Implantable sensor and system for in vivo measurement and control of fluid constituent levels

• US 6,049,727 A
• Filed: 04/03/1998
• Issued: 04/11/2000
• Est. Priority Date: 07/08/1996
• Status: Expired due to Term

• Current Assignee: Animas Corporation (Johnson & Johnson)
• Original Assignee: Animas Corporation (Johnson & Johnson)
• Inventors: Crothall, Katherine D.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/054,806
• Time in Patent Office: 739 Days
• Field of Search: 600/310, 600/316, 600/322, 600/326, 600/473, 600/476, 604/50, 604/66, 604/67, 604/890.1, 604/891.1, 356/39
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• 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 5/6876 Blood vessel
• CPC Class Codes: A61B 5/6884 Clamps or clips
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01N 2021/3144 for oxymetry
• CPC Class Codes: G01N 2021/3148 using three or more wavelengths
• CPC Class Codes: G01N 2021/399 Diode laser
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 2201/084 Fibres for remote transmission
• CPC Class Codes: G01N 2201/127 Calibration; base line adjustment; drift compensation

Abstract

An in vivo implantable sensor obtains spectra of body fluid constituents and processes the spectra to determine the concentration of a constituent of the body fluid. The sensor includes an optical source and detector. The source emits light at a `plurality of different, discrete wavelengths, including at least one wavelength in the infrared region. The light interacts with the body fluid and is received at the detector. The light at the plurality of different wavelengths has a substantially collinear optical path through the fluid with respect to each other. When measuring fluid constituents in a blood vessel, such as blood glucose, the light at the plurality of different wavelengths is emitted in a substantially single period of time. The spectra is corrected for artifacts introduced from extraneous tissue in the optical path between the source and the detector. The sensor is fully implanted and is set in place to allow plural measurements to be taken at different time periods from a single in vivo position. The light source emits at at least three different wavelengths.

Claims

1. A method of determining a concentration of a constituent of body fluid in a mammal using in vivo spectroscopy, the method comprising the step of:

(a) implanting a sensor system in the mammal by setting the sensor system in place to allow plural measurements to be taken at different time periods from a single in vivo position, the sensor system including a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another;

(b) emitting light from the source;

(c) obtaining a signal at an output of the detector which contains spectra of the body fluid at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of the constituent of the body fluid.

2. A method according to claim 1 wherein step (a) includes positioning the sensor system so that the infrared light passes through body fluid containing the at least one constituent and extraneous tissue, step (c) includes obtaining composite spectra which includes spectra of the fluid and spectra of the tissue, the tissue spectra resulting from the extraneous tissue, and step (d) further includes correcting for the spectra of the tissue.

3. A method according to claim 2 wherein step (d) includes:

(i) applying a pathlength correction to the composite spectra;

(ii) applying a baseline correction to the composite spectra;

(iii) multiplying the pathlength and baseline corrected composite spectra by beta coefficients and adding a constant thereto to obtain a concentration of the at least one constituent which is uncorrected for the tissue spectra; and

(iv) applying best linear fit coefficients to the uncorrected concentration of the at least one constituent of the body fluid to obtain a concentration of the at least one constituent which is corrected for the tissue spectra.

4. A method according to claim 3 further comprising, prior to performing step (d), determining the beta coefficients in vitro by the steps of:

(i) collecting in vitro fluid samples from a statistically significant plurality of mammals;

(ii) obtaining spectra of the fluid samples using a scanning or FT-IR spectrophotometer having a white light source;

(iii) correlating the spectra of the in vitro samples to the concentration of the at least one constituent measured using non-spectroscopic means; and

(iv) selecting a finite number of discrete wavelengths and respective beta coefficients which provide a best least-squares fit of the spectra of the in vitro samples to the measured concentration of the at least one constituent.

5. A method according to claim 4 wherein the step of selecting the beta coefficients and the respective discrete wavelengths further includes the steps of:

(v) initially guessing for the discrete wavelengths by either selecting wavelengths with correlation coefficients in step (iii) that are as close as possible to +1 or -1 or by selecting wavelengths which have the largest beta coefficients in absolute value as determined in a Partial Least Squares routine;

(vi) optimizing the beta coefficients for the initial guessed wavelengths; and

(vii) sequentially varying each wavelength and reiteratively optimizing the beta coefficients to produce the least-squares fit, thereby obtaining an optimized set of discrete wavelengths and beta coefficients.

