Method and apparatus using alternative site glucose determinations to calibrate and maintain noninvasive and implantable analyzers

• US 20040024553A1
• Filed: 02/28/2003
• Published: 02/05/2004
• Est. Priority Date: 03/08/2002
• Status: Active Grant

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Henderson, James R., Ruchti, Timothy L., Monfre, Stephen L., Hazen, Kevin H., Blank, Thomas B.
• Granted Patent: US 6,998,247 B2
• Time in Patent Office: Days
• US Class Current: 702/104
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

Methods for calibrating noninvasive or implantable glucose analyzers utilize either alternative invasive glucose determinations or noninvasive glucose determinations for calibrating noninvasive or implantable glucose analyzers. Use of an alternative invasive or noninvasive glucose determination in the calibration allows minimization of errors due to sampling methodology, and spatial and temporal variation that are built into the calibration model. An additional method uses statistical correlations between noninvasive and alternative invasive glucose determinations and traditional invasive glucose determinations to adjust noninvasive or alternative invasive glucose concentrations to traditional invasive glucose concentrations. The methods provide a means for calibrating on the basis of glucose determinations that reflect the matrix observed and the variable measured by the analyzer more closely. A glucose analyzer couples an invasive fingerstick meter to a noninvasive glucose analyzer for calibration, validation, adaptation, and safety check of the calibration model embodied in the noninvasive analyzer.

Claims

1. A method of controlling error in calibration of a noninvasive glucose analyzer comprising:

collecting one or more noninvasive signals from a subject'"'"'s body at an alternative sampling site;

determining an alternative reference glucose measurement corresponding to each noninvasive signal from said body at an alternative reference measurement site having a tissue matrix substantially identical or equivalent to a tissue matrix at said alternative sampling site and;

any of the steps of;

calibrating said glucose analyzer utilizing said one or more noninvasive signals and said reference glucose measurements; and

maintaining said glucose analyzer utilizing said one or more noninvasive signals and reference glucose measurements.

2. The method of claim 1, wherein said corresponding reference measurements comprise either alternative invasive or noninvasive measurements.

3. The method of claim 2, wherein said step of determining an alternative reference glucose measurement comprises determining an invasive reference glucose measurement utilizing any of:

a lancet;

a laser poration apparatus;

an applied current; and

a suction apparatus.

4. The method of claim 3, wherein said step of determining said invasive reference glucose measurement comprises utilizing a set of biosamples.

5. The method of claim 4, wherein said set of biosamples comprises any of:

a set of blood samples;

a set of interstitial fluid samples;

a set of selectively sampled interstitial fluid samples;

a set of samples wherein each sample is a mixture of a blood matrix, an interstitial fluid matrix, and a selectively sampled interstitial fluid matrix;

6. The method of claim 2, wherein said noninvasive reference measurements comprise one of:

a reference set of bioimpedence readings;

a reference set of Raman spectra;

a reference set of fluorescence spectra;

a reference set of ultraviolet spectra;

a reference set of visible spectra;

a reference set of near-infrared spectra; and

a reference set of infrared spectra.

7. The method of claim 1, wherein said alternative sampling site and said alternative reference measurement site each comprise one of:

a head;

an earlobe;

an eye;

a tongue;

a torso;

an abdominal region;

an arm;

an upper arm;

a forearm;

a volar aspect of a forearm;

a dorsal aspect of a forearm;

a palmar region;

a leg;

a thigh;

a calf; and

a plantar region.

8. The method of claim 1, wherein said alternative sampling site and said alternative reference measurement site each comprise a forearm.

9. The method of claim 1, wherein said reference region is within approximately three inches of said sampling region.

10. The method of claim 1, wherein said reference region is within approximately three inches of a contralateral position of said body compared to said first region.

11. The method of claim 1, wherein said step of calibrating comprises any of:

performing a partial least squares analysis;

performing a principal component regression analysis; and

performing a neural network analysis.

12. The method of claim 1, wherein said one or more noninvasive signals comprise any of:

a series of transmittance measurements;

a series of transflectance measurements; and

a series of diffuse reflectance measurements.

13. The method of claim 12, wherein said one or more noninvasive signals comprise any of:

a set of bioimpedence readings;

a set of Raman spectra;

a set of fluorescence spectra;

a set of ultraviolet spectra;

a set of visible spectra;

a set of near-infrared spectra; and

a set of infrared spectra.

14. The method of claim 13, wherein said set of near-infrared spectra are collected from 1100 to 2500 nm.

15. The method of claim 1, further comprising steps of:

collecting a prediction noninvasive signal; and

predicting a glucose concentration based on said prediction noninvasive signal and said calibrated glucose analyzer.

