METHOD FOR NON-INVASIVE BLOOD GLUCOSE MONITORING AND METHOD FOR ANALYSING BIOLOGICAL MOLECULE

• US 20120277557A1
• Filed: 04/27/2012
• Published: 11/01/2012
• Est. Priority Date: 04/29/2011
• Status: Active Grant

• Current Assignee: Taiwan Biophotonic Corporation
• Original Assignee: Industrial Technology Research Institute
• Inventors: Li, Yu-Tang, Chu, Chang-Sheng, Fan, Chih-Hsun, Chung, Shuang-Chao, Tiao, Kuo-Tung, Li, Ming-Chia, Chen, Jyh-Chern
• Granted Patent: US 9,743,864 B2
• Time in Patent Office: Days
• US Class Current: 600/319
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14558 by polarisation

Abstract

A method for non-invasive blood glucose monitoring includes the following steps. At least one ray of light is emitted from at least one light source. The light emitted from the light source is leaded into an eyeball and focused on the eyeball through a first beam splitter. The reflected light reflected from the eyeball is transmitted through the first beam splitter to a set of photo detectors. Optical rotatory distribution (ORD) information and absorption energy information of the reflected light transmitted to the set of photo detectors are measured. ORD difference and absorption energy difference resulting from the light emitted from the light source and the reflected light transmitted to the set of photo detectors are obtained. Glucose information is obtained by analyzing the ORD difference and the absorption energy difference, and since glucose information has a corresponding relationship with blood glucose information, blood glucose information may be read.

Claims

1. A method for non-invasive blood glucose monitoring comprising:

emitting at least one ray of light from at least one light source;

leading the light emitted from the light source into an eyeball and focusing on the eyeball through a first beam splitter with a focusing function, such that a reflected light reflected from the eyeball is generated;

transmitting the reflected light reflected from the eyeball to a set of photo detectors through the first beam splitter;

measuring an optical rotatory distribution information and an absorption energy information of the reflected light transmitted to the set of photo detectors through the set of photo detectors;

processing the optical rotatory distribution information and the absorption energy information to obtain an optical rotatory distribution difference and an absorption energy difference resulting from the light emitted from the light source and the reflected light transmitted to the set of photo detectors through processing the optical rotatory distribution information and the absorption energy information; and

analyzing the optical rotatory distribution difference and the absorption energy difference to obtain a biological molecule information of a biological molecule, wherein the biological molecule at least comprises a glucose, a glucose information is obtained through the biological molecule, and since the glucose information has a corresponding relationship with a blood glucose information, the blood glucose information is read according to the relationship.

2. The method for non-invasive glucose monitoring as recited in claim 1, wherein an apparatus which obtained and analyzed the optical rotatory distribution difference and the absorption energy difference comprises a processing unit.

3. The method for non-invasive glucose monitoring as recited in claim 2, wherein the processing unit comprises an analog digital circuit integration module, wherein the analog digital circuit integration module comprises a microprocessor, an amplifier and an analog digital converter.

4. The method for non-invasive glucose monitoring as recited in claim 3, wherein the analog digital circuit integration module further comprises a wireless transmission device.

5. The method for non-invasive glucose monitoring as recited in claim 1 further comprising controlling an optical characteristic of the light source, an opto-element offset or the combination thereof, wherein the optical characteristic of the light source comprises using the light source to control an emitting frequency of the light, an intensity of the light, a length of turn-on time of the light, a length of turn-off time of the light, or a combination thereof.

6. The method for non-invasive glucose monitoring as recited in claim 1 further comprising detecting a light information of the light from the first beam splitter, before the light is leaded into the eyeball, to perform a feedback control on the optical characteristic of the light.

7. The method for non-invasive glucose monitoring as recited in claim 6, wherein the light information comprises at least one of an energy information and a position information.

8. The method for non-invasive glucose monitoring as recited in claim 6, wherein an apparatus for detecting the light information comprises at least one of an optical power meter and an optic sensor.

9. The method for non-invasive glucose monitoring as recited in claim 6, wherein an apparatus for performing feedback control on the optical characteristic comprises a processing unit, an alarm or a light source control unit.

10. The method for non-invasive glucose monitoring as recited in claim 1, wherein the biological molecule comprises a cholesterol, an uric acid, a water, a lactic acid, an urea, an ascorbic acid, or a combination thereof.

11. The method for non-invasive glucose monitoring as recited in claim 1, wherein the biological molecule comprises an interference molecule.

12. The method for non-invasive glucose monitoring as recited in claim 11, wherein a step for obtaining the glucose information comprises removing the interference caused by the interference molecule.

