Apparatus and process for the non-invasive measurement of optically active compounds

• US 5,788,632 A
• Filed: 03/19/1996
• Issued: 08/04/1998
• Est. Priority Date: 03/19/1996
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Pezzaniti, J. Larry, Lindberg, John M.
• Primary Examiner(s): Bahr, Jennifer
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/618,654
• Time in Patent Office: 868 Days
• Field of Search: 128/633, 128/664, 128/665, 356/39, 356/364, 356/366, 356/368, 600/316, 600/318, 600/319, 600/322, 600/473, 600/476
• US Class Current: 600/316
• CPC Class Codes: A61B 5/14558 by polarisation
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence

Abstract

An apparatus and a process of determining the concentration of an optically active compound in a biological sample are provided. The process measures the entire polarization state of the sample and compares the measured polarization state of the sample to the polarization state of a sample having a known concentration of that compound. The polarization state of the sample is measured after manipulating the polarization state of light entering and leaving the sample and detecting the light leaving the sample. The apparatus contains a source of light, a sample holder for holding the biological sample, a detector, a first polarization manipulator between the light source and the sample holder, a second polarization manipulator between the sample holder and the detector and an analyzer to correlate detected signals with concentration of the optically active compound.

Claims

1. An apparatus for the non-invasive measurement of an optically active component in a biological sample comprising:

a) a source of unpolarized light;

b) a first means for manipulating the polarization state of light in optical alignment with the light source;

c) a sample holder adapted to hold the biological sample in optical alignment with the first means for manipulating light to allow light to pass through the sample, wherein the first means for manipulating the polarization state of light includes a first means for polarizing light optically aligned with the light source and a first means for variably retarding light optically aligned with the first means for polarizing light and the sample holder, wherein the first means for polarizing light includes a first polarizer and the first means for variably retarding light includes a first variable retarder, wherein the first variable retarder contains a pair of variable retarders with the fast axis of the first retarder of the pair being oriented about 45°

to the fast axis of the second retarder of the pair;

d) a second means for manipulating the polarization state of light in optical alignment with the sample holder to receive light passing through the sample;

e) means for detecting light in optical alignment with the second means for manipulating the polarization state of light; and

f) means for analyzing an electric signal from the means for detecting light to correlate the electric signal with a concentration of the optically active compound.

2. The apparatus of claim 1 wherein the first variable retarder is a rotating retarder.

3. The apparatus of claim 1 wherein the second means for manipulating the polarization state of light includes a second means for variably retarding light optically aligned with the sample holder and a second means for polarizing light optically aligned with the second means for variably retarding light and the means for detecting light.

4. The apparatus of claim 3 wherein the second means for variably retarding light includes a second variable retarder and the second means for polarizing light includes a second polarizer.

5. The apparatus of claim 4 wherein the second variable retarder includes a rotating retarder.

6. The apparatus of claim 5 wherein the first and second variable retarders are rotating retarders.

7. The apparatus of claim 6 further comprising a means for regulating the rotation of the rotating retarders operatively associated with the rotating retarders.

8. The apparatus of claim 7 wherein the means for regulating the rotation of the rotating retarders includes means for rotating the rotating retarders simultaneously at different angular frequencies.

9. The apparatus of claim 5 wherein both the first and second variable retarders consist of a pair of variable retarders with the fast axis of the first retarder of the pair oriented about 45°

to the fast axis of the second retarder of the pair.

10. The apparatus of claim 9 wherein a means for regulating retardance of the first and second variable retarders is operatively associated with the first and second variable retarders.

11. The apparatus of claim 10 wherein the means for regulating retardance of the first and second variable retarders includes a means for changing the retardance simultaneously at different frequencies.

12. The apparatus of claim 4 wherein the second means for variably retarding light contains a pair of variable retarders with the fast axis of the first retarder of the pair oriented about 45°

to the fast axis of the second retarder of the pair.

13. The apparatus of claim 1 wherein the means for analyzing includes a data processor operatively associated with the means for detecting and a controller operatively associated with the first and second means for manipulating polarization states.

14. The apparatus of claim 1 further comprising first means for focusing light positioned between the light source and the first means for manipulating the polarization state of light and second means for focusing light positioned between the second means for manipulating the polarization state of light and the means for detecting light.

15. The apparatus of claim 14 further comprising means for splitting light optically aligned with the second means for focusing light and a means for dispersing light optically aligned and positioned between the means for splitting light and the means for detecting light.

16. The apparatus of claim 15 wherein the means for detecting light includes a plurality of linear array detectors.

17. The apparatus of claim 1 wherein the light source includes a plurality of discrete light sources, each of which emits light at a particular wavelength.

18. The apparatus of claim 17 further comprising a plurality of means for filtering light, each of which is optically aligned with one of said discrete light sources.

19. The apparatus of claim 18 further comprising a plurality of means for reflecting light, each of which is optically aligned with one of the means for filtering light and positioned to direct light from the filtering means to the first means for manipulating the polarization state of light.

