Non-invasive detection of analytes in a complex matrix

• US 7,174,198 B2
• Filed: 12/23/2003
• Issued: 02/06/2007
• Est. Priority Date: 12/27/2002
• Status: Expired due to Fees

• Current Assignee: Igor Trofimov, Stephen A. Lyon
• Original Assignee: Igor Trofimov, Stephen A. Lyon
• Inventors: Trofimov, Igor, Lyon, Stephen A.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/745,092
• Publication Number:
  US 20040135085A1
• Time in Patent Office: 1,141 Days
• Field of Search: 600309-310, 600/316, 600/322, 600/336, 356 39- 40
• US Class Current: 600/322
• 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: G01J 3/4338 Frequency modulated spectrometry
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence

Abstract

A system and method for determining the concentration of analytes of interest in complex matrices is provided. According to one aspect of the present invention, near-infrared analytical radiation is generally directed onto a portion of a specimen containing the analyte of interest. A wavelength of the analytical radiation is scanned over the specimen over a broad range of frequencies and over a short duration of diagnostic time. A spectrum of radiation is transmitted through, reflected from or scattered from the specimen and collected by a detector. The concentration of the analyte of interest in the specimen is determined by the radiation collected by the detector.

Claims

1. A system for detecting an analyte in a specimen characterized by a given cardiac period;

the system comprising;

a radiation source configured to generate analytical radiation such that a wavelength of said analytical radiation scans an analytical spectral range over a diagnostic time period, wherein

said analyte is characterized by an absorption spectrum within said analytical spectral range and

a duration of said diagnostic time period is a fraction of said cardiac period;

a detector configured to receive said analytical radiation and generate a signal indicative of attenuation of said analytical radiation over at least a portion of said spectral range, wherein said radiation source and said detector are configured such that an intensity of said analytical radiation received by said detector is subject to attenuation by said analyte within at least a portion of said analytical spectral range; and

a processor configured to receive said attenuation signal until a desired signal-to-noise ratio associated with said attenuation signal is established by said processor.

2. The system of claim 1, wherein the duration of said cardiac period ranges from about 0.3 to about 2 seconds.

3. The system of claim 2, wherein the duration of said diagnostic time period is less than one half of said cardiac period.

4. The system of claim 2, wherein the duration of said diagnostic time period is less than about 5% of said cardiac period.

5. A system for detecting an analyte in a specimen;

the system comprising;

a radiation source configured to generate a single beam of analytical radiation and to scan a wavelength of said single beam of analytical radiation over an analytical spectral range, wherein said analyte is characterized by an absorption spectrum within said analytical spectral range; and

a detector configured to receive said single beam of analytical radiation and from said received single beam of analytical radiation generate a signal indicative of attenuation of said single beam of analytical radiation over at least a portion of said spectral range, wherein said source and said detector are configured such that an intensity of said analytical radiation received by said detector is subject to attenuation by said analyte within at least a portion of said analytical spectral range; and

a processor configured to receive said attenuation signal until a desired signal-to-noise ratio associated with said attenuation signal is established by said processor.

6. The system of claim 5, wherein said analytical spectral range lies between about 900 nm and about 2700 nm.

7. A system for detecting an analyte-of-interest in a specimen;

the system comprising a radiation source, a detector, and a processor, wherein;

said radiation source is configured to

generate analytical radiation characterized by a spectral line width less than about 20 nm over an analytical spectral range from about 900 nm to about 2700 nm,

control the spectral width of said analytical spectral range so as to enable discrimination between said analyte-of-interest and other analytes in said specimen,

scan a wavelength of said analytical radiation over said controlled spectral width;

said detector is configured to receive said analytical radiation and generate a signal indicative of attenuation of said analytical radiation over at least a portion of said spectral range;

said source and said detector are configured such that an intensity of said analytical radiation received by said detector is subject to attenuation by said analyte within at least a portion of said analytical spectral range; and

said processor is configured to receive said attenuation signal until a desired signal-to-noise ratio associated with said attenuation signal is established by said processor.

8. The system of claim 7, wherein said radiation source comprises one of a laser, a light emitting diode, an optical parametric oscillator, and combinations thereof.

9. The system of claim 7, wherein said radiation source comprises one of a semiconductor laser diode, a color center laser, a fiber laser, a solid state laser, a quantum cascade laser and combinations thereof.

