Near-infrared noninvasive spectroscopic determination of pH

• US 5,792,050 A
• Filed: 03/14/1996
• Issued: 08/11/1998
• Est. Priority Date: 07/06/1992
• Status: Expired due to Fees

• Current Assignee: Luminous Medical, Inc., Sandia Corporation (Martin Marietta Corporation), Rio Grande Medical Technologies Incorporated
• Original Assignee: Mark R. Robinson, Mary K. Alam
• Inventors: Robinson, Mark R., Alam, Mary K.
• Primary Examiner(s): Bahr, Jennifer
• Assistant Examiner(s): YARNELL, BRYAN KEITH
• Application Number:
  US08/615,762
• Time in Patent Office: 880 Days
• Field of Search: 128/633, 128/637, 128/664, 128/665, 356/39-41, 356/320, 356/432, 600/310, 600/322, 600/323, 600/326, 600/327, 600/341, 600/342
• US Class Current: 600/310
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/352 Detecting R peaks, e.g. for synchronising diagnostic apparatus; Estimating R-R interval
• CPC Class Codes: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6838 Clamps or clips

Abstract

Methods and apparatus for, preferably, determining noninvasively and in vitro pH in a human. The non-invasive method includes the steps of: generating light at three or more different wavelengths in the range of 1000 nm to 2500 nm; irradiating blood containing tissue; measuring the intensities of the wavelengths emerging from the blood containing tissue to obtain a set of at least three spectral intensities v. wavelengths; and determining the unknown values of pH. The determination of pH is made by using measured intensities at wavelengths that exhibit change in absorbance due to histidine titration. Histidine absorbance changes are due to titration by hydrogen ions. The determination of the unknown pH values is performed by at least one multivariate algorithm using two or more variables and at least one calibration model. The determined pH values are within the physiological ranges observed in blood containing tissue. The apparatus includes a tissue positioning device, a source, at least one detector, electronics, a microprocessor, memory, and apparatus for indicating the determined values.

Claims

1. A method of determining pH in blood containing tissue noninvasively, in vivo, and within and, physiological ranges observed in said blood containing tissue utilizing tissue spectra which spectra contains histidine information, said method comprising steps of:

a. generating light at three or more different wavelengths, said wavelengths being in the range of 1000 nm to 2500 nm;

b. irradiating said blood containing tissue with said wavelengths so that there is differential attenuation of at least some intensities of said wavelengths, said wavelength dependent differential attenuation being a function of said blood containing tissue, including histidine in said blood containing tissue;

c. measuring at least a portion of said intensities of said wavelengths emerging from said blood containing tissue to obtain a set of at least three spectral intensities v. wavelengths; and

d. estimating said value of said pH from said measured intensities by utilizing wavelength dependent differential attenuation derived from said histidine, said value being within said physiological ranges.

2. The method as set forth in claim 1, utilizing wavelength dependent differential attentuation derived from histidine, which exhibits a sensitivity due to changes in pH.

3. The method of claim 1, wherein said wavelengths used for said estimation of pH are those known to exhibit a differential attentuation due to hydrogen ions reacting with histidine.

4. The method as set forth in claim 3, wherein said wavelengths are in the range of 1000-1300 nm.

5. The method as set forth in claim 4, wherein said wavelengths include one or more of 1042, 1111 and 1163 nm.

6. The method as set forth in claim 3, wherein said wavelengths are in the range of 1300-2500 nm.

7. The method as set forth in claim 6, wherein said wavelengths are in the range of 1500-1820 nm.

8. The method as set forth in claim 7, wherein said wavelengths include 1600 nm.

9. The method as set forth in claim 6, wherein said wavelengths are in the range of 2040-2500 nm.

10. The method as set forth in claim 9, wherein said wavelengths include one or more of 2060-2115, 2160, 2225-2235 and 2360 nm.

11. A quantitative analysis instrument for noninvasive spectroscopic measurement of pH in human tissue, said instrument comprising:

a. a source of at least three different wavelengths of light, said wavelengths being in the range of 1000-2500 nm, at least some of said wavelengths having a wavelength dependent differential attenuation due to histidine;

b. optics for directing said wavelengths into said blood containing tissue;

c. at least one detector for measuring the intensity of at least a portion of said wavelengths emerging from said blood containing tissue that are differentially attenuated by histidine;

d. electronics for processing said measured intensities derived from said wavelengths that are differentially attenuated by histidine to estimate pH values in said tissue; and

e. means for indicating said estimated values of blood pH.

