Glucose monitoring apparatus and method using laser-induced emission spectroscopy

• US 6,232,609 B1
• Filed: 12/01/1995
• Issued: 05/15/2001
• Est. Priority Date: 12/01/1995
• Status: Expired due to Term

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Snyder, Wendy J., Grundfest, Warren S.
• Primary Examiner(s): Westin, Edward P.
• Assistant Examiner(s): HANIG, RICHARD E
• Application Number:
  US08/566,313
• Time in Patent Office: 1,992 Days
• Field of Search: 250/461.1, 250/458.1, 250/459.1
• US Class Current: 250/461.1
• 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

Abstract

A glucose monitor, and related method, determines the concentration of glucose in a sample with water, using a predictive regression model. The glucose monitor illuminates the sample with ultraviolet excitation light that induces the water and any glucose present in the sample to emit return light that includes raman scattered light and glucose emission or fluorescence light. The return light is monitored and processed using a predictive regression model to determine the concentration of glucose in the sample. The predictive regression model accounts for nonlinearities between the glucose concentration and intensity of return light within different wavelength bands at a predetermined excitation light energy or the intensity of return light within a predetermined wavelength band at different excitation energy levels. A fiber-optic waveguide is used to guide the excitation light from a laser excitation source to the sample and the return light from the sample to a sensor.

Claims

1. Apparatus for determining the concentration of glucose in a sample that includes water, comprising:

a light source that emits ultraviolet excitation light of at least one predetermined energy level, that is directed at a sample to produce return light from the sample, such return light including induced emission of light produced as a result of interactions between the excitation light and any glucose with water present in the sample;

a sensor that monitors the return light and generates at least three electrical signals indicative of the intensity of return light associated with glucose concentration distinguishing characteristics of the emission light, the at least three electrical signals including at least two electrical signals indicative of the intensity of return light at a respective number of wavelengths within a predetermined, narrow wavelength band corresponding to at least one characteristic narrow spectral peak, and a third electrical signal indicative of the intensity of return light within a predetermined, narrow wavelength band outside of the narrow spectral peak; and

a processor that processes the electrical signals, using a predictive model, to determine the concentration of glucose in the sample.

2. Apparatus for determining the concentration of glucose in a sample as recited in claim 1, wherein:

the predetermined narrow wavelength band ranges from about 330 nanometers to about 360 nanometers.

3. Apparatus for determining the concentration of glucose in a sample as recited in claim 1, wherein the sensor generates a plurality of electrical signals that indicate the intensity of return light substantially continuously across an extended wavelength spectrum associated with the emission light.

4. Apparatus for determining the concentration of glucose in a sample as recited in claim 1, further including one or more waveguides for transmitting the excitation light from the light source to the sample and for transmitting the return light from the sample to the sensor.

5. Apparatus for determining the concentration of glucose in a sample as recited in claim 1, wherein the sensor includes:

a first detector adapted to detect the return light within a first wavelength band and generate a first electrical signal;

a second detector adapted to detect the return light within a second wavelength band and generate a second electrical signal; and

a third detector adapted to detect the return light within a third wavelength band and generate a third electrical signal.

6. Apparatus for determining the concentration of glucose in a sample as recited in claim 3, wherein the predictive model is defined by six latent variables.

7. Apparatus for determining the concentration of glucose in a sample as recited in claim 1, wherein the predictive model is defined by prediction coefficients that are associated with the glucose concentration distinguishing characteristics.

8. Apparatus for determining the concentration of glucose in a sample as defined in claim 1, wherein:

the energy of the excitation light is varied over a plurality of predetermined energy levels; and

the sensor generates, at each energy level, a first electrical signal based on the intensity of return light within a wavelength of the emission light associated with raman scattering, and a second electrical signal based on the intensity of return light within a wavelength band of the emission light associated with a peak of a broad glucose emission band.

9. An apparatus for determining the concentration of glucose in a sample that includes water, comprising:

a light source that emits ultraviolet excitation light that is varied over a plurality of predetermined energy levels and directed at a sample to produce return light from the sample, such that the return light includes induced emissions of light produced as a result of interactions between the excitation light and any glucose with water present in the sample;

a sensor that monitors the return light and generates, at each energy level of the excitation light, an electrical signal indicative of a first intensity of return light within a wavelength of the return light associated with raman scattering, and an electrical signal indicative of a second intensity of return light within a wavelength of the return light associated with glucose emission; and

a processor that processes the electrical signals, using a predictive model, to determine the concentration of glucose in the sample.

10. A method for determining the concentration of glucose in a sample including water, comprising:

exciting the sample with excitation light at a plurality of energy levels;

measuring, at each energy level, a first intensity of return light within a wavelength of the return light associated with raman scattering;

measuring, at each energy level, a second intensity of return light within a wavelength of the return light associated with glucose emission;

determining the concentration of glucose using a predictive model incorporating the first intensity measurements and the second intensity measurements.

11. Apparatus for determining the concentration of glucose in a sample that includes water, comprising:

a light source that emits ultraviolet excitation light of at least one predetermined energy level, that is directed at a sample to produce return light from the sample, such return light including induced emissions of light produced as a result of interactions between the excitation light and any glucose with water present in the sample;

a sensor that monitors the return light within eight different wavelength bands and generates eight electrical signals indicative of the intensity of return light within respective wavelength bands, and which are associated with glucose concentration distinguishing characteristics of the emission light; and

a processor that processes the electrical signals, using a predictive model, to determine the concentration of glucose in the sample.

12. Apparatus for determining the concentration of glucose in a sample as recited in claim 11, wherein:

the wavelength of the excitation light is about 308 nanometers;

the first wavelength band is a narrow wavelength band centered at about 342 nanometers;

the second wavelength band is a narrow wavelength band centered at about 344 nanometers;

the third wavelength band is a narrow wavelength band centered at about 347 nanometers;

the fourth wavelength band is a narrow wavelength band centered at about 352 nanometers;

the fifth wavelength band is a narrow wavelength band centered at about 360 nanometers;

the sixth wavelength band is a narrow wavelength band centered at about 370 nanometers;

the seventh wavelength band is a narrow wavelength band centered at about 385 nanometers; and

the eighth wavelength band is a narrow wavelength band centered at about 400 nanometers.

13. A method of determining the concentration of glucose in a sample with water, comprising:

providing a regression model that accounts for a nonlinear relationship between the concentration of glucose in a sample and an electrical signal based on certain glucose concentration distinguishing characteristics of a light emission spectrum that includes emission light produced by glucose related interactions with the excitation light;

causing a sample to produce a light emission spectrum that includes ultraviolet emission light produced by glucose related interaction and generating a plurality of electrical signals that represent the glucose concentration distinguishing characteristics, at least two of the plurality of electrical signals indicative of the intensity of return light at a respective number of wavelengths within a predetermined, narrow, wavelength band corresponding to at least one characteristic narrow spectral peak, and at least a third of the plurality of electrical signals indicative of the intensity of return light within a predetermined, narrow wavelength band outside of the narrow spectral peak; and

processing, using the regression model, the plurality of electrical signals to determine the glucose concentration and generating an electrical signal based on the glucose concentration determined using the regression model.