Analyte concentration detection devices and methods

• US 20040191119A1
• Filed: 03/24/2003
• Published: 09/30/2004
• Est. Priority Date: 03/24/2003
• Status: Active Grant

• Current Assignee: Intuity Medical, Inc.
• Original Assignee: Sarnoff Corporation (SRI International, Inc.)
• Inventors: Desai, Nitin V., Varma, Bobby, Zanzucchi, Peter J., Ho, Wen, McBride, Sterling E.
• Granted Patent: US 7,052,652 B2
• Time in Patent Office: Days
• US Class Current: 422/504
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150755 Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
• CPC Class Codes: A61B 5/151 Devices specially adapted for taking samples of capillary blood, e.g. by lancets , needles or blades
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 21/78 producing a change of colour
• 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 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10T 436/144444 : Glucose

Abstract

Arrangements for the detection of the presence and/or concentration of an analyte in a sample of bodily fluid include diffuse transmission, diffuse reflection and edge or waveguide illumination arrangements. A vertical flow assay arrangement and/or technique is also disclosed, and includes a detection component that can be in the form of an array of optical detection elements. A number of assay pad constructions are described which may include at least one or more of the following components: a prefilter component, a reflective component, a membrane component, a reagent component, a mesh component, and a component to prevent lateral spreading.

Claims

1. A device for monitoring the concentration of an analyte present in bodily fluid, the device comprising a detector, the detector comprising a sensor, the sensor comprising a CMOS sensor, a CCD sensor, or a photodiode.

2. The device of claim 1, wherein the sensor comprises a CMOS sensor.

3. The device of claim 1, wherein the analyte comprises glucose.

4. The devices of claim 1, wherein the bodily fluid comprises whole blood.

5. The device of claim 1, wherein the device comprises an array formed from a plurality of the sensors.

6. The device of claim 5, wherein the device comprises a linear array of the sensors.

7. The device of claim 1, wherein the device further comprises a microneedle.

8. The device of claim 1, wherein the device is ambulatory.

9. The device of claim 1, further comprising a reaction chamber for receiving a sample of bodily fluid to be analyzed.

10. The device of claim 9, wherein the reaction chamber comprises a microchannel.

11. The device of claim 9, further comprising an assay pad located within the reaction chamber adapted to receive the sample to be analyzed.

12. The device of claim 9, further comprising a light source adapted to provide light incident upon the assay pad.

13. The device of claim 12, wherein the light source is arranged relative to the reaction chamber and the assay pad such that light transmitted from the light source is at least partially transmitted through the reaction chamber and the assay pad, the sensor is arranged in a manner such that the transmitted light is received by the sensor.

14. The device of claim 12, wherein the light source is arranged relative to the reaction chamber and assay pad such that light is transmitted from the light source and at least partially reflected off the assay pad, and the sensor is arranged relative to the reaction chamber and assay pad to receive light reflected off the assay pad.

15. The device of claim 12, further comprising a waveguide associated with the assay pad, the light source is arranged such that light emitted therefrom is incident upon that waveguide, the waveguide is arranged relative to the assay pad such that light transmitted therein from the light source illuminates the assay pad, the assay pad is constructed to at least partially reflect the light incident thereon, and the detector arranged to receive light reflected by the assay pad.

16. The device of claim 15, wherein the waveguide is arranged to illuminate a lateral edge of the assay pad, and the sensor is arranged to receive reflected light via the waveguide.

17. The device of claim 15, wherein the waveguide wherein at least one side of the waveguide is provided with an antireflective coating.

18. The device of claim 11, further comprising a lens disposed between the sensor and the assay pad.

19. The device of claim 18, wherein the lens is a refractive lens.

20. The device of claim 18, wherein the lens is a diffractive lens.

21. The device of claim 18, wherein the lens is integral with the sensor.

22. A device for conducting an assay to determine the concentration of an analyte in a sample of bodily fluid, the device comprising:

a sample collection channel having a bottom with at least one opening;

an assay pad in communication with at least one opening of the channel, the assay pad comprising a reagent adapted to produce a chemical reaction when exposed to the analyte, the chemical reaction producing a color change in the assay pad; and

a linear array of CMOS optical detectors disposed relative to the assay pad so as to detect the color change.

23. The device of claim 22, wherein the device is ambulatory.

24. The device of claim 23, wherein the device further comprises a skin penetration member for extracting the sample of bodily fluid from the wearer.

25. The device of claim 22, wherein the analyte is glucose and the bodily fluid is whole blood.

26. The device of claim 22, wherein the channel has a general shape of an elongated upside-down U when disposed in its operable position within the device.