13. The method for non-invasive glucose monitoring as recited in claim 1, wherein the first beam splitter focuses the light to an anterior chamber of the eyeball, and the reflected light reflected from the eyeball comprises the reflected light reflected from the aqueous humor.

14. The method for non-invasive glucose monitoring as recited in claim 1, wherein the set of photo detectors comprises an optical rotatory distribution measuring device and an energy measuring device, which are respectively measuring the reflected light reflected from the eyeball.

15. The method for non-invasive glucose monitoring as recited in claim 1 further comprising transmitting the reflected light reflected from the aqueous humor to a second beam splitter through the first beam splitter and then transmitting to the set of photo detectors through the second beam splitter.

16. The method for non-invasive glucose monitoring as recited in claim 15, wherein the set of photo detectors comprises a first photo detector and a second photo detector, which are respectively used to measure the reflected light reflected from or passed through the second beam splitter.

17. The method for non-invasive glucose monitoring as recited in claim 16, wherein the first photo detector and the second photo detector respectively comprise an optical rotatory distribution measuring device and an energy measuring device.

18. The method for non-invasive glucose monitoring as recited in claim 16, wherein one of the first photo detector and the second photo detector is an optical rotatory distribution measuring device, and another one of the first photo detector and the second photo detector is an energy measuring device.

19. The method for non-invasive glucose monitoring as recited in claim 1, wherein the measuring of the optical rotatory distribution difference by the set of photo detectors comprises an active optical rotatory distribution measuring device and a passive optical rotatory distribution measuring device.

20. The method for non-invasive glucose monitoring as recited in claim 19, wherein the active optical rotatory distribution method comprises using an analyzer to calculate the optical rotatory distribution information, directly.

21. The method for non-invasive glucose monitoring as recited in claim 19, wherein the passive optical rotatory distribution measuring method comprises using at least one passive optical rotatory distribution measuring device to calculate the optical rotatory distribution information, wherein the passive optical rotatory distribution measuring device comprises a polarizer, and the passive optical rotatory distribution measuring device calculates the optical rotatory distribution information by measuring an energy of the reflected light passed through the polarizer.

22. The method for non-invasive glucose monitoring as recited in claim 1 further comprising an eye-alignment position device for aligning the sight of an eye with the eye-alignment position device to determine a measuring position of the eyeball.

23. A method for analyzing biological molecule comprising:

establishing at least one first polynomial equation representing a relationship between a biological molecule and an optical rotatory distribution difference, and at least one second polynomial equation representing a relationship between the biological molecule and an absorption energy, wherein the biological molecule comprises a target molecule and at least one interference molecule, and a plurality of variables of the first polynomial equation and the second polynomial equation respectively comprises a target molecule concentration variable and a interference molecule concentration variable; and

substituting the optical rotatory distribution difference and the absorption energy difference measured by an apparatus for biological molecule monitoring into the first polynomial equation and the second polynomial equation to calculate a first target molecule concentration of the target molecule which simultaneously exists in the target molecule and the interference molecule.

24. The method for analyzing biological molecule as recited in claim 23, wherein a method for calculating the first target molecule concentration comprise solving the simultaneous equations of the first polynomial equation and the second polynomial equation.

25. The method for analyzing biological molecule as recited in claim 23, wherein the first polynomial equation is established from a plurality of biological molecule concentration values and a plurality of corresponding optical rotatory distribution difference values stored in a database, and the second polynomial equation is established from the biological molecule concentration values and a plurality of corresponding absorption energy difference values stored in the database.

26. The method for analyzing biological molecule as recited in claim 25, wherein a plurality of samples of the biological molecule concentration values stored in the database comprises a plurality of live samples or a plurality of standard sample.

27. The method for analyzing biological molecule as recited in claim 23, wherein a method for obtaining the optical rotatory distribution difference comprises:

discarding a portion of the optical rotatory distribution difference values that exceeded an acceptable variation range measured by the apparatus for biological molecule monitoring; and

calculating the optical rotatory distribution values using at least one mathematical statistical method.

28. The method for analyzing biological molecule as recited in claim 27, wherein the mathematical statistical method comprises a least square error regression analysis method.

29. The method for analyzing biological molecule as recited in claim 27, wherein the acceptable variation range comprises a range of the arithmetic mean of the optical rotatory distribution difference values×

(1±

15%).

30. The method for analyzing biological molecule as recited in claim 23, wherein a method for obtaining the absorption energy difference comprises:

discarding a portion of the absorption energy difference values that exceeded an acceptable variation range measured by the apparatus for biological molecule monitoring; and

calculating the absorption energy difference values using at least one mathematical statistical method.