6. A method according to claim 2 wherein step (d) includes:

(i) subtracting a representative spectra of extraneous tissue from the composite spectra to obtain the fluid spectra;

(ii) applying a pathlength correction to the fluid spectra;

(ii) applying a baseline correction to the fluid spectra; and

(iii) multiplying the pathlength and baseline corrected fluid spectra by beta coefficients and adding a constant thereto to obtain a concentration of the at least one constituent.

7. A method according to claim 1 wherein step (b) includes emitting light at the different wavelengths at a substantially single period of time.

8. A method according to claim 7 wherein the substantially single period of time is less than about 100 microseconds.

9. A method according to claim 1 wherein the body fluid is blood, and step (a) includes positioning the implantable sensor system extravascularly, the source and the detector being arranged so that the light output from the source interacts with a blood vessel before being received by the detector, and step (d) includes analyzing the signal to determine the concentration of at least one blood constituent.

10. A method according to claim 9 wherein step (d) includes analyzing the signal to determine the concentration of blood glucose.

11. A method according to claim 1 wherein the body fluid is blood, and step (a) includes positioning the implantable sensor system around a vascular membrane, the source and the detector being arranged so that the light output from the source interacts with the vascular membrane before being received by the detector, and step (d) includes analyzing the signal to determine the concentration of at least one blood constituent in the vascular membrane.

12. A method according to claim 11 wherein step (d) includes analyzing the signal to determine the concentration of blood glucose.

13. A method according to claim 1 wherein the body fluid is interstitial fluid or gel, and step (a) includes positioning the implantable sensor system in a region of the body containing interstitial fluid or gel, the source and the detector being arranged so that the light output from the source interacts with the interstitial fluid or gel before being received by the detector, and step (d) includes analyzing the signal to determine the concentration of at least one constituent of the interstitial fluid or gel.

14. A method according to claim 13 wherein step (d) includes analyzing the signal to determine the concentration of glucose in the interstitial fluid or gel.

15. A method according to claim 1 wherein in step (b), the light emitted from the source has wavelengths in the near-infrared region.

16. A method according to claim 15 wherein all of the emitted wavelengths are in the near-infrared region.

17. A method according to claim 1 wherein step (b) includes sequentially emitting light at the different wavelengths from the source in a pulsed manner, light from all of the wavelengths being emitted within a substantially single period of time.

18. A method according to claim 1 wherein the detector of the sensor system is arranged to receive light transmitted through the body fluid, and the signal obtained in step (c) includes the transmitted light.

19. A method according to claim 1 wherein the detector of the sensor system is arranged to receive light reflected or scattered by the body fluid, and the signal obtained in step (c) includes the reflected or scattered light.

20. A method according to claim 1 wherein the source has a plurality of individual source elements, each source element emitting a different wavelength, and step (b) includes emitting the light from the plurality of individual source elements.

21. A method according to claim 1 further comprising the step of:

(e) measuring the output power of the source, wherein step (d) includes the step of obtaining an absorbance spectra by taking a log of the ratio of the detector output signal of step (c) and the output power of the source for each of the different wavelengths.

22. A method according to claim 1 wherein the source of light emits at at least three different wavelengths, and step (b) includes emitting the light from the source at at least the three different wavelengths.

23. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another, the source and detector adapted to be fully implanted and set in place to allow plural measurements to be taken at different time periods from a single in vivo position; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the body fluid.

24. A sensor according to claim 23 further comprising:

(d) a controller for causing the source to emit light at the different wavelengths within a substantially single period of time.

25. A sensor according to claim 24, wherein the substantially single period of time is less than about 100 microseconds.

26. A sensor according to claim 23, wherein the source includes a plurality of individual source elements, each source element emitting light at a different wavelength in the infrared region.

