System for improving the sensitivity and stability of optical polarimetric measurements

• US 6,370,407 B1
• Filed: 06/12/2000
• Issued: 04/09/2002
• Est. Priority Date: 07/27/1999
• Status: Expired due to Term

• Current Assignee: Alan J. Leszinske
• Original Assignee: TecMed, Incorporated
• Inventors: Leszinske, Alan J., Kroeger, James K.
• Primary Examiner(s): Winakur, Eric F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US09/591,955
• Time in Patent Office: 666 Days
• Field of Search: 600/318-319, 600/309-310, 600/331, 600/322, 600/326, 600/316, 356/39-42, 356/364
• US Class Current: 600/319
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 5/14558 by polarisation
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence

Abstract

A polarimeter adapted for measurement of the concentration of glucose in a sample includes a laser beam passing through a first polarizer and an optical modulator and split into a measurement beam passing through a FIRST ANALYZER to a first detector coupled to a first amplifier and a reference beam passing through a SECOND ANALYZER to a second detector coupled to a second amplifier. Identical multiple filtering and summing operations are performed on outputs of the first and second amplifiers to produce a first Ψ²/2 signal and a first 2βΨ signal in response to the measurement beam and a second Ψ²/2 signal and a second 2βΨ signal in response to the reference beam. The measurement beam is stabilized by comparing the second Ψ²/2 signal to a first reference signal to produce a first error signal and comparing the second 2βΨ signal to a second reference signal to produce a second error signal. The first error signal is multiplied by a modulation signal to produce a modulation feedback signal and adding it to the second error signal to produce a combined modulation and zeroing feedback signal which drives the optical modulator so as to minimize the first and second error signals. First and second values of β are computed from the first Ψ²/2 signal and the first 2βΨ signal without and with the sample in the path of the measurement beam, and the difference is converted to a value of glucose concentration in the sample.

Claims

1. A method for polarimetric measurement of optical rotation of light caused by a concentration of a substance contained in a sample, comprising:

(a) providing a laser beam passing through a polarizer and an optical modulator and split into a measurement beam and a reference beam, analyzing the measurement beam and directing it onto a first detector coupled to a first amplifier, and analyzing the reference beam and directing it onto a second detector coupled to a second amplifier;

(b) performing identical filtering at integral multiples of a modulation frequency, and performing multiplication and algebraic summing operations on outputs of the first and second amplifiers to produce a first Ψ

²/2 signal and a first 2β

Ψ

signal in response to the measurement beam and a second Ψ

²/2 signal and a second 2β

Ψ

signal in response to the reference beam, Ψ

representing a modulation level of light emanating from the optical modulator, and β

representing optical rotation from extinction of the measurement beam or reference beam;

(c) stabilizing the measurement beam by

i. comparing the second Ψ

²/2 signal to a first reference signal to produce a first error signal,

ii. comparing the second 2β

Ψ

signal to a second reference signal to produce a second error signal,

iii. multiplying the first error signal by a modulation signal to produce a modulation feedback signal and adding it to the second error signal to produce a combined modulation and zeroing feedback signal, and

iv. driving the optical modulator in response to the combined modulation and zeroing feedback signal to minimize the first and second error signals; and

(d) computing a first value of β

from the first Ψ

²/2 signal and the first 2β

Ψ

signal with no sample in a path of the measurement beam and a second value of β

from the first Ψ

²/2 signal and the first 2β

Ψ

signal with the sample in the path of the measurement beam, and computing the difference between the first and second values of β

.

2. The method of claim 1 wherein step (a) includes directing the measurement beam to an analyzer by means of a glass guide, and providing a compensation coil around the glass guide, measuring the temperature of the glass guide, and controlling a current in the compensation coil to compensate the temperature coefficient of the Verdet constant of the glass guide.

3. The method of claim 1 wherein each of the first and second 2β

Ψ

signals has a value according to the expression

4. The method of claim 3 wherein each of the first and second Ψ

²/2 signals has a value according to the expression

5. The method of claim 4 wherein the magnitude of the modulation level of light Ψ

corresponds to a modulation angle δ

substantially greater than 45 degrees, and wherein Ψ

cos(ω

t) is the electrical signal applied to the optical modulator to produce the modulation angle δ

of the polarized light.

6. The method of claim 4 wherein the magnitude of the modulation level of light Ψ

corresponds to a modulation angle δ

in the range of approximately 30 degrees to 75 degrees, and wherein Ψ

cos(ω

t) is the electrical signal applied to the optical modulator to produce the modulation angle δ

of the polarized light.