27. The device of claim 22, wherein the channel defines a volume which is no greater than 250 nanoliters.

28. The device of claim 22, wherein the channel defines a length, and the linear array has a plurality of CMOS sensors that define a length of the array that is commensurate to the length of the channel.

29. The device of claim 22, wherein the assay pad comprises:

a first component constructed to separate red blood cells from plasma and further comprising a diffuse reflective material;

a second component comprising the chemical reagent; and

a third component comprising a polyamide-containing mesh.

30. The device of claim 29, wherein the diffuse reflective material comprises zirconium oxide.

31. The device of claim 29, wherein the second layer comprises a membrane spin-coated with the chemical reagent.

32. The device of claim 29, wherein the second and third layers are integrated by incorporating the chemical reagent into the polyamide-containing membrane.

33. An assay pad construction comprising:

a first component comprising a constituent to separate red blood cells from plasma and further comprising a diffuse reflective material constituent;

a second component comprising a chemical reagent; and

a third component comprising a polyamide-containing mesh.

34. The pad of claim 33, wherein the diffuse reflective material comprises zirconium oxide.

35. The pad of claim 33, wherein the first component comprises a non-woven membrane coated with the diffuse reflective constituent.

36. The pad of claim 33, wherein the second component is coated onto the third component.

37. The pad of claim 36, wherein the second component is entirely subsumed by, or retained within, the third component.

38. The pad of claim 36, wherein the second component is at least partially subsumed by, or retained within, the third component, and forms a film on a surface of the third component.

39. The pad of claim 35, wherein the diffuse reflective constituent is entire by, subsumed by, or retained within, the membrane.

40. The pad of claim 35, wherein the diffuse reflective constituent is at least partially subsumed by, or retained within, the membrane and forms a film on a surface of the membrane.

41. The part of claim 33, wherein the first component comprises a hydrophilic filter material.

42. The pad of claim 41, wherein the filter material comprises polyvinyl fluoride or polyacrylic acid.

43. The pad of claim 42, wherein the filter material is coated with a mixture containing zirconium oxide and a polymer binder.

44. The pad of claim 43, wherein the coated mixture forms a film on top of the filter material, the film having a thickness no greater than 5 μ

m.

45. The pad of claim 41, wherein the third component comprises a woven mesh having mesh openings on the order of 68 micros and filaments with a diameter on the order of 50 microns.

46. The pad of claim 43, wherein the polymer binder is a permeable polymer binder.

47. The pad of claim 46, wherein the binder comprises HPMC or vinyl butryl.

48. The pad of claim 33, wherein the second component further comprises a binder material.

49. The pad of claim 48, wherein the binder comprises HPMC or PAA.

50. An assay pad comprising:

a first component comprising a diffuse reflective material;

a second component comprising a permeable hydrophobic material;

a third component comprising a reagent; and

a fourth component comprising a mesh or a membrane.

51. The pad of claim 50, wherein the first component further comprises a permeable hydrophobic binder.

52. The pad of claim 51, wherein the binder comprises HPMC or an acrylic resin.

53. The pad of claim 50, wherein the second component comprises a film of polyacrylic acid.

54. The pad of claim 50, wherein the third component further comprises a binder.

55. The pad of claim 50, wherein the fourth component comprises a mesh or a membrane constructed at least in part from polyvinyl fluoride.

56. The pad of claim 50, wherein the third component is entirely subsumed by, or retained within, the fourth component.

57. A method of performing an assay to determine the concentration of an analyte in a sample of bodily fluid, the method comprising:

(i) providing a sample collection channel having a first volume;

(ii) introducing a sample of bodily fluid into the channel, the sample introduced into the channel having a second volume which is less than the first volume;

(iii) vertically conveying the sample from the channel onto an assay pad;

(iv) reacting the analyte in the sample with a chemical reagent in the assay pad thereby producing a color change in the assay pad; and

(v) detecting the color change with a linear array of CMOS sensors by detecting the color change with each individual CMOS sensor in the array which is incident upon the area of color change in the assay pad.

58. A method of determining an estimated volume of a sample of bodily fluid being subjected to an assay, the method comprising:

(i) providing an elongated sample collection channel having a volume directly proportional to its length;

(ii) introducing a sample of bodily fluid into the channel;

(iii) vertically conveying the sample from the channel onto an assay pad;

(iv) reacting the analyte in the sample with a chemical reagent in the assay pad thereby producing a color change in the assay pad;

(v) disposing a linear array of CMOS sensors incident to the assay pad for detecting the color change, the length of the CMOS array being commensurate with the length of the collection channel;

(vi) detecting the color change with each individual CMOS sensor in the array which is incident upon the area of color change in the assay pad; and

(vii) calculating the estimated volume of the sample in the collection chamber based upon the number of sensors in the linear array which detect the change in color.