ANALYTE SENSOR WITH EXTENDED RANGE OF DETECTION

• US 20130172699A1
• Filed: 12/29/2012
• Published: 07/04/2013
• Est. Priority Date: 12/29/2011
• Status: Active Grant

• Current Assignee: Optica, Inc.
• Original Assignee: Wellsense, Inc.
• Inventors: Rebec, Mihailo V.
• Granted Patent: US 9,649,056 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 2560/0233 Optical standards
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence

Abstract

Embodiments provide sensors, such as implantable sensors, and methods of producing such sensors. An implantable sensor may include a base, one or more chambers, and one or more sensor reagents. A membrane may be coupled to the chambers over the sensor reagents. The implantable sensor may be at least partially implanted into the dermis of an animal. One or more of the sensor reagents may emit light or exhibit a color change in response to the presence of a target analyte or reaction product thereof. The response may be detected and analyzed by the user or by a reader device to determine the target analyte concentration.

Claims

1. An analyte sensor, comprising:

a base having an upper surface and an opposite lower surface, a first end, and an opposite second end; and

a first and a second analysis region coupled to the base, the first analysis region comprising a first analyte reagent system and the second analysis region comprising a second analyte reagent system,

wherein the first and the second analysis regions have contiguous first and second detection ranges, respectively, for a target analyte, and substantially coextensive ranges of response, the first and second analysis regions configured to exhibit different responses within said coextensive ranges upon exposure to a given concentration of the target analyte.

2. The analyte sensor of claim 1, further comprising one or more membranes coupled to the base, the one or more membranes being permeable to a target analyte.

3. The analyte sensor of claim 2, wherein the one or more membranes includes a first membrane portion and a second membrane portion, wherein the permeability of the first membrane portion to the target analyte is greater than the permeability of the second membrane portion to the target analyte.

4. The analyte sensor of claim 1, the base defining first and second chambers therein, the first analyte reagent system disposed in the first chamber and the second analyte reagent system disposed in the second chamber.

5. The analyte sensor of claim 1, the base defining a first chamber therein, the first and second analyte reagent systems disposed in the first chamber.

6. The analyte sensor of claim 1, wherein the first and second analyte reagent systems are configured to exhibit corresponding first and second colors upon exposure to the given concentration of the analyte, said first and second colors being different colors.

7. The analyte sensor of claim 6, wherein at least one of the first and second colors is a color in the infrared range.

8. The analyte sensor of claim 1, wherein the first analyte reagent system and the second analyte reagent system have different chemical compositions.

9. The analyte sensor of claim 1, wherein the analyte sensor has a total thickness of 30-90 μ

m.

10. The analyte sensor of claim 1, wherein the analyte sensor has total thickness of 10 um-1 mm.

11. The analyte sensor of claim 1, wherein the analyte sensor has a total thickness of 50 μ

m or less.

12. The analyte sensor of claim 1, wherein the analyte sensor is configured to be retained in the body of a subject for at least one minute.

13. The analyte sensor of claim 1, wherein the analyte sensor is configured to be retained within the dermis of a subject for at least one month.

14. The analyte sensor of claim 1, wherein the base comprises a polymer material and TiO2.

15. The analyte sensor of claim 14, wherein the polymer material comprises a polyimide.

16. The analyte sensor of claim 1, wherein each of the first and the second analyte reagent systems includes at least one detection reagent and at least one indicator.

17. The analyte sensor of claim 16, further including a plurality of beads coupled to the base, wherein one or more of the detection reagent and the indicator are immobilized on the beads.

18. The analyte sensor of claim 17, the base defining one or more chambers therein, wherein one or more reagents of the first reagent system are deposited onto a first group of the beads and one or more reagents of the second reagent system are deposited onto a second group of the beads, and the beads are positioned within the one or more chambers.

19. The analyte sensor of claim 18, wherein the first and second groups of beads are disposed within one of said chambers.

20. The analyte sensor of claim 16, wherein the detection reagent is configured to interact with the target analyte to cause a change in pH, and the indicator includes a pH sensitive dye configured to produce a color change in response to the change in pH.

21. The analyte sensor of claim 16, wherein the indicator includes two or more of a lipophilic anion, a chromoionophore, and an ionophore, and the detection reagent includes an enzyme.

22. The analyte sensor of claim 13, wherein a first portion of the analyte sensor is configured to be retained within the dermis of a subject and a second portion of the analyte sensor is configured to be retained externally or within the epidermis of the subject.

23. The analyte sensor of claim 1, wherein the base comprises a reflective material.

24. The analyte sensor of claim 16, wherein the detection reagent comprises glucose oxidase.

25. The analyte sensor of claim 1, wherein the analyte sensor further comprises a first component coupled to at least the first and second analysis regions, the first component configured to provide a first gradient between the first and second analysis regions.

26. The analyte sensor of claim 25, wherein the first component is a membrane or gel layer and the first gradient is a permeability gradient resulting from variations in pore size, thickness, hydrophobicity, or reagent content of the first component.