16. The method of claim 15, wherein said step of collecting a prediction noninvasive signal is performed on a prediction region of said body comprising one of:

said head;

said earlobe;

said eye;

said tongue;

said torso;

said abdominal region;

said arm;

said upper arm;

said forearm;

said volar aspect of the forearm;

said dorsal aspect of the forearm;

said palmar region;

said leg;

said thigh;

said calf; and

said plantar region.

17. The method of claim 16, wherein said step of collecting said prediction noninvasive signal comprises one of:

a transmittance measurement;

a transflectance measurement; and

a diffuse reflectance measurement.

18. The method of claim 17, wherein said prediction noninvasive signal comprises one of:

a bioimpedence reading;

a Raman spectrum;

a fluorescence spectrum;

an ultraviolet spectrum;

a visible spectrum;

a near-infrared spectrum; and

an infrared spectrum.

19. The method of claim 18, wherein said near-infrared spectrum is collected from 1100 to 2500 nm.

20. The method of claim 17, wherein said prediction region is said forearm.

21. The method of claim 1, wherein said step of maintaining comprises any of:

maintaining a glucose calibration;

adjusting a calibration;

performing a bias correction;

generating a calibration assignment;

(reference patent in text)

performing a validation;

performing a quality assurance procedure; and

performing a quality control procedure.

22. A method of accounting for sampling-related differences in blood glucose measurements comprising:

providing a transform that models a relationship between sets of glucose measurements wherein each set includes samples collected in a different manner; and

converting subsequent measurements according to said transform.

28. The method of claim 22, wherein said step of converting subsequent measurements comprises one of the steps of:

converting between traditional invasive measurements and alternative invasive measurements; and

converting between noninvasive measurements predicted from a calibration based on alternative invasive measurements, and traditional invasive measurements.

23. The method of claim 23, wherein said sets of glucose measurements comprise either a set of alternate invasive measurements and a set of traditional invasive measurements or a set of noninvasive and a set of traditional invasive measurements.

26. The method of claim 23, wherein said sets of measurements are generated during periodic testing after a carbohydrate load.

27. The method of claim 23, wherein subsequent measurements include any of:

single measurements; and

sets of measurements.

24. The method of claim 24, wherein said relationship includes any of:

a magnitude difference;

a lag;

a phase difference; and

a width difference.

25. The method of claim 25, wherein said transform embodies an algorithm, said algorithm comprising any of the steps of;

dividing a set of measurements by said magnitude difference;

subtracting said lag from a set of measurements;

subtracting said phase difference from a set of measurements; and

adjusting a set of alternative invasive glucose concentrations with said width difference.

29. An apparatus for measuring a tissue analyte in vivo, comprising

a first component configured to generate a noninvasive measurement of said tissue analyte;

a second component, configured to generate an invasive reference measurement of said tissue analyte, said first and second components electromagnetically coupled; and

means for using said reference measurement to optimize calibration of said apparatus.

30. The apparatus of claim 29, wherein said tissue analyte comprises glucose.

31. The apparatus of claim 30, wherein said second component comprises one of:

an alternative invasive glucose analyzer; and

a traditional invasive glucose analyzer.

32. The apparatus of claim 30, further comprising:

memory means for storing any of said measurements.

33. The apparatus of claim 32, wherein said means for optimizing said calibration comprises:

computer program means for optimizing said calibration, said program means embodied in said memory means; and

a processing element configured to execute said program means.

34. The apparatus of claim 33, said program means including program means for using a second calibration to adjust any of:

said apparatus calibration; and

a bias correction.

35. The apparatus of claim 34, where said second calibration is utilized in any of:

a calibration assignment;

a validation;

a quality assurance procedure; and

a quality control procedure.

36. The apparatus of claim 31, wherein said first component comprises a near-IR glucose analyzer.

37. The apparatus of claim 29, wherein said first component and said second component are integrated.

38. The apparatus of claim 29, wherein said first component and said second component are separate units.

39. The apparatus of claim 38, wherein said first component and said second component are wirelessly electromagnetically coupled.

40. The apparatus of claim 39, wherein said first component and said second component are wirelessly electromagnetically coupled through any of telemetry, infrared signals, and radiowaves.

41. A method of calibration, comprising

collecting spectra with a glucose analyzer from a first region on a subject'"'"'s body;

generating corresponding reference glucose concentrations from a second region on said subject'"'"'s body, so that a first set of paired data points is created;

collecting a second set of reference signals from said first region and correlating said second set of reference signals with said spectra, so that a second set of paired data points is created;

determining difference in glucose concentrations between corresponding reference values from said first set of paired data points and said second set of paired data points; and

selecting a calibration set of paired spectra and reference glucose concentration from said first set based on said difference.