27. A sensor according to claim 26, wherein the individual source elements include laser diodes.

28. A sensor according to claim 27, wherein the individual source elements include light emitting diodes.

29. A sensor according to claim 23, wherein the source includes:

(i) a plurality of individual source elements each emitting light at one of the different wavelength in the infrared region; and

(ii) single core multimode optical fiber for receiving the light at the emitted wavelengths, the output of the optical fiber being the emitted output of the source, wherein the optical fiber has a length sufficient to allow for substantial wavelength mixing as light at the emitted wavelengths travels through the optical fiber towards an output end of the optical fiber, the wavelength mixing creating the substantially collinear optical path through the fluid for the different wavelengths with respect to one another.

30. A sensor according to claim 29, wherein the length of the optical fiber is greater than 1 meter.

31. A sensor according to claim 23, wherein the source includes:

(i) a plurality of individual source elements, each emitting light at one of the different wavelength in the infrared region; and

(ii) a diffraction grating coupler for receiving the light at the emitted wavelengths and outputting the light at the different wavelengths in a substantially collinear optical path with respect to one another, the output of the diffraction grating coupler being the emitted output of the source.

32. A sensor according to claim 23, wherein the source includes a tunable laser for emitting light at the different wavelengths, the tunable laser being programmed to scan through the different wavelengths.

33. A sensor according to claim 23, wherein the source includes:

(i) a broadband light which simultaneously emits light which includes at least the different wavelengths; and

(ii) a tunable spectral filter disposed between the output of the broadband light and the output of the source, the tunable spectral filter being programmed to scan through the different wavelengths.

34. A sensor according to claim 23, wherein the source includes a broadband light source which simultaneously emits light having a spectra that includes at least the different wavelengths, and the detector includes:

(i) a single collection optical fiber for receiving broadband light which has interacted with the body fluid;

(ii) a fixed grating for receiving the broadband light which has interacted with the body fluid and spectrally separating the received broadband light into a plurality of predefined wavelengths; and

(iii) a plurality of photodetectors, wherein each photodetector detects light at one of the predefined wavelengths.

35. A sensor according to claim 23, wherein light at the different wavelengths is output in a time-sequenced manner, and the detector includes a single photodetector which processes the light at the different wavelengths in coordination with the time-sequencing.

36. A sensor according to claim 23, wherein the source emits light at wavelengths in the near-infrared region from about 1,000 nanometers to about 2,500 nanometers.

37. A sensor according to claim 23, wherein the detector of the sensor system is arranged to receive light transmitted through the fluid, and the signal analyzed by the processor includes the directly transmitted light.

38. A sensor according to claim 23, wherein the detector of the sensor system is arranged to receive light reflected or scattered by the fluid, and the signal analyzed by the processor includes the reflected or scattered light.

39. A sensor according to claim 23, wherein the detector includes a photodetector.

40. A sensor according to claim 23, wherein the source includes a plurality of individual source elements arranged in close proximity to each other relative to the distance between the individual elements and the detector, so that the plurality of source elements define the substantially collinear optical path.

41. A sensor according to claim 23, wherein the sensor includes a plurality of individual source elements, each individual source element being frequency modulated at a unique predetermined frequency.

42. A sensor according to claim 23, wherein the sensor includes a calibration detector for detecting the output power of the source, the detected output power being communicated to the processor for use in the signal analysis.

43. A sensor according to claim 23, wherein the processor includes an output signal for indicating that the concentration of the at least one chemical constituent is outside of a predetermined range.

44. A sensor according to claim 23, wherein the source of the light emits at at least three different wavelengths.

45. An infusion pump system for monitoring at least one chemical constituent of body fluid in a mammal and delivering medication to the mammal, the system comprising:

(a) an implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor including;

(i) a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(ii) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the plurality of different wavelengths, wherein the source and the detector are adapted to be located so that (1) the light output from the source interacts with a body fluid before being received by the detector, and (2) light from each of the plurality of different wavelengths has a substantially collinear optical path through the fluid with respect to one another; and

(iii) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent of the body fluid; and

(b) a pump module connected to the sensor for dispensing doses of medicine in response to the concentration of the chemical constituent output from the processor.

46. A system according to claim 45, wherein the sensor further comprises:

(iv) a controller for causing the source to emit the light at the plurality of different wavelengths within a substantially single period of time.