27. The analyte sensor of claim 25, wherein the analyte sensor further comprises a second component coupled to at least the first and second analysis regions, the second component configured to provide a second gradient that extends transverse to the first gradient.

28. The analyte sensor of claim 27, wherein the second component is a membrane or gel layer and the second gradient is a result of variations in pore size, thickness, hydrophobicity, or reagent content of the second component.

29. The analyte sensor of claim 27, wherein the analyte sensor has a second permeability gradient that extends transverse to the first permeability gradient, the second permeability gradient formed by variations in reagent content or buffering systems among the first and second analyte reagent systems.

30. The analyte sensor of claim 1, the analyte sensor further comprising a third analysis region, the first, second, and third analysis regions having substantially coextensive ranges of response.

31. The analyte sensor of claim 30, wherein the third analysis region has a third detection range that overlaps the second detection range, the third analysis region configured to detect the target analyte.

32. The analyte sensor of claim 30, wherein the third analysis region is configured to detect a second analyte.

33. An analyte detection system for monitoring the concentration of a target analyte in the dermis of a subject, the system comprising:

an implantable analyte sensor with a first analysis region and a second analysis region, the first and second analysis regions having contiguous first and second detection ranges for a target analyte, respectively, and substantially coextensive ranges of response; and

a reader device having an optical sensor, a processor, and a non-volatile computer-readable storage medium endowed with instructions operable, upon execution by the processor, to cause the reader device to

capture an image of the analyte sensor within the dermis of the subject, and

calculate the concentration of the target analyte based at least on the captured image.

34. The system of claim 33, wherein the reader device is configured to calculate the concentration of the target analyte based at least on image data corresponding to the first and second analysis regions.

35. The system of claim 34, wherein the reader device is a mobile electronic device selected from the group consisting of a laptop, a tablet PC, or a mobile phone.

36. The system of claim 33, wherein the first and second analysis regions are configured to exhibit corresponding first and second colors at a given target analyte concentration, the first and second colors being different colors within said ranges of response.

37. The system of claim 36, wherein the contiguous detection ranges overlap, and the given target analyte concentration is a concentration within both of said contiguous detection ranges.

38. The system of claim 33, wherein the target analyte is glucose.

39. The system of claim 33, the analyte sensor having one or more control regions configured for use to calibrate a reader device or to correct a representative value.

40. The system of claim 33, the analyte sensor having one or more orientation marks configured for use by the reader device to orient a captured image of the analyte sensor.

41. The system of claim 33, wherein the analyte sensor further comprises a first component coupled to at least the first and second analysis regions, the first component configured to provide a first response gradient between the first and second analysis regions.

42. The system of claim 41, wherein the first component is a membrane or gel layer and the first response gradient is a permeability gradient resulting from variations in pore size, thickness, hydrophobicity, or reagent content of the first component.

43. The system of claim 41, wherein the analyte sensor further comprises a second component coupled to at least the first and second analysis regions, the second component configured to provide a second response gradient that extends transverse to the first response gradient.

44. The system of claim 43, wherein the second component is a membrane or gel layer and the second response gradient is a permeability gradient resulting from variations in pore size, thickness, hydrophobicity, or reagent content of the first component.

45. The system of claim 43, wherein the second response gradient is a response gradient resulting from variations in types or concentrations of analyte detection reagents, buffer components, or reagent combinations among analysis regions.

46. The system of claim 34, wherein the reader device is configured to determine the first and second detection ranges based at least on a pre-determined pattern stored or accessed by the reader device.

47. The system of claim 33, wherein the analyte sensor comprises a third analysis region, the third analysis region being substantially a duplicate of the first or second analysis region.

48. The system of claim 34, wherein the reader device is further configured to select at least one other region of the image for analysis.

49. The system of claim 48, wherein the reader device is further configured to determine, based at least on analysis of the at least one other region, that the analyte sensor is leaking or malfunctioning, determine a time frame for replacement of the analyte sensor, or correct the determined target analyte concentration.

50. A reader device for use with an analyte sensor implanted into the dermis of a subject, wherein the analyte sensor includes a plurality of analysis regions with contiguous detection ranges for a target analyte and coextensive ranges of response, the reader device comprising:

an optical sensor;

a processor; and

a non-volatile computer-readable storage medium endowed with instructions operable, upon execution by the processor, to cause the reader device to

detect responses exhibited by two or more of the analysis regions to the target analyte,

determine corresponding detection ranges of the two or more analysis regions, and

calculate, based at least on the detected responses and the corresponding detection ranges, a concentration of the target analyte in the subject.

51. The reader device of claim 50, the instructions further operable, upon execution by the processor, to cause the reader device to

capture an image of the implanted analyte sensor, and

analyze the captured image to detect the responses and/or to determine the corresponding detection ranges.

52. The reader device of claim 50, wherein the reader device is a mobile electronic device selected from the group consisting of a laptop, a tablet PC, or a mobile phone.

