Reagentless optical analyte detection system

• US 8,204,565 B2
• Filed: 04/04/2006
• Issued: 06/19/2012
• Est. Priority Date: 04/04/2005
• Status: Active Grant

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: Arnold, Mark A., Olesberg, Jonathon T., Coretsopoulos, Chris
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US11/397,927
• Publication Number:
  US 20070066877A1
• Time in Patent Office: 2,268 Days
• Field of Search: 600309-344
• US Class Current: 600/310
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• 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

Disclosed is an implantable microspectrometer for the reagentless optical detection of an analyte in a sample fluid. The microspectrometer comprises an optical sampling cell having a cell housing defining a fluid inlet port and a fluid outlet port, the fluid inlet port configured to receive an optical sampling fluid from a test subject; an electromagnetic radiation source in communication with a first portion of the optical sampling cell housing and configured to irradiate at least a portion of the optical sampling fluid with electromagnetic radiation; and an electromagnetic radiation detector in communication with a second portion of the optical sampling cell housing and configured to detect electromagnetic radiation emanating from the optical sampling cell. In use, the implantable microspectrometer can optically detect at least one parameter of an analyte contained within the optical sampling fluid in the absence of an added reagent.

Claims

1. An implantable microspectrometer, comprising:

an optical sampling cell within a cell housing, said cell housing further defining a fluid inlet port and a fluid outlet port, the fluid inlet port configured to receive an optical sampling fluid from a test subject;

an electromagnetic radiation source in communication with a first portion of the optical sampling cell housing and configured to irradiate at least a portion of the optical sampling fluid with electromagnetic radiation; and

an electromagnetic radiation detector in communication with a second portion of the optical sampling cell housing and configured to detect electromagnetic radiation emanating from the optical sampling cell,

wherein the implantable microspectrometer can optically detect at least one parameter of an analyte contained within the optical sampling fluid in the absence of a reagent, and wherein the implantable microspectrometer occupies a total volume in the range of from about 0.01 cm³ to about 1.0 cm³.

2. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation source comprises a light emitting diode.

3. The implantable microspectrometer of claim 2, wherein the light emitting diode comprises GaInAsSb.

4. The implantable microspectrometer of claim 2, wherein the light emitting diode comprises a cascade of two or more p-i-n junction emitter regions.

5. The implantable microspectrometer of claim 2, wherein the light emitting diode exhibits a maximum voltage draw less than about 4.0 volts and a maximum current draw less than about 30 mA.

6. The implantable microspectrometer of claim 5, wherein the infrared electromagnetic radiation is in the spectral range of from 4000 cm⁻

1 to 6500 cm<sup>−

1</sup>.

7. The implantable microspectrometer of claim 5, wherein the infrared electromagnetic radiation is in the spectral range of from 300 cm⁻

1 to 4000 cm<sup>−

1</sup>.

8. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation source is configured to generate infrared electromagnetic radiation.

9. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation source is connected to the first portion of the optical sampling cell housing.

10. The implantable microspectrometer of claim 1, wherein the radiation detector comprises a photodiode array comprising a plurality of photodiode detector elements.

11. The implantable microspectrometer of claim 10, wherein the photodiode array comprises an array of from 16 to 64 photodiode detector elements.

12. The implantable microspectrometer of claim 10, wherein the photodiode array has a specific detectivity of from about 10⁸ cmHz^1/2 watt to about 10¹² cmHz^1/2 watt.

13. The implantable microspectrometer of claim 10, wherein the photodiode array comprises a plurality of solid state p-i-n photo diodes.

14. The implantable microspectrometer of claim 13, wherein the plurality of solid state p-i-n photodiodes comprise GaInAsSb, InGaAs, PbS, PbSe, or any combination thereof.

15. The implantable microspectrometer of claim 14, wherein the infrared electromagnetic radiation is in the spectral range of from 4000 cm⁻

1 to 6500 cm<sup>−

1</sup>.

16. The implantable microspectrometer of claim 14, wherein the infrared electromagnetic radiation is in the spectral range of from 300 cm⁻

1 to 4000 cm<sup>−

1</sup>.

17. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation detector is configured to detect infrared electromagnetic radiation.

18. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation detector is capable of substantially continuous operation while maintaining a detector temperature less than about 100°

F.

19. The implantable microspectrometer of claim 18, wherein the bandpass filter comprises a passband width of from approximately 12 cm⁻

1 to approximately 20 cm<sup>−

1</sup>.

20. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation detector comprises a bandpass filter.

21. The implantable microspectrometer of claim 1, wherein the electromagnetic radiation detector is connected to the second portion of the optical sampling cell housing.

22. The implantable microspectrometer of claim 1, wherein the optical sampling cell housing is comprised of an electromagnetic radiation transparent material.

23. The implantable microspectrometer of claim 22, wherein the electromagnetic radiation transparent material comprises a fluoropolymer.

24. The implantable microspectrometer of claim 1, wherein the optical sampling cell is substantially cylindrical in shape.

