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

• US 6,998,247 B2
• Filed: 02/28/2003
• Issued: 02/14/2006
• Est. Priority Date: 03/08/2002
• Status: Expired due to Fees

• 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.
• Primary Examiner(s): GITOMER, RALPH J
• Application Number:
  US10/377,916
• Publication Number:
  US 20040024553A1
• Time in Patent Office: 1,082 Days
• Field of Search: 435/14, 250/339.09, 250/339.11, 250/252.1, 250/341.5, 356/39
• US Class Current: 435/14
• 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 sample site disparity 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, said alternative sampling site having a location that is among those sites that are selected when performing an alternative invasive glucose determination, said alternative sampling site being located at a region other than said subject'"'"'s fingertips or toes;

invasively determining an alternative reference glucose measurement corresponding in time to each noninvasive signal from said body at an alternative reference measurement site, said alternative reference measurement site located at a region of the body having a tissue matrix substantially identical or equivalent to a tissue matrix at said alternative sampling site so that error due to a discrepancy between glucose concentration at said alternative sampling site and said alternative reference measurement site is reduced or eliminated, and;

any of the steps of;

calibrating said glucose analyzer utilizing a calibration model calculated from said one or more noninvasive signals and said alternative reference glucose measurements; and

maintaining calibration of said glucose analyzer by utilizing said one or more noninvasive signals and said alternative reference glucose measurements to select, adjust and/or correct a calibration model.

2. The method of claim 1, wherein said step of invasively determining said alternative reference glucose measurement comprises determining one or more alternative reference glucose measurements utilizing any of:

a lancet;

a laser poration apparatus;

an applied current; and

a suction apparatus.

3. The method of claim 2, wherein said step of determining said one or more alternative reference glucose measurements comprises measuring one or more invasive reference glucose measurements on each of a set of biosamples.

4. The method of claim 3, wherein said set of biosamples comprises any of:

a set of blood samples;

a set of interstitial fluid samples;

a set of interstitial fluid samples selectively sampled from a tissue depth approximately equal to a depth of penetration of an incident signal; and

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.

5. The method of claim 1, wherein said noninvasive signals comprise one of:

a reference set of bioimpedance 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;

a set of infrared spectra;

a reference set of far-infrared spectra; and

a reference set of mid-infrared spectra.

6. 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.

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

8. The method of claim 1, wherein said alternative reference measurement site is within approximately three inches of said alternative sampling site.

9. The method of claim 1, wherein said alternative reference measurement site is within approximately three inches of a contralateral position of said body compared to said alternative sampling site.

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

performing a partial least squares analysis;

performing a partial least squares analysis;

performing a principal component regression; and

performing a neural network analysis.

11. 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.

12. The method of claim 11, 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;

a set of infrared spectra;

a set of far-infrared spectra; and

a set of mid-infrared spectra.

13. The method of claim 12, wherein said set of near-infrared spectra are collected from 1100 to 2500 nm.

14. 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 glucose analyzer calibrated using said one or more noninvasive signals and said alternative reference glucose measurements.

15. The method of claim 14, 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 palmer region;

said leg;

said thigh;

said calf; and

said planter region.

16. The method of claim 15, wherein said step of collecting said prediction noninvasive signal comprises one of:

a transmittance measurement;

a transflectance measurement; and

a diffuse reflectance measurement.

17. The method of claim 16, 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;

a set of infrared spectra;

a set of far-infrared spectra; and

a set of mid-infrared spectra.

18. The method of claim 17, wherein said near-infrared spectrum is collected from 1100 to 2500 nm.

19. The method of claim 16, wherein said prediction region is said forearm.

20. 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;

performing a validation;

performing a quality assurance procedure; and

performing a quality control procedure.

21. A method of controlling sample site disparity error in calibration of an implantable glucose analyzer, comprising the steps of:

collecting one or more signals at a first site from a subject'"'"'s body using said implantable glucose analyzer, said first site being located at a region other than said subject'"'"'s fingertips or toes;

determining an alternative reference glucose measurement corresponding in time to each of said one or more signals from said body at an alternative reference measurement site, said alternative reference measurement site located at a region of the body having a tissue matrix substantially identical or equivalent to a tissue matrix at said first site so that error due to a discrepancy between glucose concentration at said first site and said alternative reference measurement site is reduced or eliminated, and;

any of the steps of;

calibrating said glucose analyzer utilizing a calibration model calculated from said one or more signals and said alternative reference glucose measurements; and

maintaining calibration of said glucose analyzer by utilizing said one or more signals and reference glucose measurements to select, adjust and/or correct a calibration model.

22. The method of claim 21, wherein said step of determining said 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.

23. The method of claim 22, wherein said step of determining said invasive reference glucose measurements comprises measuring one or more invasive reference glucose measurements on each of a set of biosamples.

24. The method of claim 23, wherein said set of biosamples comprises any of:

a set of blood samples;

a set of interstitial fluid samples;

a set of interstitial fluid samples selectively sampled from a tissue depth approximately equal to a depth of penetration of an incident signal;

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.

25. The method of claim 21, wherein said alternative reference glucose measurements comprises any 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;

a set of infrared spectra;

a set of far-infrared spectra; and

a set of mid-infrared spectra.

26. The method of claim 21, wherein said first site comprises a peritoneal cavity.

27. The method of claim 26, wherein said alternative reference measurement site is located on any 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.

28. The method of claim 21, wherein said step of calibrating further comprises any of the steps of:

performing a partial least squares analysis;

performing a principal component regression analysis; and

performing a neural network analysis.

29. The method of claim 21, 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.

30. The method of claim 29, wherein said one or more 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;

a set of infrared spectra;

a set of far-infrared spectra; and

a set of mid-infrared spectra.

31. The method of claim 30, wherein said set of near-infrared spectra are collected from 1100 to 2500 nm.

32. The method of claim 21, further comprising steps of:

collecting a prediction signal; and

predicting a glucose concentration based on said prediction signal and said glucose analyzer calibrated using said one or more signals and said alternative reference glucose measurements.

33. The method of claim 32, wherein said step of collecting a prediction signal is performed on a prediction region of said body comprising a peritoneal cavity.

34. The method of claim 33, wherein said step of collecting said prediction signal comprises one of:

a transmittance measurement;

a transflectance measurement; and

a diffuse reflectance measurement.

35. The method of claim 34, 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;

a set of infrared spectra;

a set of far-infrared spectra; and

a set of mid-infrared spectra.

36. The method of claim 35, wherein said near-infrared spectrum is collected from 1100 to 2500 nm.

37. The method of claim 21, 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.