Clinical analyte determination by infrared spectroscopy

• US 6,285,448 B1
• Filed: 11/05/1997
• Issued: 09/04/2001
• Est. Priority Date: 05/05/1997
• Status: Expired due to Term

• Current Assignee: Kuenstner J. Todd
• Original Assignee: Kuenstner J. Todd
• Inventors: Kuenstner, J. Todd
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Smith, Zandra V.
• Application Number:
  US08/965,071
• Time in Patent Office: 1,399 Days
• Field of Search: 356/39, 356/40, 356/41
• US Class Current: 356/39
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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

Abstract

The present invention comprises methods for minimally invasive and noninvasive analyte determination using infrared spectroscopy. A minimally invasive in vitro method comprises obtaining a volume of a fluid sample. A minimally invasive manner of obtaining the sample includes using a laser to form a micropore on a user'"'"'s skin. The sample is placed on a plane of an optically clear window, such as by pressing the window against the micropore. Infrared light is directed through the window and the sample at an angle such that the light path is approximately vertical. The resulting spectrum is measured and subjected to multivariate analysis to determine the presence of at least one analyte. A noninvasive in vivo method comprises obtaining a spectral measurement of a sample in conjunction with the arterial pulse measurement. A difference spectrum is determined by subtracting the arterial pulse trough measurement from the peak measurement. The difference spectrum is normalized by dividing by the area of the absolute value of the derivative spectrum. The presence of at least one analyte is determined by applying multivariate analysis to the normalized spectrum.

Claims

1. An in-vitro method for determining the concentration of one or more clinical analytes comprising the steps of:

(a) obtaining a volume of a fluid sample comprising interstitial fluid;

(b) contacting a portion of said sample on a plane of an optically clear first window;

(c) placing a second optically clear window in contact with the first window to thereby sandwich the sample between the windows;

(d) shining a known wavelength of light from the mid-infrared spectrum for an uncontrolled path length through said windows and said sample in a path perpendicular to said plane;

(e) measuring a spectrophotometric property of said light; and

(f) performing a quantitative mathematical analysis of said spectrophotometric property to determine the concentration of at least one analyte, wherein the fluid sample is obtained by creating a micropore on the surface of the skin of a patient, wherein said micropore at least partially fills with interstitial fluid and pressing said first window against the micropore to collect a volume of said interstitial fluid.

2. The method of claim 1, wherein the step of contacting said sample on a first window further comprises the step of contacting said window with a fluid collection area.

3. An in vitro method of clinical analyte determination as recited in claim 1, wherein the step of contacting said sample on a first window further comprises the step of contacting said window whit said micropore.

4. The method of claim 1, wherein the first window comprises a barium fluoride window.

5. The method of claim 1, wherein said sample is placed on a polyethylene card sandwiched between two barium fluoride windows.

6. The method of claim 1, wherein the step of contacting said sample on a first window further comprises the step of providing a second window and opposing said second window against said sample and said first window.

7. The method of claim 1, wherein the known wavelength is in the range of about 1185 to 960 cm⁻

1.

8. The method of claim 1, wherein the step of performing a mathematical analysis further comprises performing a partial least squares analysis.

9. The method of claim 1, wherein the step of performing a mathematical analysis further comprises the steps of:

(a) normalizing said spectrum; and

(b) performing a multivariate analysis.

10. An in vitro method of clinical analyte determination as recited in claim 9, wherein the step of normalizing said spectrum further comprises dividing said spectrum by the area of the absolute value of the derivative spectrum.

11. The method of claim 1, wherein the step of performing a mathematical analysis further comprises determining the presence of glucose.

12. The method of claim 1, wherein the fluid sample comprises whole blood and the step of performing a mathematical analysis further comprises determining the presence of hemoglobin.

13. The method of claim 1, wherein the step of performing a mathematical analysis further comprising determining the presence of urea.

14. The method of claim 1, wherein the step of performing a mathematical analysis further comprising determining the presence of cholesterol.

15. The method of claim 1, wherein the step of performing a mathematical analysis further comprising determining the presence of any combination of glucose, urea and cholesterol.

16. An apparatus for clinical analyte determination, comprising:

means for obtaining a volume of a fluid sample, wherein at least a portion of said sample is disposed on a plane of an optically clear window;

means for shining a known wavelength of light from the mid-infrared spectrum through said window and said sample in a path perpendicular to said plane;

means for measuring a spectrum produced by the transmittance of said light; and

means for performing a mathematical analysis of said spectrum to determine the presence of an analyte,

wherein the means for obtaining a volume of a fluid sample comprise means for creating a micropore on the surface of the skin of a patient that will at least partially fill with interstitial fluid and a first window for pressing against the micropore to collect a volume of said interstitial fluid.