12. The analysis instrument of claim 11, wherein the said electronics utilizes a multivariate algorithm using at least two variables and a calibration model.

13. The analysis instrument of claim 12, wherein said calibration model is developed by an algorithm that is capable of using more spectral variables per sample than the number of calibration samples used to generate said model, and wherein each of said variables represents at least one spectral intensity.

14. The analysis instrument of claim 11, wherein said wavelengths are in the range of 1000-1300nm.

15. The analysis instrument of claim 14, wherein said wavelengths include one or more of 1042, 1111 and 1163 nm.

16. The analysis instrument of claim 11, wherein said wavelengths are in the range of 1300-2500nm.

17. The analysis instrument of claim 16, wherein said wavelengths are in the range of 1500-1820nm.

18. The analysis instrument of claim 17, wherein said wavelengths include 1600 nm.

19. The analysis instrument of claim 16, wherein said wavelengths are in the range of 2040-2500nm.

20. The analysis instrument of claim 19, wherein said wavelengths include one or more of 2060-2115, 2160, 2225-2235 and 2360 nm.

21. A method of determining pH in blood, within and physiological ranges observed in blood, utilizing spectra which spectra contains histidine information, said method comprising steps of:

a. generating light at three or more different wavelengths, said wavelengths being in the range of 1000 nm to 2500 nm;

b. irradiating said blood with said wavelengths so that there is differential attenuation of at least some intensities of said wavelength, said wavelength dependent differential attenuation being a function of said blood including histidine in said blood;

c. measuring at least a portion of said intensities of said wavelengths emerging from said blood to obtain a set of at least three spectral intensities v. wavelengths; and

d. estimating said value of said pH from said measured intensities by utilizing wavelength dependent differential attenuation derived from said histidine, said value being within said physiological ranges.

22. The method as set forth in claim 21, utilizing wavelength dependent differential attentuation derived from histidine, which exhibits a sensitivity due to changes in pH.

23. The method of claim 21, wherein said wavelengths used for said estimation of pH are those known to exhibit a differential attentuation due to hydrogen ions reacting with histidine.

24. The method as set forth in claim 23, wherein said wavelengths are in the range of 1000-1300 nm.

25. The method as set forth in claim 24, wherein said wavelengths include one or more of 1042, 1111 and 1163 nm.

26. The method as set forth in claim 23, wherein said wavelengths are in the range of 1300-2500 nm.

27. The method as set forth in claim 26, wherein said wavelengths are in the range of 1500-1820 nm.

28. The method as set forth in claim 27, wherein said wavelengths include 1600 nm.

29. The method as set forth in claim 23, wherein said wavelengths are in the range of 2040-2500 nm.

30. The method as set forth in claim 29, wherein said wavelengths include one or more of 2060-2115, 2160, 2225-2235 and 2360 nm.

31. A quantitative analysis instrument for spectroscopic measurement of pH in blood, said instrument comprising:

a. a source of at least three different wavelengths of light, said wavelengths being in the range of 1000-2500 nm, at least some of said wavelengths having a wavelength dependent differential attenuation due to histidine;

b. optics for directing said wavelengths of light into said blood;

c. at least one detector for measuring the intensity of at least a portion of said wavelengths of said light emerging from said blood that are differentially attenuate by histidine;

d. electronics for processing said measured intensities derived from said wavelengths that are differentially attenuate by said histidine to estimate pH values in said tissue; and

e. means for indicating said estimated values of blood pH.

32. The analysis instrument of claim 31, wherein the said electronics utilizes a multivariate algorithm using at least two variables and a calibration model.

33. The analysis instrument of claim 32, wherein said calibration model is developed by an algorithm that is capable of using more spectral variables per sample than the number of calibration samples used to generate said model, and wherein each of said variables represents at least one spectral intensity.

34. The analysis instrument of claim 31, wherein said wavelengths are in the range of 1000-1300nm.

35. The analysis instrument of claim 34, wherein said wavelengths include one ore more of 1042, 1111 and 1163 nm.

36. The analysis instrument of claim 31, wherein said wavelengths are in the range of 1300-2500nm.

37. The analysis instrument of claim 36, wherein said wavelengths are in the range of 1500-1820nm.

38. The analysis instrument of claim 37, wherein said wavelengths include 1600 nm.

39. The analysis instrument of claim 36, wherein said wavelengths are in the range of 2040-2500nm.

40. The analysis instrument of claim 39, wherein said wavelengths include one or more of 2060-2115, 2160, 2225-2235 and 2360 nm.