10. The system of claim 7, wherein said radiation source comprises a single tunable laser.

11. The system of claim 7, wherein said radiation source comprises an external cavity laser.

12. The system of claim 11, wherein said external cavity laser comprises one of a Cr doped ZnSe, ZnS and CdS laser.

13. The system of claim 11, wherein said external cavity laser defines a Littman-Metcalf configuration.

14. The system of claim 11, wherein said external cavity laser defines a Littrow configuration.

15. The system of claim 7, wherein said analyte is characterized by a given cardiac period of said specimen.

16. The system of claim 15, wherein said radiation source is further configured to generate said analytical radiation over a diagnostic time period.

17. The system of claim 16, wherein said diagnostic time period is no greater than a duration of said cardiac period.

18. The system of claim 17, wherein the duration of said cardiac period ranges from about 0.3 to about 2 seconds.

19. The system of claim 17, wherein the duration of said diagnostic time period is less than one half of said cardiac period.

20. The system of claim 16, wherein the duration of said diagnostic time period is less than about 5% of said cardiac period.

21. The system of claim 7, wherein said analytical radiation is characterized by a spectral line width of about 1 nm.

22. The system of claim 7, wherein a width of said analytical spectral range is between about 50 nm and 400 nm.

23. The system of claim 7, wherein said analytical spectral range lies between about 2050 nm and about 2400 nm.

24. The system of claim 7, wherein said detector is configured to receive analytical radiation reflected from said specimen.

25. The system of claim 7, wherein said detector is configured to receive analytical radiation scattered from said specimen.

26. The system of claim 7, wherein said detector is configured to receive analytical radiation transmitted through said specimen.

27. The system of claim 7, further comprising:

an analog-to-digital converter configured to convert said signal indicative of attenuation of said analytical radiation into a digital signal.

28. The system of claim 7, wherein the radiation source and the detector are portable.

29. The system of claim 7, further comprising:

a processor configured to receive said signal indicative of attenuation of said analytical radiation from said detector.

30. The system of claim 29, wherein the processor is further configured to determine an absorption spectrum over the analytical spectral range.

31. The system of claim 30, wherein the processor is further configured to correlate the absorption spectrum with an analyte of interest in said specimen.

32. The system of claim 31, wherein the processor is further configured to determine a concentration of said analyte of interest.

33. The system of claim 32, further comprising:

an analyte control device to receive said concentration of said analyte of interest as input.

34. The system of claim 33, wherein the analyte control device is

configured to adjust levels of analyte of interest concentration in said specimen as function of the inputted concentration of said analyte of interest.

35. The system of claim 33, wherein the analyte control device comprises an insulin pump.

36. The system of claim 7, wherein said radiation source is configured to maintain said radiation source fixed at a single wavelength until said signal-to-noise ratio exceeds a given value.

37. The system of claim 36, wherein said radiation source is configured to step to another wavelength in said analytical spectral range after achieving said desired signal-to-noise ratio.

38. The system of claim 7, wherein said radiation source is configured to repeat said scan over said analytical spectral range until said signal-to-noise ratio exceeds a given value.

39. The system of claim 7, wherein the analyte comprises one of glucose, urea, cholesterol, ketone, creatinine, bilirubin and proteins.

40. The system of claim 7, wherein the analyte comprises one of a contaminant and a pollutant.

41. The system of claim 7, wherein said specimen is a biological specimen.

42. The system of claim 41, wherein said analytical radiation received by said detector is reflected or scattered from said biological specimen over at least a portion of said spectral range.

43. The system of claim 41, wherein said analyte-of-interest in said biological specimen is in the proximity of a nail plate of a digit of said biological specimen.

44. The system of claim 7, wherein said processor establishes said desired signal-to-noise ratio by fixing said analytical radiation at a single wavelength, accumulating and averaging signals at said single wavelength until reaching said desired signal-to-noise ratio, stepping to a next wavelength, accumulating and averaging signals at said next wavelength until reaching said desired signal-to-noise ratio, repeating stepping, accumulating and averaging over all wavelengths of said spectral range within a fraction of a cardiac period of said specimen.

45. The system of claim 7, wherein said radiation source repeats said scan over said analytical spectral range within a fraction of a predetermined diagnostic time period until said signal-to-noise ratio exceeds a given value.

46. The system of claim 7, wherein said radiation source scans a single wavelength within a fraction of a predetermined diagnostic time period until said signal-to-noise ratio exceeds a given value and steps to another wavelength in said analytical spectral range after said signal-to-noise ratio is established.