42. The method of claim 41, wherein said signals comprise one of:

a set of alternative invasive signals;

a set of noninvasive signals;

a set of implantable signals;

43. The method of claim 42, wherein said set of noninvasive signals comprise:

a set of near-IR spectra;

44. The method of claim 43, wherein said set of near-IR spectra are collected in a range of approximately 1150 to 1850 nm.

45. The method of claim 41, wherein said reference glucose concentrations comprise one of:

a reference set of traditional invasive glucose concentrations;

a reference set of alternative invasive glucose concentrations;

a reference set of noninvasive glucose concentrations.

46. The method of claim 45, wherein said step of selecting comprises:

selecting said paired data points during a period of glucose stasis.

47. The method of claim 41, wherein said step of selecting data points comprises

selecting differences of less than 10 percent.

48. The method of claim 41, further comprising

perturbing circulation at said first site prior to collecting said signals, so that said difference in glucose concentration is reduced.

49. A method of controlling error in calibration of an implantable glucose analyzer comprising:

collecting one or more signals at a first site from a subject'"'"'s body using said implantable glucose analyzer;

determining a reference glucose measurement corresponding to each of said signals at a reference measurement site having perfusion characteristics the same or similar to said first site; and

any of the steps of;

calibrating said implantable glucose analyzer utilizing said one or more signals and said reference glucose measurements; and

maintaining said glucose analyzer utilizing said one or more signals and reference glucose measurements.

50. The method of claim 49, wherein said corresponding reference measurements comprise either invasive or noninvasive measurements.

51. The method of claim 50, wherein said step of determining an alternative reference glucose measurement comprises determining an invasive reference glucose measurement utilizing any of:

a lancet;

a laser poration apparatus;

an applied current; and

a suction apparatus.

52. The method of claim 51, wherein said step of determining said invasive reference glucose measurement comprises utilizing a set of biosamples.

53. The method of claim 52, wherein said set of biosamples comprises any of:

a set of blood samples;

a set of interstitial fluid samples;

a set of selectively sampled interstitial fluid samples;

a set of samples wherein each sample is a mixture of a blood matrix, an interstitial fluid matrix, and a selectively sampled interstitial fluid matrix;

54. The method of claim 50, wherein said noninvasive reference measurements comprise one of:

a reference set of bioimpedence readings;

a reference set of Raman spectra;

a reference set of fluorescence spectra;

a reference set of ultraviolet spectra;

a reference set of visible spectra;

a reference set of near-infrared spectra; and

a reference set of infrared spectra.

55. The method of claim 49, wherein said first site comprises a peritoneal cavity.

56. The method of claim 55, wherein said reference measurement site is located on one of:

a head;

an earlobe;

an eye;

a tongue;

a torso;

an abdominal region;

an arm;

an upper arm;

a forearm;

a volar aspect of a forearm;

a dorsal aspect of a forearm;

a palmar region;

a leg;

a thigh;

a calf; and

a plantar region.

57. The method of claim 49, wherein said step of calibrating comprises any of:

performing a partial least squares analysis;

performing a principal component regression analysis; and

performing a neural network analysis.

58. The method of claim 49, wherein said one or more signals comprise any of:

a series of transmittance measurements;

a series of transflectance measurements; and

a series of diffuse reflectance measurements.

59. The method of claim 58, wherein said one or more noninvasive signals comprise any of:

a set of bioimpedence readings;

a set of Raman spectra;

a set of fluorescence spectra;

a set of ultraviolet spectra;

a set of visible spectra;

a set of near-infrared spectra; and

a set of infrared spectra.

60. The method of claim 59, wherein said set of near-infrared spectra are collected from 1100 to 2500 nm.

61. The method of claim 49, further comprising steps of:

collecting a prediction signal; and

predicting a glucose concentration based on said prediction signal and said calibrated glucose analyzer.

62. The method of claim 61, wherein said step of collecting a prediction noninvasive signal is performed on a prediction region of said body comprising a peritoneal cavity.

63. The method of claim 62, wherein said step of collecting said prediction signal comprises one of:

a transmittance measurement;

a transflectance measurement; and

a diffuse reflectance measurement.

64. The method of claim 63, wherein said prediction signal comprises one of:

a bioimpedence reading;

a Raman spectrum;

a fluorescence spectrum;

an ultraviolet spectrum;

a visible spectrum;

a near-infrared spectrum; and

an infrared spectrum.

65. The method of claim 64, wherein said near-infrared spectrum is collected from 1100 to 2500 nm.

66. The method of claim 49, wherein said step of maintaining comprises any of:

maintaining a glucose calibration;

adjusting a calibration;

performing a bias correction;

generating a calibration assignment;

performing a validation;

performing a quality assurance procedure; and

performing a quality control procedure.