25. The implantable microspectrometer of claim 24, wherein the optical sampling cell has a diameter in the range of from approximately 150 μ

m to approximately 250 μ

m, an optical path length in the range of from approximately 0.5 mm to approximately 1.5 mm, and an interior volume in the range of from approximately 25 nL to approximately 35 nL.

26. The implantable microspectrometer of claim 1, wherein the optical sampling cell is substantially rectangular in shape.

27. The implantable microspectrometer of claim 1, further comprising a vacuum source in communication with the fluid outlet port of the sampling cell and configured to generate a flow of fluid sample from the test subject, through the fluid inlet port, through the optical sampling cell, and through the fluid outlet port.

28. The implantable microspectrometer of claim 27, wherein the vacuum source is configured to generate a flow of fluid sample having a flow rate in the range of from about 30 nL/min to about 150 nL/min.

29. The implantable microspectrometer of claim 1, further comprising a fluid sampling assembly in communication with the sample fluid inlet port and configured to obtain a fluid sample containing an analyte from a test subject.

30. The implantable microspectrometer of claim 29, wherein the fluid sampling assembly comprises an implantable ultrafiltration probe.

31. The implantable microspectrometer of claim 29, wherein the fluid sampling assembly comprises an implantable microdialysis probe.

32. The implantable microspectrometer of claim 29, wherein the fluid sampling assembly is configured to obtain an interstitial fluid sample from the test subject.

33. The implantable microspectrometer of claim 1, wherein the optical detection of at least one parameter of an analyte contained within the optical sampling fluid comprises the detection of electromagnetic radiation absorption, reflection, scattering, or a combination thereof.

34. The implantable microspectrometer of claim 1, wherein at least one component of the microspectrometer is in electronic communication with an electronic support unit.

35. An implantable microspectrometer for the reagentless optical detection of an analyte in fluid sample, comprising

an optical sampling cell within a cell housing, said cell housing further defining a fluid inlet port and a fluid outlet port, the fluid inlet port configured to receive an optical sampling fluid from a test subject;

a means for generating electromagnetic radiation, whereby the means for generating radiation is in communication with a first portion of the optical sampling cell housing and configured to irradiate at least a portion of the optical sampling fluid with electromagnetic radiation;

a means for detecting electromagnetic radiation, whereby the means for detecting electromagnetic radiation is in communication with a second portion of the optical sampling cell housing and configured to detect electromagnetic radiation emanating from the optical sampling cell,

wherein the implantable microspectrometer can optically detect at least one parameter of an analyte contained within the optical sampling fluid in the absence of a reagent, and wherein the implantable microspectrometer occupies a total volume in the range of from about 0.01 cm³ to about 1.0 cm³.

36. A method for the reagentless optical detection of an analyte in a fluid sample, comprising the steps of:

providing a microspectrometer, comprising;

(i) an optical sampling cell within a cell housing, said cell housing further defining a fluid inlet port and a fluid outlet port, the fluid inlet port;

(ii) an electromagnetic radiation source in communication with a first portion of the optical sampling cell housing; and

(iii) an electromagnetic radiation detector in communication with a second portion of the optical sampling cell housing;

obtaining a fluid sample containing an analyte from a test subject;

conveying the obtained fluid sample through the inlet port in to the optical sampling cell;

generating electromagnetic radiation from the electromagnetic radiation source and irradiating at least a portion of the fluid sample within the optical sampling cell;

optically detecting electromagnetic radiation emanating from the optical sampling cell with the electromagnetic radiation detector; and

returning at least a portion of the obtained fluid sample contained within the optical sampling cell to the test subject,

wherein the microspectrometer occupies a total volume in the range of from about 0.01 cm³ to about 1.0 cm³.

37. The method of claim 36, wherein the fluid sample is a biological fluid.

38. The method of claim 36, wherein the analyte comprises glucose, urea, creatinine, phosphate, sulfate, or a mixture thereof.

39. The method of claim 36, wherein the analyte comprises glucose.

40. The method of claim 36, wherein the fluid sample comprises blood.

41. The method of claim 36, wherein the fluid sample comprises interstitial fluid.

42. The method of claim 36, further comprising implanting the optical sampling cell subcutaneously in the test subject.

43. The method of claim 36 or 42, wherein the fluid sample is obtained from the subcutaneous tissue bed surrounding the peritoneal cavity of a mammalian test subject.

44. The method of claim 36, wherein the electromagnetic radiation detector comprises a photodiode array connected to the optical sampling cell.

45. The method of claim 36, further comprising applying a negative pressure gradient to the optical sampling cell to convey the obtained sample fluid to the optical sampling cell.

46. The method of claim 36 or 45, wherein the portion of the fluid sample conveyed to the optical sampling cell is irradiated with infrared electromagnetic radiation.

47. The method of claim 46, wherein the infrared electromagnetic radiation is in the spectral range of from 4000 cm⁻

1 to 6500 cm<sup>−

1</sup>.

48. The method of claim 46, wherein the infrared electromagnetic radiation is in the spectral range of from 300 cm⁻

1 to 4000 cm<sup>−

1</sup>.