Non-invasive measurement of blood analytes using photodynamics

• US 6,889,069 B2
• Filed: 08/15/2003
• Issued: 05/03/2005
• Est. Priority Date: 09/13/2001
• Status: Expired due to Fees

• Current Assignee: Fovioptics Incorporated
• Original Assignee: Fovioptics Incorporated
• Inventors: Routt, Wilson, Rice, Mark J.
• Primary Examiner(s): Winakur, Eric F
• Assistant Examiner(s): Kremer, Matthew
• Application Number:
  US10/642,104
• Publication Number:
  US 20040147820A1
• Time in Patent Office: 627 Days
• Field of Search: 600/316, 600/319, 600/365, 600/318
• US Class Current: 600/319
• CPC Class Codes: A61B 3/12 for looking at the eye fundus, e.g. ophthalmoscopes A61B3/13 takes precedence
• 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 5/14558 by polarisation

Abstract

The determination of blood glucose in an individual is carried out by projecting illuminating light into an eye of the individual to illuminate the retina with the light having wavelengths that are absorbed by rhodopsin and with the intensity of the light varying in a prescribed temporal manner. The light reflected from the retina is detected to provide a signal corresponding to the intensity of the detected light, and the detected light signal is analyzed to determine the changes in form from that of the illuminating light. For a biased sinusoidal illumination, these changes can be expressed in terms of harmonic content of the detected light. The changes in form of the detected light are related to the ability of rhodopsin to absorb light and regenerate, which in turn is related to the concentration of blood glucose, allowing a determination of the relative concentration of blood glucose. Other photoreactive analytes can similarly be determined by projecting time varying illuminating light into the eye, detecting the light reflected from the retina, and analyzing the detected light signal to determine changes in form of the signal due to changes in absorptivity of a photoreactive analyte.

Claims

1. A method for determining blood glucose level in an individual, comprising:

measuring a regeneration rate of a retinal visual pigment of the individual; and

determining the blood glucose level of the individual using the measured regeneration rate of the retinal visual pigment.

2. The method according to claim 1 wherein the retinal visual pigment is rod rhodopsin.

3. The method according to claim 1 wherein the retinal visual pigment is cone rhodopsin.

4. The method according to claim 3 wherein the cone rhodopsin has an absorption band peak at 430 nm.

5. The method according to claim 3 wherein the cone rhodopsin has an absorption band peak at 550 nm.

6. The method according to claim 3 wherein the cone rhodopsin has an absorption band peak at 585 nm.

7. A method of calculating an individual'"'"'s blood glucose level, comprising:

altering the reflectance of the individual'"'"'s retina;

measuring the rate of change of the reflectance of the individual'"'"'s retina; and

correlating the rate of change of the reflectance of the individual'"'"'s retina to the individual'"'"'s blood glucose level.

8. The method according to claim 7 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with light.

9. The method according to claim 8 wherein illuminating the retina with light comprises illuminating the retina with steady state light.

10. The method according to claim 8 wherein illuminating the retina with light comprises illuminating the retina with modulated light.

11. The method according to claim 8 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with a light having a wavelength range that includes the active absorption band of a retinal visual pigment.

12. The method according to claim 11 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with a light having a wavelength range that includes the active absorption band of more than one retinal visual pigment.

13. The method according to claim 12 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with a light having a wavelength range that includes the active absorption band of more than one cone visual pigment.

14. The method according to claim 11 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with a light having a wavelength range that includes the active absorption band of one cone visual pigment and one rod visual pigment.

15. The method according to claim 7 wherein altering the reflectance of an individual'"'"'s retina comprises illuminating the retina with a light having a wavelength consistent with a wavelength known to activate rhodopsin in areas of the retina illuminated by the light.

16. The method according to claim 7 wherein the measuring the rate of change of the reflectance of the individual'"'"'s retina occurs during the altering the reflectance of the individual'"'"'s retina.

17. A The method according to claim 7 the measuring the rate of change of the reflectance of the individual'"'"'s retina occurs subsequent to the altering the reflectance of the individual'"'"'s retina.

18. A method for determining blood glucose level in an individual, comprising:

illuminating a portion of the retina comprising substantially only cones to reduce the amount of a visual pigment in the portion of the retina comprising substantially only cones;

measuring a rate of regeneration of the visual pigment in the portion of the retina comprising substantially only cones; and

calculating the individual'"'"'s blood glucose level utilizing the measured rate of regeneration of visual pigment in the portion of the retina comprising substantially only cones.

19. A method for determining blood glucose according to claim 18 wherein illuminating a portion of the retina is performed using an illuminating source having a conical view of the retina of between 5 and 30 degrees.

20. A method for determining blood glucose according to claim 18 wherein illuminating a portion of the retina is performed using an illuminating source having a conical view of less than 10 times the angle subtended by the portion of the retina with the greatest cone density.

21. A method for determining blood glucose according to claim 18 wherein the portion of the retina comprising substantially only cones subtends an angle of 3 degrees.

22. A method for determining blood glucose according to claim 18 wherein the portion of the retina comprising substantially only cones is the fovea centralis.

23. A method for measuring blood glucose level in an individual, comprising:

illuminating a portion of the retina positioned outside the normal retinal vasculature to alter the concentration of a visual pigment in the portion of the retina;

measuring a rate of change of regeneration of the visual pigment concentration in the portion of the retina outside the retinal vasculature; and

determining the blood glucose level of the individual based on the measured rate of change of regeneration of visual pigment.

24. The method according to claim 23 wherein the portion of the retina positioned outside of the normal retinal vasculature comprises more cones than rods.

25. The method according to claim 23 wherein the portion of the retina positioned outside of the normal retinal vasculature comprises the fovea.

26. The method according to claim 25 wherein the portion of the retina positioned outside of the normal retinal vasculature comprises the fovea centralis.

27. The method according to claim 23 wherein illuminating a portion of the retina comprises illuminating a portion of the retina with a light having a wavelength range that includes the active absorption band of a retinal visual pigment.

28. The method according to claim 23 wherein illuminating a portion of the retina comprises illuminating a portion of the retina with a light having a wavelength range that includes the active absorption band of more than one retinal visual pigment.

29. The method according to claim 23 wherein illuminating a portion of the retina comprises illuminating a portion of the retina with a light having a wavelength range that includes the active absorption band of more than one cone visual pigment.

30. The method according to claim 23 wherein illuminating a portion of the retina comprises illuminating a portion of the retina with a light having a wavelength range that includes the active absorption band of one cone visual pigment and one rod visual pigment.

31. The method according to claim 23 wherein illuminating a portion of the retina comprises illuminating a portion of the retina with a light having a wavelength consistent with a wavelength known to activate rhodopsin in areas of the fovea illuminated by the light.