7. The method of claim 1 wherein the filtering at integral multiples of the modulation frequency in step (b) is performed by fast Fourier transforms to be used in the multiplication and algebraic summing operations.

8. The method of claim 7 including performing a coherent averaging operation on the fast Fourier transforms to improve the signal-to-noise ratio of the polarimetric measurement.

9. A method for polarimetric measurement of the concentration of a substance contained in a sample, comprising:

(a) providing a laser beam passing through a polarizer and an optical modulator and split into a measurement beam and a reference beam, analyzing the measurement beam, and directing it onto a first detector coupled to a first amplifier, and analyzing the reference beam and directing it onto a second detector coupled to a second amplifier;

(b) performing identical filtering at integral multiples of a modulation frequency, and performing multiplication and algebraic summing operations on outputs of the first and second amplifiers to produce a first Ψ

²/2 signal and a first 2β

Ψ

signal in response to the measurement beam and a second Ψ

²/2 signal and a second 2β

Ψ

signal in response to the reference beam, β

representing a modulation level of light emanating from the optical modulator, and Ψ

representing optical rotation from extinction of the measurement beam or reference beam;

(c) stabilizing the measurement beam by

i. comparing the second Ψ

²/2 signal to a first reference signal to produce a first error signal,

ii. comparing the second 2β

Ψ

signal to a second reference signal to produce a second error signal,

iii. multiplying the first error signal by a modulation signal to produce a modulation feedback signal and adding it to the second error signal to produce a combined modulation and zeroing feedback signal, and

iv. driving the optical modulator in response to the combined modulation and zeroing feedback signal to minimize the first and second error signals; and

(d) computing a first value of β

from the first 2β

Ψ

signal with no sample in a path of the measurement beam and a second value of β

from the first 2β

Ψ

signal with the sample in the path of the measurement beam, and converting the difference between the first and second values of β

to a value of concentration of the substance in the sample.

10. The method of claim 9 wherein each of the first and second 2β

Ψ

signals has a value according to the expression

11. The method of claim 10 wherein the magnitude of the modulation-level of light Ψ

corresponds to a modulation angle δ

substantially greater than 45 degrees, and wherein Ψ

cos(ω

t) is the electrical signal applied to the optical modulator to produce the modulation angle δ

of the polarized light.

12. The method of claim 10 wherein the magnitude of the modulation level of light Ψ

corresponds to a modulation angle δ

in the range of approximately 30 degrees to 75 degrees, and wherein Ψ

cos(ω

t) is the electrical signal applied to the optical modulator to produce the modulation angle δ

of the polarized light.

13. The method of claim 9 wherein the filtering at integral multiples of the modulation frequency in step (b) is performed by fast Fourier transforms to be used in the multiplication and algebraic summing operations.

14. The method of claim 13 including performing a coherent averaging operation on the fast Fourier transforms to improve the signal-to-noise ratio of the polarimetric measurement.

15. The method of claim 9 wherein step (a) includes directing the measurement beam to an analyzer by means of a first glass guide.

16. The method of claim 15 including providing a compensation coil around the first glass guide, measuring the temperature of the first glass guide, and controlling a current in the compensation coil to compensate for the temperature coefficient of the Verdet constant of the first glass guide.

17. The method of claim 15 including introducing the sample in the path of the measurement beam ahead of the first glass guide.

18. The method of claim 17 wherein the sample is an ear lobe, the method including placing a portion of the first glass guide behind the ear lobe.

19. The method of claim 9 wherein the substance is glucose, and the sample is human tissue.

20. The method of claim 19 wherein step (d) includes using a stored look-up table or an algorithm to convert the difference between the first and second values of β

to a value of glucose concentration in the sample.

21. The method of claim 9 including converting analog output signals produced by the first amplifier to digital measurement channel signals, and converting analog output signals produced by the second amplifier to digital reference channel signals.

22. The method of claim 21 including performing one of steps (b) and (c) in a digital signal processor operating in response to the digital measurement channel signals and the digital reference channel signals.

23. The method of claim 15 including zeroing a measurement channel including the measurement beam by driving the measurement beam to extinction by means of a compensation coil around the first glass guide with no sample in the measurement channel.