20. A process of determining the concentration of an optically active compound in a biological sample comprising the steps of:

measuring the entire polarization state of the sample, and

comparing the measured polarization state of the sample to the polarization state of a sample having a known concentration of that compound, wherein the polarization state of the sample is measured after the polarization state of light entering the sample is manipulated and the polarization state of light leaving the sample is manipulated and the light leaving the sample is detected.

21. The process of claim 20 wherein the polarization state of light entering the sample is manipulated by sequentially passing light through a first means for polarizing light and a first means for variably retarding light before entering the sample.

22. The process of claim 21 wherein the polarization state of the light leaving the sample is manipulated by sequentially passing the light through a second means for variably retarding light and a second means for polarizing light.

23. The process of claim 22 wherein the frequency, phase, and intensity of the light leaving the second means for polarizing light is detected and an electric signal is generated.

24. The process of claim 23 wherein the electric signal is correlated with the concentration of the optically active compound in the sample.

25. The process of claim 20 wherein the optically active compound is glucose.

26. A noninvasive process of determining glucose concentration in a biological sample comprising the steps of:

a) sequentially passing a light beam through a first polarizer and a first variable retarder, wherein the first variable retarder contains a pair of variable retarders with the fast axis of the first retarder of the pair being oriented about 45°

to the fast axis of the second retarder of the pair;

b) directing the light beam through the sample contained in a sample holder;

c) sequentially passing light from the sample through a second variable retarder and a second polarizer;

d) detecting the light from the second polarizer with a detector; and

e) processing an electric signal generated by the detector with an analyzer to a signal indicative of the concentration of glucose in the sample.

27. The process of claim 26 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

28. A polarization generator for introducing polarization states into a sample, comprising:

a linear polarizer,

a first variable retarder having its fast axis oriented at 45°

relative to the transmission axis of the polarizer,

c) a second variable retarder in optical alignment with the first variable retarder and having the fast axis of the second retarder oriented parallel to the transmission axis of the linear polarizer.

29. A process for measuring the Mueller matrix of a sample comprising the steps of optically aligning a sample with an optical beam generated by the polarization generator of claim 28, detecting the light emerging from the sample, and processing an electric signal generated by the detected light with an analyzer to indicate the concentration of an optically active compound in the sample.

30. The process of claim 29 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

32. A process for measuring the Mueller matrix of a sample, comprising the steps of:

a) transmitting light through the polarization generator of claim 28, said polarization generator aligned with the sample,

b) transmitting said light transmitted through the polarization generator through the sample, and

c) transmitting the light transmitted through the sample through the polarization analyzer of claim 31, the polarization analyzer being in optical alignment with the light transmitted through the sample and parallel to the light transmitted through the polarization generator.

33. The process of claim 32, wherein multiple wavelengths are used.

34. The process of claim 32, further including the step of reducing the Mueller matrix of the sample, wherein the step of reducing is selected from the group consisting of horizontal linear diattenuation, 45°

linear diattenuation, circular diattenuation, horizontal linear retardance, 45°

linear retardance, circular retardance, or depolarization.

35. The process of claim 34 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

36. The process of claim 34, wherein the step of reducing is selected from the group consisting of horizontal linear diattenuation, 45°

linear diattenuation, and circular diattenuation.

37. The process of claim 34, wherein the step of reducing is selected from the group consisting of horizontal linear retardance, 45°

linear retardance, and circular retardance.

38. The process of claim 34, wherein the step of reducing is depolarization.

39. The process of claim 32 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

40. A process for measuring circular retardance of a sample, comprising the steps of:

a) transmitting light through the polarization generator of claim 28, said polarization generator aligned with the sample,

b) transmitting said light transmitted through the polarization generator through the sample, and

c) transmitting the light transmitted through the sample through the polarization analyzer of claim 31, the polarization analyzer being in optical alignment with the light transmitted through the sample and parallel to the light transmitted through the polarization generator, said polarization analyzer having variable retarders removed therefrom.

41. The process of claim 40 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

42. The process of claim 40, wherein multiple wavelengths are used.

31. A polarization analyzer for analysis of polarization sates of a sample, comprising:

a) a first variable retarder optically aligned with a sample holder,

b) a second variable retarder having its fast axis oriented at 45°

relative to the fast axis of the first linear retarder, optically aligned with the sample holder,

c) a linear polarizer having its transmission axis oriented parallel to the fast axis of the first variable retarder.

43. A process for measuring circular dichroism of a sample, comprising the steps of:

a) transmitting light through the polarization generator of claim 32, said polarization generator aligned with the sample,

b) transmitting said light transmitted through the polarization generator through the sample, and

c) transmitting the light transmitted through the sample through the polarization analyzer of claim 31, the polarization analyzer being in optical alignment with the light transmitted through the sample and parallel to the light transmitted through the polarization generator, said polarizer preceding said detector being removed.

44. The process of claim 43 wherein the sample is a finger, earlobe, eye, eyelid, or aqueous humor of an eye.

45. The process of claim 43, wherein multiple wavelengths are used.