31. The method for analyzing biological molecule as recited in claim 30 wherein the mathematical statistical method comprises a least square error regression analysis method.

32. The method for analyzing biological molecule as recited in claim 30 wherein the acceptable variation range comprises a range of the arithmetic mean of the absorption energy difference values×

(1±

15%).

33. The method for analyzing biological molecule as recited in claim 23, wherein the steps of establishing the first polynomial equation and the second polynomial equation further comprises:

distinguishing between a plurality of optical rotatory distribution difference ranges and a plurality of absorption energy difference ranges, having the first polynomial equation correspondingly used in each of the optical rotatory distribution difference ranges, and having the second polynomial equation correspondingly used in each of the absorption energy ranges.

34. The method for analyzing biological molecule as recited in claim 23, wherein the step for calculating the first target molecule concentration further comprises:

analyzing the optical rotatory distribution difference and the absorption energy difference through controlling a change factor to obtain the first target molecule concentration, and the change factor comprises a light emitting frequency, a light energy intensity, a length of turn-on time of the light, a length of turn-off time of the light, an opto-element offset, or a combination thereof.

35. The method for analyzing biological molecule as recited in claim 23 further comprising:

establishing at least one first graph or at least one third polynomial equation representing a relationship between the biological molecule and the optical rotatory distribution, wherein the variable of the third polynomial equation comprises the target molecule concentration variable;

subsisting the optical rotatory distribution difference measured by the apparatus for biological molecule monitoring into the first graph, the third polynomial equation or the combination thereof to calculate a second target molecule concentration of the target molecule; and

determining a final target molecule concentration through the first target molecule concentration and the second target molecule concentration.

36. The method for analyzing biological molecule as recited in claim 35, wherein the first graph and the third polynomial equation are established from a plurality of biological molecule concentration values and a plurality of corresponding optical rotatory distribution difference values stored in a database.

37. The method for analyzing biological molecule as recited in claim 35, wherein the steps for establishing the first graph or the third polynomial equation further comprise:

distinguishing a plurality of optical rotatory distribution difference ranges, having the first graph, the third polynomial equation, or the combination thereof correspondingly used in each of the optical rotatory distribution difference ranges.

38. The method for analyzing biological molecule as recited in claim 35 further comprising:

establishing at least one second graph or at least one fourth polynomial equation representing a relationship between the biological molecule and the absorption energy, wherein the variable of the fourth polynomial equation comprises the target molecule concentration variable;

subsisting the absorption energy difference measured by the apparatus for biological molecule monitoring into the second graph, the fourth polynomial equation or the combination thereof to calculate a third target molecule concentration of the target molecule; and

determining a final target molecule concentration through the first target molecule concentration, the second target molecule concentration, the third target molecule concentration, or the combination thereof.

39. The method for analyzing biological molecule as recited in claim 38, wherein the second graph and the fourth polynomial equation are established from a plurality of biological molecule concentration values and a plurality of corresponding absorption energy difference values stored in a database.

40. The method for analyzing biological molecule as recited in claim 38, wherein the steps for establishing the second graph or the fourth polynomial equation further comprise:

distinguishing a plurality of absorption energy difference ranges, having the second graph, the fourth polynomial equation, or the combination thereof correspondingly used in each of the absorption energy difference ranges.

41. The method for analyzing biological molecule as recited in claim 23 further comprising:

establishing at least one second graph or at least one third polynomial equation representing a relationship between the biological molecule and the absorption energy, wherein the variable of the fourth polynomial equation comprises the target molecule concentration variable;

subsisting the absorption energy difference measured by the apparatus for biological molecule monitoring into the second graph, the fourth polynomial equation or the combination thereof to calculate a third target molecule concentration of the target molecule; and

determining a final target molecule concentration through the first target molecule concentration and the third target molecule concentration.

42. The method for analyzing biological molecule as recited in claim 41, wherein the second graph and the fourth polynomial equation are established from a plurality of biological molecule concentration values and a plurality of corresponding absorption energy difference values stored in a database.

43. The method for analyzing biological molecule as recited in claim 41, wherein the steps for establishing the second graph or the fourth polynomial equation further comprise:

distinguishing a plurality of absorption energy difference ranges, having the second graph, the fourth polynomial equation, or the combination thereof correspondingly used in each of the absorption energy difference ranges.

44. The method for analyzing biological molecule as recited in claim 23, wherein the biological molecule comprises a glucose, a cholesterol, an uric acid, a water, a lactic acid, an urea, an ascorbic acid, or a combination thereof.

45. The method for analyzing biological molecule as recited in claim 23, wherein the analytical method is performed with a processing unit of the apparatus for biological molecule monitoring.