymeric layer capable of blocking passage of red blood cells and of allowing passage of blood fluids containing an analyte to the test side of the matrix and wherein the test side of the matrix is isotropic for uniform distribution therein of fluid received from the skin side; and

laminating the skin side of matrix member to the holder whereby the opening communicates with the skin on the skin side of the matrix.

10. A method according to

claim 9

comprising applying to the test side of the matrix an indicator capable of indicating the presence or concentration of an analyte.

11. A device for testing concentration of an analyte in a fluid sample comprising:

a first member comprising an opening having a predetermined volumetric size; and

a porous matrix member positioned within said opening in the first member wherein the matrix member comprises an indicator capable of indicating the presence of the analyte and wherein the matrix member comprises a skin side and a test side wherein the skin side is capable of blocking the passage of solids present in the fluid and of allowing passage of fluid containing an analyte to the test side of the matrix positioned within said opening to provide indication of the analyte on a volumetric basis.

12. A device according to

claim 11

comprising a support member comprising an opening therein on which support member the first member containing the matrix member is mounted such that the opening in the first member is at least in part aligned with the opening in the support member, whereby the device is capable of receiving a fluid through one opening and allowing detection of the indication of the indicator through the other opening.

13. A device according to

claim 11

wherein the first member is rigid in comparison to the matrix member and the matrix member positioned in the opening is a discrete shape and size substantially corresponding to the volumetric size of the opening in the first member.

14. A device according to

claim 12

wherein the first member is rigid in comparison to the matrix member and the matrix member is compressible and is larger than the opening in the first member whereby a portion of the matrix member is positioned within said opening and a portion of the matrix member is compressed between the first member and the support member.

15. A device according to

claim 14

wherein the skin side of the matrix member is positioned toward the first member and an adhesive is applied between the matrix member and the first member to provide a seal around each opening in the first member.

16. A device according to

claim 14

wherein the skin side of the matrix member is positioned toward the support member portion of the device and an adhesive is applied between the matrix member and the support member to provide a seal around each opening in the support member.

17. A device according to

claim 11

wherein the matrix member comprises a polyethersulfone polymer.

18. A device according to

claim 15

wherein the matrix member comprises a polyethersulfone polymer.

19. A device according to

claim 16

wherein the matrix member comprises a polyethersulfone polymer.

20. A device according to

claim 11

further comprising a plurality of openings in the first member, a matrix member positioned within each such opening and a plurality of openings in the support member positioned to correspond to the openings in the first member.

21. A device according to

claim 15

further comprising a plurality of openings in the first member, a matrix member positioned within each such opening and plurality openings in the support member positioned to correspond to the openings in the first member and comprising machine readable reference codes on the first member or the support member.

22. A device according to

claim 16

further comprising a plurality of openings in the first member, a matrix member positioned within each such opening and plurality openings in the support member positioned to correspond to the openings in the first member and comprising machine readable reference codes on the first member or the support member.

23. A device according to

claim 20

wherein the plurality of openings in the first member are interconnected with a capillary passageway and the first member is covered by a cover member having an opening for receiving the fluid sample wherein the opening in the cover member communicates with the capillary passageway thus enabling the fluid to flow from the opening in the cover through the capillary passageway into the interconnected openings in the first member.

40. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 11

;

applying a fluid to the device and allowing the fluid to permeate the matrix member within the opening in the first member and to fill the predetermined volume of the opening in the first member; and

reading or measuring the indication provided by the indicator to provide indication of the analyte on a volumetric basis.

41. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 12

;

applying a fluid to an opening on one side of the device and allowing the fluid to permeate the matrix member within the opening in the first member and to fill the predetermined volume of the opening in the first member; and

reading or measuring through the aligned opening on the other side of the device the indication provided by the indicator to provide indication of the analyte on a volumetric basis.

42. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 20

;

applying a fluid to an opening on one side of the device and allowing the fluid to permeate the matrix member within the opening in the first member and to fill the predetermined volume of the opening in the first member; and

reading or measuring through the aligned opening on the other side of the device the indication provided by the indicator to provide indication of the analyte on a volumetric basis.

58. A device according to

claim 23

comprising a wetting agent applied to the capillary passageway comprising dimethylsiloxane ethylene oxide, a hydrophilic printing ink or A BSI Photolink™

hydrophilic surface treatment.

59. A device according to

claim 23

wherein the member containing the capillary passageway is made of CYREX injection molded plastic.

24. A method of making a device for testing concentration of an analyte in a fluid comprising:

providing a first member being substantially noncompressible and having an opening therein of a predetermined volumetric size for receiving a fluid containing an analyte;

providing a porous matrix member which is fluid permeable and compressible; and

pressing the matrix member against the first member so that a portion of the matrix member protrudes within said opening and a portion of the matrix member is compressed against the surface of the first member adjacent to said opening.

25. A method according to

claim 24

further comprising:

providing a support member having an opening therein; and

laminating the support member to the first member before or after the matrix member is pressed against the first member such that a portion of the matrix member is compressed or the compressed portion of the matrix member is positioned between the support member and the first member and such that the opening in the support member and the opening in the first member are at least in part aligned.

26. A method according to

claim 24

comprising:

removing at least part of the portion of the matrix member compressed against the surface of the first member and leaving in the opening the portion of the matrix member which has protruded within said opening.

27. A method according to

claim 25

comprising providing a matrix member having a skin on one surface capable of blocking the passage of solids present in the fluid and of allowing passage of fluid containing an analyte into the matrix.

28. A method according to

claim 27

wherein the skin side of the matrix member is pressed against the first member and a portion of the skin protrudes within the opening in the first member.

29. A method according to

claim 27

wherein the skin side of the matrix is positioned away from the first member.

30. A method according to

claim 26

comprising providing a matrix member having a skin on one surface capable of blocking the passage of solids present in the fluid and of allowing passage of fluid containing an analyte into the matrix.

31. A method according to

claim 30

wherein the skin side of the matrix member is pressed against the first member and a portion of the skin protrudes within the opening in the first member.

32. A method according to

claim 31

wherein the skin side of the matrix is positioned away from the first member and is compressed against the surface of the support member.

33. A method according to

claim 24

comprising:

providing a skin film capable of blocking passage of solids present in the fluid and allowing passage of fluid containing an analyte; and

laminating the skin film on one surface of the matrix member before or after the matrix member is pressed against the first member.

34. A method according to

claim 25

comprising:

providing a skin film capable of blocking passage of solids present in the fluid and allowing passage of fluid containing an analyte; and

laminating the skin film on one surface of the matrix member before or after the matrix member is pressed against the first member.

35. A method according to

claim 25

wherein the first member is provided with a plurality of openings, the matrix member is pressed into each opening and the support member is provided with plural openings at least in part aligned with the openings in the first member.

36. A method according to

claim 27

wherein the first member is provided with a plurality of openings, the matrix member is pressed into each opening and the support member is provided with plural openings at least in part aligned with the openings in the first member.

37. A method according to

claim 28

wherein the first member is provided with a plurality of openings, the matrix member is pressed into each opening and the support member is provided with plural openings at least in part aligned with the openings in the first member.

38. A method according to

claim 35

wherein the plurality of openings in the first member are interconnected with a capillary passageway and the first member is covered by a cover member having an opening for receiving the fluid sample wherein the opening in the cover member communicates with the capillary passageway thus enabling the fluid to flow from the opening in the cover through the capillary passageway into the interconnected openings in the first member.

39. A method according to

claim 35

further comprising providing a color reference standard positioned on the device for visual comparison with the indication of the indicator viewed in each opening.