24. A system for polarimetric measurement of the concentration of glucose in a sample, comprising:

(a) a polarizer;

(b) an optical modulator;

(c) a laser producing a laser beam passing through the polarizer and then passing through the optical modulator;

(d) a beam splitter splitting the beam emanating from the optical modulator into a measurement beam and a reference beam;

(e) means for analyzing the measurement beam and the reference beam;

(f) a first detector detecting the analyzed measurement beam, and a second detector detecting the analyzed reference beam;

(g) a first amplifier amplifying an output of the first detector, and a second amplifier amplifying an output of the second detector;

(h) means for performing identical filtering at integral multiples of a modulation frequency, and performing multiplication and algebraic summing operations on outputs of the first and second amplifiers to produce a first Ψ

²/2 signal and a first 2β

Ψ

signal in response to the measurement beam and a second Ψ

²/2 signal and a second 2β

Ψ

signal in response to the reference beam, Ψ

representing a modulation level of light emanating from the optical modulator, and β

representing optical rotation from extinction of the measurement beam or reference beam;

(i) means for stabilizing the measurement beam by

i. comparing the second Ψ

²/2 signal to a first reference signal to produce a first error signal,

ii. comparing the second 2β

Ψ

signal to a second reference signal to produce a second error signal,

iii. multiplying the first error signal by a modulation signal to produce modulation feedback signal and adding it to the second error signal to produce a combined modulation and zeroing feedback signal, and

iv. driving the optical modulator in response to the combined modulation and zeroing feedback signal to minimize the first and second error signals; and

(j) means for computing a first value of β

from the first 2β

Ψ

signal with no sample in the path of the measurement beam and a second value of β

from the first 2β

Ψ

signal with the sample in the path of the measurement beam, and converting the difference between the first and second values of β

to a value of glucose concentration in the sample.

25. A system for polarimetric measurement of the concentration of an optically active substance in a sample, comprising:

(a) a polarizer;

(b) an optical modulator;

(c) a laser producing a laser beam passing through the polarizer and then through the optical modulator;

(d) a splitter splitting the beam emanating from the optical modulator into a measurement beam and a reference beam;

(e) a first analyzer in the path of the measurement beam and a second analyzer in the path of the reference beam;

(f) a first detector detecting the analyzed measurement beam, and a second detector detecting the analyzed reference beam;

(g) a first amplifier amplifying an output of the first detector, and a second amplifier amplifying an output of the second detector; and

(h) a digital signal processor adapted to

i. perform identical filtering at integral multiples of a modulation frequency, and performing multiplication and algebraic summing operations on digital representations of outputs of the first and second amplifiers to produce a first Ψ

²/2 signal and a first 2β

Ψ

signal in response to the measurement beam and a second Ψ

²/2 signal and a second 2β

Ψ

signal in response to the reference beam, Ψ

representing a modulation level of light emanating from the optical modulator, and β

representing optical rotation from extinction of the measurement beam or reference beam,

ii. stabilize the measurement beam by comparing the second Ψ

²/2 signal to a first reference signal to produce a first error signal, comparing the second 2β

Ψ

signal to a second reference signal to produce a second error signal, multiplying the first error signal by a modulation signal to produce a modulation feedback signal and adding it to the second error signal to produce a combined modulation and zeroing feedback signal, and driving the optical modulator in response to the combined modulation and zeroing feedback signal to minimize the first and second error signals, and

iii. compute a first value of β

from the first 2β

Ψ

signal with no sample in the path of the measurement beam and a second value of β

from the first 2β

Ψ

signal with the sample in the path of the measurement beam, and converting the difference between the first and second values of β

to a value of glucose concentration in the sample.

26. The system of claim 25 wherein the substance is glucose, and the sample is human tissue.

27. The system of claim 25 including a first analog-to-digital converter having an input coupled to the output of the first amplifier and an output coupled to a digital input of the digital signal processor, and a second analog-to-digital converter having an input coupled to the output of the second amplifier and an output coupled to the digital input of the digital signal processor.

28. The system of claim 25 including a Faraday glass guide guiding the measurement beam to the first analyzer with a compensation coil around the glass guide, a temperature sensor adapted for measuring the temperature of the glass guide, an analog-to-digital converter coupled between the temperature sensor and the digital signal processor and adapted to convert an output signal produced by the temperature sensor to a digital signal, the digital signal processor compensating the first and second values of β

for the temperature coefficient of the V erdet constant of the glass guide during computing of the first and second values of β

.

29. The system of claim 28 wherein the system is packaged in a housing including a first section containing a portion of the glass guide, the first section bounding a first side of a recess for receiving an earlobe, finger or the like as the sample, the glass guide guiding the measurement beam through the sample in the recess.

30. The system of claim 29 wherein the housing includes a moveable second section bounding a second side of the recess, to provide a measurement of the width of the sample.

31. The system of claim 30 including a transducer coupled to the moveable second section and adapted to provide a signal representative of the width of the sample to the digital signal processor for use in computing the second value of β

.