Method and system for sensing glucose concentration

• US 10,188,332 B2
• Filed: 01/04/2018
• Issued: 01/29/2019
• Est. Priority Date: 02/16/2017
• Status: Active Grant

• Current Assignee: National Cheng KUNG University (Government of The Republic of China)
• Original Assignee: National Cheng KUNG University (Government of The Republic of China)
• Inventors: Lo, Yu-Lung, Phan, Quoc-Hung, Liao, Chia-Chi
• Primary Examiner(s): Punnoose, Roy M
• Application Number:
  US15/862,611
• Publication Number:
  US 20180228415A1
• Time in Patent Office: 390 Days
• Field of Search: 356364
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 3/102 for optical coherence tomography [OCT]
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14558 by polarisation
• CPC Class Codes: A61B 5/7235 Details of waveform analysis A61B5/349 takes precedence
• CPC Class Codes: G01J 3/447 Polarisation spectrometry
• CPC Class Codes: G01J 4/04 Polarimeters using electric detection means G01J4/02 takes precedence

Abstract

A system for sensing glucose concentration is provided and includes following components. A light source generates a light beam. The system may include a polarization state generator (PSG) for changing the polarization of the light beam, and then the light beam is emitted to a biological tissue. A polarization state analyzer (PSA) receives the light beam reflected from the biological tissue, and the received light beam is used to calculate Stokes vectors. A Mueller matrix is calculated according to the Stokes vectors. In some embodiments, the system includes an optical coherence tomography (OCT) in which the light beam is sensed by a detector for calculating the Mueller matrix. An optical rotation angle and a depolarization index are calculated in accordance with the differential Mueller matrix formalism. The glucose concentration is calculated in accordance with the optical rotation angle and the depolarization index.

Claims

1. A system for sensing glucose concentration, the system comprising:

a light source configured to generate a light beam;

a polarization state generator configured to receive the light beam, wherein the polarization state generator comprises a modulator for changing a polarization of the light beam, and the light beam passing the modulator is emitted to a biological tissue;

a polarization state analyzer configured to receive the light beam reflected from the biological tissue; and

a controlling module configured to transmit an electrical signal to the modulator, wherein the electrical signal has n sampling points which correspond to n polarizations of the light beam respectively, the n polarizations are different from each other, and n is a positive integer greater than or equal to 4,

wherein for each of the n sampling points, the controlling module calculates a Stokes vector according to the light beam received by the polarization state analyzer,

wherein the controlling module calculates a Mueller matrix according to the Stokes vectors corresponding to the n sampling points, and calculates at least one parameter according to the Mueller matrix, wherein the at least one parameter comprises a depolarization index or an optical rotation angle,

wherein the controlling module calculates a glucose concentration corresponding to the biological tissue according to the at least one parameter.

2. The system of claim 1, wherein the polarization state generator further comprises:

a polarizer disposed between the modulator and the light source, wherein a principal axis of the polarizer is 0°

; and

a quarter-wave plate disposed between the modulator and the biological tissue, wherein a principal axis of the quarter-wave plate is 0°

,

wherein a principal axis of the modulator is 45°

.

3. The system of claim 1, wherein the polarization state generator further comprises:

a polarizer disposed between the modulator and the light source;

a quarter-wave plate disposed between the modulator and the biological tissue; and

a half-wave plate disposed between the quarter-wave plate and the biological tissue.

4. The system of claim 3, wherein the modulator is an electro-optic modulator, a principal axis of the polarizer is 0°

, a principal axis of the electro-optic modulator is 45°

, a principal axis of the quarter-wave plate is 45°

, and a principal axis of the half-wave plate is 45°

,

wherein a Stokes vector of the light beam emitted by the polarization state generator is represented by following equations (1) and (2);

5. The system of claim 4, wherein the polarization state analyzer comprises:

a second electro-optic modulator with a principal axis of 0°

;

a third electro-optic modulator with a principal axis of 45°

, wherein the second electro-optic modulator is disposed between the biological tissue and the third electro-optic modulator;

an analyzer with a principal axis of 0°

; and

a detector, wherein the analyzer is disposed between the third electro-optic modulator and the detector, and the detector is configured to receive the light beam passing through the second electro-optic modulator, the third electro-optic modulator, and the analyzer.

6. The system of claim 5, wherein the controlling module performs a Fourier transform on brightness of the light beam received by the detector to obtain a plurality of brightness parameters, and calculates a plurality of Stokes parameters of the corresponding Stokes vector according to the plurality of brightness parameters.

7. The system of claim 6, wherein the controlling module calculates a differential Mueller matrix according to following equations (3) and (4):

8. The system of claim 7, wherein the controlling module generates a differential Mueller matrix m_Δ

as a following equation (5) according to the differential Mueller matrix m;

9. The system of claim 8, wherein the controlling module substitutes the optical rotation angle into a linearly increasing function to obtain the glucose concentration, or substitutes the depolarization index into a linearly decreasing function to obtain the glucose concentration.