43. A device for the testing for the presence or concentration of an analyte in a fluid sample comprising:

a first member comprising an opening for receiving a fluid sample;

a porous matrix member positioned in communication with and extending laterally from said opening in the first member wherein the matrix member comprises an initial area which is in communication with the opening and a test area which is a given distance laterally from the initial area, wherein the matrix member contains pores which are capable of blocking in the lateral distance between the initial area and the test area the passage of solids in the fluid sample and are capable of allowing passage of fluid the lateral distance from the initial area to the test area, and wherein the test area of the matrix comprises an indicator capable of indicating the presence or concentration of the analyte.

44. A device according to

claim 43

further comprising a support member comprising an opening therein on which support member the first member and the matrix member are mounted such that the matrix member is positioned between the first member and the support member and such that the opening in the support member is offset from the opening in the first member and is positioned over at least a portion of the test area of the matrix whereby the device is capable of receiving a fluid through an opening at the initial area of the matrix, allowing the fluid to pass through the matrix from the initial area of the matrix to the test area of the matrix, the pores in the matrix blocking the passage of solids from the initial area of the matrix to the test area of the matrix, and allowing detection of the indication of the indicator through an opening in the support member at the test area of the matrix.

45. A device according to

claim 43

wherein the first member comprises a second opening positioned laterally from the initial area of the matrix to correspond to the test area of the matrix member whereby the indication of the indicator can be detected through the second opening.

46. A device according to

claim 45

further comprising a support member on which support member the first member and the matrix member are mounted such that the matrix member is positioned between the first member and the support member whereby the device is capable of receiving a fluid through one opening at the initial area of the matrix, allowing the fluid to pass through the matrix from the initial area of the matrix to the test area of the matrix, blocking the passage of solids from the initial area of the matrix to the test area of the matrix, and allowing detection of the indication of the indicator through the second opening in the first member.

47. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 43

;

applying a fluid to the opening for receiving a fluid sample and allowing the fluid to flow through the porous matrix member to the test area;

reading or measuring the indication provided by the indicator.

48. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 44

;

applying a fluid to the opening for receiving a fluid sample and allowing the fluid to flow through the porous matrix member to the test area;

reading or measuring the indication provided by the indicator.

49. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 45

;

applying a fluid to the opening for receiving a fluid sample and allowing the fluid to through the porous matrix member to the test area;

reading or measuring the indication provided by the indicator.

50. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 46

;

applying a fluid to the opening for receiving a fluid sample and allowing the fluid to through the porous matrix member to the test area;

reading or measuring the indication provided by the indicator.

51. A device for the testing of the presence or concentration of an analyte in a fluid sample comprising:

a member comprising a first opening for receiving a fluid sample and a second opening for receiving fluid from the first opening;

a restricted passageway communicating with the first opening and the second opening whereby the fluid sample can from the first opening to the second opening; and

a detector for detecting and measuring the rate of flow of the fluid sample through the restricted passageway.

52. A device according to

claim 51

comprising a porous matrix positioned in the second opening and comprising an indicator for indicating the presence or concentration of an analyte in the fluid sample.

53. A device according to

claim 52

wherein the porous matrix comprises a skin side positioned to receive the of fluid from the passageway and capable of blocking the passage of solids in the fluid and of allowing passage of fluids containing an analyte to enter the matrix for reaction with an indicator in the porous matrix.

54. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 51

;

applying a fluid to the first opening;

detecting and measuring the rate of initial of the fluid through the passageway; and

correlating the rate to known analyte concentration levels to indicate the analyte concentration in the fluid.

55. A method of testing a fluid for the concentration of an analyte present in the fluid comprising:

providing a device according to

claim 52

;

applying a fluid to the first opening;

detecting and measuring the rate of initial of the fluid through the passageway; and

correlating the flow rate to known analyte concentration levels to indicate the analyte concentration in the fluid; and

reading or measuring the indication provided by the indicator.

57. A method of initiating the reading and timing sequence of a meter reading a test strip containing an indicator dye system comprising sensing the input of the liquid sample into the test strip positioned in the meter.