Non-invasive tissue glucose level monitoring

• US 6,721,582 B2
• Filed: 02/20/2001
• Issued: 04/13/2004
• Est. Priority Date: 04/06/1999
• Status: Expired due to Fees

• Current Assignee: Cercacor Laboratories
• Original Assignee: Argose, Inc.
• Inventors: Trepagnier, Pierre, Kollias, Nikiforos, Mansfield, James, Brand, Derek, Hopmeier, Michael J., Freeman, Jenny
• Primary Examiner(s): Hindenburg, Max F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US09/785,547
• Publication Number:
  US 20020016534A1
• Time in Patent Office: 1,148 Days
• Field of Search: 600/309-310, 600/322-326, 600/316, 600/473, 600/476
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0062 Arrangements for scanning
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• 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 5/443 Evaluating skin constituents, e.g. elastin, melanin, water
• CPC Class Codes: A61B 5/444 Evaluating skin marks, e.g. mole, nevi, tumour, scar
• CPC Class Codes: A61B 5/445 Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore

Abstract

Instruments and methods are described for performing non-invasive measurements of analyte levels and for monitoring, analyzing and regulating tissue status, such as tissue glucose levels.

Claims

1. A non-invasive glucose monitoring instrument comprising:

a radiation source for directing excitation radiation to a portion of a tissue surface wherein said source emits excitation radiation at a plurality of different wavelengths of ultraviolet or visible light that excites a target to emit radiation, such that the radiation emitted from the excited target and received at the tissue surface correlates with a glucose level of the tissue;

a radiation detector positioned to receive the radiation emitted from the tissue surface, wherein the radiation detector is configured to synchronously scan radiation emitted by the target with the excitation radiation; and

analyzing means operatively connected to the radiation detector for analyzing radiation detected by the radiation detector and translating said detected radiation to an indication of the tissue glucose level,

wherein the target is selected from the group consisting of a structural matrix tissue component, a cellular tissue component, a mitochondrial tissue component, a collagen cross link, a pepsin-digestible collagen cross link, a collagenase-digestible collagen cross link, a non-pepsin digestible collagen cross link, an elastin cross link, a tryptophan-containing protein, NADH, FAD a flavoprotein, and any combination thereof.

2. The instrument of claim 1 which comprises a sync 50 scan.

3. The instrument of claim 1 which comprises an excitation emission map.

4. The instrument of claim 1 where the included excitation wavelengths excite 370 nm and 460 nm.

5. The instrument of claim 1 wherein the radiation source is operative to emit radiation at between about 285 and 305 nm and the radiation detector is operative to detect radiation at between about 315 and 420 nm.

6. The instrument of claim 1 wherein the radiation source is operative to emit radiation at between about 330 and 345 nm and the radiation detector is operative to detect radiation at between about 370 and 410 nm.

7. The instrument of claim 1 wherein the radiation source is operative to emit radiation at between about 330 and 360 nm and the radiation detector is operative to detect radiation at between about 400 and 550 nm.

8. The instrument of claim 1 wherein the radiation source is operative to emit radiation at between about 330 and 500 nm and the radiation detector is operative to detect radiation at between about 500 and 560 nm.

9. The instrument of claim 1 further comprising a normalizing detector responsive to another target that provides normalizing information to said processing circuit to normalize the indicated glucose level.

10. The instrument of claim 1 further comprising normalizing means which provides normalizing information to said analyzing means to normalize the indicated glucose level.

11. The instrument of claim 10 wherein said normalizing means normalizes for age, UV damage, skin color, temperature, perfusion, hydration, pH and combinations thereof.

12. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the excitation radiation is at two wavelengths of about 370 and 460 nm.

13. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the excitation radiation is at a wavelength of about 590 nm.

14. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the excitation radiation is at a wavelength of about 670-680 nm.

15. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the excitation radiation is at two wavelengths of about 740 and 920 nm.

16. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the excitation radiation is a combination of subsets of the region of 280-1,100 nm.

17. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the radiation detected from the excited target is between about 340 and 400 nm.

18. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the radiation detected from the excited target is between about 400 and 550 nm.

19. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the radiation detected from the excited target is between about 500 and 560 nm.

20. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the radiation detected from the excited target is a combination of subsets of the region of 340-560 nm.

21. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, the method further comprising normalizing the glucose level determined.

22. The method of claim 21 wherein normalizing comprises normalizing for one or more variables selected from the group consisting of temperature, degree of perfusion, age, UV damage, skin color temperature, hydration, and pH.

23. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, the method further comprising measuring scattering and absorbance and adjusting the glucose level.

24. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein said step of determining the glucose level comprises analyzing the radiation detected using one or more multi variate analysis methodologies selected from a group comprising PLS, PCR, LDA, MLR, stepwise LR and combinations thereof.

25. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein said step of exciting comprises irradiating a target with excitation radiation at a plurality of wavelengths and the step of detecting radiation comprises the step of synchronously scanning the emitted radiation and excitation radiation.

26. A non-invasive method of detecting a glucose level of a tissue comprising:

exciting a non-glucose target in the tissue with ultraviolet radiation or visible light wherein the excited target emits radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient;

detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and

determining said glucose level from the radiation detected, wherein the step of exciting comprises application of a probe to the skin, said probe comprising a radiation source and, wherein a position of the probe on the skin is varied during detecting.