10. The system of claim 8, wherein the controlling module obtains an optical path length in accordance with a following equation (8):

Δ

=e<sup>−

L/l</sup> 

 

(8)

wherein Δ

is the depolarization index, L is a length of the sample, and l is the optical path length,

wherein the controlling module calculates the glucose concentration corresponding to the sample in accordance with a following equation (9);

11. A method for sensing glucose concentration for a system which comprises a light source, a polarization state generator and a polarization state analyzer, wherein a light beam generated by the light source is emitted to the polarization state generator and then is emitted to a biological tissue, the polarization state analyzer receives the light beam reflected from the biological tissue, and the method comprises:

transmitting an electrical signal to a modulator of the polarization state generator, wherein the electrical signal has n sampling points which correspond to n polarizations of the light beam respectively, the n polarizations are different from each other, and n is a positive integer greater than or equal to 4;

calculating a Stokes vector according to the light beam received by the polarization state analyzer for each of the n sampling points; and

calculating a Mueller matrix according to the Stokes vectors corresponding to the n sampling points, calculating at least one parameter according to the Mueller matrix, and calculating a glucose concentration corresponding to the biological tissue according to the at least one parameter, wherein the at least one parameter comprises a depolarization index or an optical rotation angle.

12. A system for sensing glucose concentration, the system comprising:

a light source configured to generate a light beam;

an optical coherence tomography (OCT) device configured to receive the light beam, wherein the optical coherence tomography comprises at least one detector; and

a controlling module, calculating a Muller matrix according to signals received by the at least one detector, and calculating an optical rotation angle and a depolarization index according to the Muller matrix, and calculating a glucose concentration corresponding to a sample according to the optical rotation angle and the depolarization index.

13. The system of claim 12, wherein the optical coherence tomography device comprises:

a polarization state generator, configured to receive the light beam and change a polarization of the light beam;

a first detecting module, configured to compensate the light beam and split the light beam;

a second detecting module, coupled to the first detecting module and configured to split the light beam;

a reference arm, disposed at a side of the second detecting module; and

a measurement arm, disposed at another side of the second detecting module.

14. The system of claim 13,

wherein the polarization stage generator comprises:

a polarizer and a quarter-wave plate, configured to receive light; and

a plurality of first lens disposed between the light source and the polarizer and the quarter-wave plate,

wherein the first detecting module comprises;

a first non-polarizing beam splitter (NPBS) having a first side, a second side, a third side and a fourth side, wherein the first side is opposite to the third side, the second side is opposite to the fourth side, and the polarizer and the quarter-wave plater are disposed at the first side of the first NPBS;

a first mirror, disposed at the second side of the first NPBS;

a first dispersion compensator disposed between the first mirror and the first NPBS;

a first detector, disposed at the fourth side of the first NPBS;

a second lens disposed between the first NPBS and the first detector,

wherein the second detecting module comprises;

a second NPBS, disposed at the third side of the first NPBS and having a first side, a second side, a third side and a fourth side, wherein the first side of the second NPBS is opposite to the third side of the second NPBS, the second side of the second NPBS is opposite to the fourth side of the second NPBS;

a second detector, disposed at the fourth side of the second NPBS;

a third lens, disposed between the second NPBS and the second detector; and

a first compensator, disposed between the second NPBS and the third lens,

wherein the reference arm comprises;

a scanning stage, disposed at the second side of the second NPBS;

a second mirror, disposed between the scanning stage and the second NPBS;

a variable wave plater, disposed between the second mirror and the second NPBS; and

a second compensator, disposed between the second NPBS and the variable wave plater,

wherein the measurement arm comprises;

a sample stage, disposed at the third side of the second NPBS;

a third mirror, disposed between the second NPBS and the sample stage;

the sample, disposed between the third mirror and the second NPBS; and

a second dispersion compensator, disposed between the second NPBS and the sample.

15. The system of claim 14, wherein the first compensator comprises two quarter-wave plates and one half-wave plate,

wherein the second compensator comprises two quarter-wave plates and one half-wave plate.

16. The system of claim 15, wherein the controlling module rotates the quarter-wave plate and the polarizer, and adjusts the variable wave plate to produce at least 16 interferometric signals detected by the second detector,

wherein the controlling module calculates the Muller matrix according to the 16 interferometric signals.

17. The system of claim 16, wherein the controlling module obtains an optical path length in accordance with a following equation (1):

Δ

=e<sup>−

L/l</sup> 

 

(1)

wherein Δ

is the depolarization index, L is a length of the sample, and l is the optical path length,

wherein the controlling module calculates the glucose concentration corresponding to the sample in accordance with a following equation (2);