53. The reader device of claim 51, the instructions further operable, upon execution by the processor, to cause the reader device to select a portion of the captured image for analysis, wherein the selected portion of the captured image corresponds to one of the analysis regions of the implanted analyte sensor.

54. The reader device of claim 50, the instructions further operable, upon execution by the processor, to cause the reader device to

detect an orientation mark of the analyte sensor, and

orient the captured image based on the detected orientation mark.

55. The reader device of claim 50, the instructions further operable, upon execution by the processor, to cause the reader device to

detect an orientation mark or a control region of the analyte sensor, and

adjust a calculation of the target analyte concentration based on the detected orientation mark or control region.

56. The reader device of claim 50, the non-volatile computer-readable storage medium further endowed with a pre-determined pattern corresponding to the two or more analysis regions of the analyte sensor, the instructions further operable, upon execution by the processor, to cause the reader device to select one or more portions of the captured image for analysis based at least on the pre-determined pattern.

57. The reader device of claim 50, the non-volatile computer-readable storage medium further endowed with a pre-determined pattern corresponding to the two or more analysis regions of the analyte sensor, the instructions further operable, upon execution by the processor, to cause the reader device to

locate, based on the pre-determined pattern, one or more analysis regions of the implanted analyte sensor, and

selectively detect the responses from the located analysis regions of the implanted analyte sensor.

58. The reader device of claim 50, the non-volatile computer-readable storage medium further endowed with a look-up table, the instructions further operable, upon execution by the processor, to cause the reader device to determine the corresponding detection ranges of the two or more analysis regions based at least on the look-up table.

59. The reader device of claim 50, wherein at least two of the analysis regions are duplicate regions configured to exhibit substantially identical responses, the instructions further operable, upon execution by the processor, to cause the reader device to

compare responses of the duplicate regions,

determine a difference between the responses of the duplicate regions, and

determine, based on the difference, that one or more of the responses is inaccurate.

60. The reader device of claim 59, the instructions further operable, upon execution by the processor, to cause the reader device to determine, based on the difference, that the analyte sensor has a malfunction.

61. The reader device of claim 50, wherein at least one of the analysis regions is a control region configured to detect a second analyte, the instructions further operable, upon execution by the processor, to cause the reader device to

compare a response of the control region to a previous or pre-determined response,

determine a difference between the response and the previous or pre-determined response, and

determine, based on the difference, that one or more of the detected responses is inaccurate or that the analyte sensor has a malfunction.

62. The reader device of claim 51, the instructions further operable, upon execution by the processor, to cause the reader device to

select areas of the captured image for analysis, wherein the areas are selected based on one or more of color, intensity, a prior analyte sensor reading, pre-determined instructions, a pre-determined pattern, or a reference image.

63. The reader device of claim 62, wherein the concentration of the target analyte is calculated based at least on one or more of the sizes, number, shapes, locations, colors, or intensities of the selected areas.

64. The reader device of claim 50, the instructions further operable, upon execution by the processor, to cause the reader device to

determine, based at least on the detected responses, that the analyte sensor is leaking or malfunctioning, or determine a time frame for replacement of the analyte sensor, or correct the determined target analyte concentration.

65. A method of monitoring a concentration of a target analyte in the dermis of a subject, the method comprising:

positioning an analyte sensor at least partially within the dermis of the subject, wherein the analyte sensor includes two or more analysis regions configured to detect a target analyte within different concentration ranges, and wherein the two or more analysis regions have contiguous detection ranges and coextensive ranges of response;

detecting, by a reader device positioned above the dermis, responses exhibited by the two or more analysis regions; and

calculating, based at least on the detected responses, the concentration of the target analyte, wherein the reader device is a mobile electronic device selected from the group consisting of a laptop, a tablet PC, or a mobile phone.

66. The method of claim 65, wherein the analyte sensor includes one or more orientation marks, and wherein the method further including locating, by the reader device, the two or more analysis regions based on the one or more orientation marks.

67. The method of claim 65, further including determining, by the reader device, the detection ranges corresponding to the two or more analysis regions.

68. The method of claim 66, further including determining by the reader device, based at least on the one or more orientation marks, a variation in analyte sensor implantation depth, skin tone, or skin translucence, wherein determining the concentration of the target analyte further comprises adjusting the calculated concentration to compensate for said variation.

69. The method of claim 65, further including capturing, by the reader device, an image of the analyte sensor within the dermis, wherein detecting the responses exhibited by the two or more analysis regions comprises analyzing two or more portions of the captured image corresponding to each of the analysis regions of the analyte sensor.

70. The method of claim 65, further including implanting the analyte sensor within the dermis of the subject to a depth of 20-200 μ

m.

71. The method of claim 69, wherein detecting the responses exhibited by the two or more analysis regions includes selecting multiple areas within a portion of the captured image, and calculating the concentration of the target analyte includes calculating a representative value for each of the selected areas, wherein the portion of the image corresponds to one of said analysis regions.

72. The method of claim 77, wherein calculating the concentration of the target analyte includes calculating a representative value for each of the selected areas further comprises averaging at least some of the calculated representative values.