47. A system according to claim 45, wherein the sensor determines the concentration of blood glucose in a body fluid of the mammal, and the medication dispenser is an insulin infusion pump for dispensing doses of insulin.

48. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a chamber which has a porosity sufficient to allow interstitial fluid or gel to pass therethrough but which inhibits adjacent tissue and solid material from passing therethrough;

(b) a source of light disposed within the chamber that emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(c) a detector disposed within the chamber and spaced from the source for detecting light emitted from the source and outputting a signal which contains spectra of the interstitial fluid or gel at each of the plurality of different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with the interstitial fluid or gel before being received by the detector, and (ii) light from each of the plurality of different wavelengths has a substantially collinear optical path through the interstitial fluid or gel with respect to one another; and

(d) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the interstitial fluid or gel.

49. A method of determining a concentration of a constituent of body fluid in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal, the sensor system including a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with a body fluid containing the at least one constituent before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another, the sensor system being positioned so that the infrared light also passes through extraneous tissue;

(b) emitting light from the source;

(c) obtaining a signal at an output of the detector which contains a composite spectra including spectra of the body fluid at each of the different wavelengths, and spectra of the tissue at each of the different wavelengths, the tissue spectra resulting from the extraneous tissue; and

(d) analyzing the signal to determine the concentration of the constituent of the body fluid, the analysis including correcting for the spectra of the tissue.

50. A method according to claim 49, wherein step (d) includes:

(i) applying a pathlength correction to the composite spectra;

(ii) applying a baseline correction to the composite spectra;

(iii) multiplying the pathlength and baseline corrected composite spectra by beta coefficients and adding a constant thereto to obtain a concentration of the at least one constituent which is uncorrected for the tissue spectra; and

(iv) applying best linear fit coefficients to the uncorrected concentration of the at least one constituent of the body fluid to obtain a concentration of the at least one constituent which is corrected for the tissue spectra.

51. A method according to claim 50 further comprising, prior to performing step (d), determining the beta coefficients in vitro by the steps of:

(i) collecting in vitro fluid samples from a statistically significant plurality of mammals;

(ii) obtaining spectra of the fluid samples using a scanning or FT-IR spectrophotometer having a white light source;

(iii) correlating the spectra of the in vitro samples to the concentration of the at least one constituent measured using non-spectroscopic means; and

(iv) selecting a finite number of discrete wavelengths and respective beta coefficients which provide a best least-squares fit of the spectra of the in vitro samples to the measured concentration of the at least one constituent.

52. A method according to claim 51, wherein the step of selecting the beta coefficients and the respective discrete wavelengths further includes the steps of:

(v) initially guessing for the discrete wavelengths by either selecting wavelengths with correlation coefficients in step (iii) that are as close as possible to +1 or -1 or by selecting wavelengths which have the largest beta coefficients in absolute value as determined in a Partial Least Squares routine;

(vi) optimizing the beta coefficients for the initial guessed wavelengths; and

(vii) sequentially varying each wavelength and reiteratively optimizing the beta coefficients to produce the least-squares fit, thereby obtaining an optimized set of discrete wavelengths and beta coefficients.

53. A method according to claim 49, wherein step (d) includes:

(i) subtracting a representative spectra of extraneous tissue from the composite spectra to obtain the fluid spectra;

(ii) applying a pathlength correction to the fluid spectra;

(iii) applying a baseline correction to the fluid spectra; and

(iv) multiplying the pathlength and baseline corrected fluid spectra by beta coefficients and adding a constant thereto to obtain a concentration of the at least one constituent.

54. A method of determining a concentration of blood glucose in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal, the sensor system being positioned extravascularly, the sensor system including a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with blood in a blood vessel before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the blood vessel with respect to one another;

(b) emitting light from the source;

(c) obtaining a signal at an output of the detector which contains spectra of the blood at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of glucose in the blood.

55. A method of determining a concentration of blood glucose in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal, the sensor system being positioned around a vascular membrane, the sensor system including a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with blood in the vascular membrane before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the vascular membrane with respect to one another;

(b) emitting light from the source;

(c) obtaining a signal at an output of the detector which contains spectra of the blood at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of glucose in the vascular membrane.

56. A method of determining a concentration of a constituent of interstitial fluid or gel in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal in a region of the body containing interstitial fluid or gel, the sensor system including a source of light which emits at a plurality of different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with the interstitial fluid or gel before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the interstitial fluid or gel with respect to one another;

(b) emitting light from the source;

(c) obtaining a signal at an output of the detector which contains spectra of the interstitial fluid or gel at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of at least one constituent of the interstitial fluid or gel.

57. A method according to claim 56, wherein step (d) includes analyzing the signal to determine the concentration of glucose in the interstitial fluid or gel.

58. A method of determining a concentration of a constituent of body fluid in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal, the sensor system including a source of light which emits at a plurality of different wavelengths in the near-infrared region from about 1,000 nanometers to about 2,500 nanometers, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another;

(b) emitting light from the source in the near-infrared region from about 1,000 nanometers to about 2,500 nanometers;

(c) obtaining a signal at an output of the detector which contains spectra of the body fluid at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of the constituent of the body fluid.

59. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at a plurality of different wavelengths, the source including;

(i) a plurality of individual source elements, each emitting light at a different wavelength in the infrared region, and

(ii) a diffraction grating coupler for receiving the light at the emitted wavelengths and outputting the light at the different wavelengths in a substantially collinear optical path with respect to one another, the output of the diffraction grating coupler being the emitted output of the source;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the body fluid.

60. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at plurality of different wavelengths, at least one of the wavelengths being in the infrared region, the source including a broadband light source which simultaneously emits light having a spectra that includes at least the different wavelengths;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, the detector including;

(i) a single collection optical fiber for receiving broadband light which has interacted with the body fluid;

(ii) a fixed grating for receiving the broadband light which has interacted with the body fluid and spectrally separating the received broadband light into a plurality of predefined wavelengths; and

(iii) a plurality of photodetectors, wherein each photodetector detects light at one of the predefined wavelengths,

wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the body fluid.

61. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at plurality of different wavelengths in the near-infrared region from about 1,000 nanometers to about 2,500 nanometers;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the body fluid.

62. An implantable sensor adapted for determining a concentration of blood glucose in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with blood in a blood vessel before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the blood vessel with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of glucose in the blood.

63. An implantable sensor adapted for determining a concentration of blood glucose in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the blood at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with blood in a vascular membrane before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the vascular membrane with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of glucose in the blood.

64. An implantable sensor adapted for determining a concentration of a chemical constituent of interstitial fluid or gel in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at plurality of different wavelengths, at least one of the wavelengths being in the infrared region;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the interstitial fluid or gel at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with the interstitial fluid or gel before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the interstitial fluid or gel with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the interstitial fluid or gel.

65. An implantable sensor according to claim 64, wherein the processor is adapted to analyze the signal to determine the concentration of glucose in the interstitial fluid or gel.

66. A method of determining a concentration of a constituent of body fluid in a mammal using in vivo spectroscopy, the method comprising the steps of:

(a) implanting a sensor system in the mammal, the sensor system including a source of light which emits at at least three different wavelengths, at least one of the wavelengths being in the infrared region, and a detector for detecting light emitted from the source, the source and the detector located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another;

(b) emitting light from the source at at least the three different wavelengths;

(c) obtaining a signal at an output of the detector which contains spectra of the body fluid at each of the different wavelengths; and

(d) analyzing the signal to determine the concentration of the constituent of the body fluid.

67. An implantable sensor adapted for determining a concentration of a chemical constituent of body fluid in a mammal using in vivo spectroscopy, the sensor comprising:

(a) a source of light which emits at at least three different wavelengths, at least one of the wavelengths being in the infrared region;

(b) a detector for detecting light emitted from the source and outputting a signal which contains spectra of the body fluid at each of the different wavelengths, wherein the source and the detector are adapted to be located so that (i) the light output from the source interacts with a body fluid before being received by the detector, and (ii) light from each of the different wavelengths has a substantially collinear optical path through the fluid with respect to one another; and

(c) a processor for analyzing the signal and the spectra, and determining therefrom the concentration of the chemical constituent in the body fluid.