Method and device for analyte measurement

Abstract

A device for non-invasively measuring concentration of one or more analytes in a living subject or a biological sample, wherein the device includes several light sources, a system for controlling the timing and intensity of the light source outputs, a system for passing the light through the subject or sample, a system for measuring the amount of light transmitted, and a system for relating the measurement to the concentration of the analyte in question. The light sources are narrow band sources at different wavelengths, and are capable of being rapidly switched between two levels of intensity. The actual number of light sources required and the wavelengths of the sources are dependent upon the specific analyte being measured.

Claimed is: 
     
         1 . An apparatus for measuring a concentration of a target analyte in a sample containing at least one alternate analyte, the apparatus comprising:
 a plurality of light sources for generating a plurality of light wavelength bands, each band of a narrow wavelength;   a temperature monitoring module consisting of at least one of (1) a thermocouple; (2) a thermistor; and (3) a voltage drop measurement apparatus adapted to measure voltage drop across a semiconductor junction of at least one of the plurality of light sources;   the plurality of light sources being operatively connected to the temperature monitoring module to control effects of internal temperature on light output of the at least one light source, according to a calibration model.   
     
     
         2 . The apparatus of  claim 1 , further comprising:
 a light combination module adapted to combine the plurality of light bands into a narrow beam;   a focusing module adapted to direct the narrow beam onto the sample;   a light detection module adapted to detect light from the apparatus having passed through or reflected from the sample;   a measurement module adapted to measure the intensity of the light which has passed through or reflected from the sample; and   a determination module adapted to determine the concentration of the target analyte based on the intensity of the light which has passed through or reflected from the sample.   
     
     
         3 . The apparatus of  claim 2 , wherein the apparatus further includes a temperature control module adapted to control the internal temperatures of at least one of the plurality of light sources using either a single heat reservoir thermal model or a multiple heat reservoir thermal model. 
     
     
         4 . The apparatus of  claim 2 , wherein the apparatus adjusts input levels to each of the plurality of light sources in order to compensate for known changes in light output resulting from changes in temperature of the light sources. 
     
     
         5 . The apparatus of  claim 3 , wherein the temperature control module is further adapted to at least one of (1) infer past internal temperatures over time of and (2) predict future temperatures of at least one of the plurality of light sources. 
     
     
         6 . The apparatus of  claim 5 , wherein the temperature control module is further adapted to estimate the parameters of the thermal models using observations of the heating and cooling rates of the light sources as the internal temperatures are experimentally manipulated. 
     
     
         7 . The apparatus of  claim 5 , wherein the temperature control module is further adapted to turn on the plurality of light sources in a manner so that each of the plurality of light sources reaches a target temperature simultaneously. 
     
     
         8 . The apparatus of  claim 7 , further comprising a light stabilization module adapted to:
 divert a portion of the narrow beam before it passes through or is reflected from the sample;   measure the strength of the diverted portion of the narrow beam; and   use the narrow beam strength measurement to stabilize light output of each of the plurality of light sources.   
     
     
         9 . The apparatus of  claim 8 , wherein the light stabilization module is further adapted to stabilize the light output of each of the plurality of light sources using a thermoelectric cooler. 
     
     
         10 . The apparatus of  claim 8 , wherein the light stabilization module is further adapted to stabilize the light output of each of the plurality of light sources by turning the plurality of light sources on and off for controlled periods wherein the controlled periods are calculated using a heating model of the plurality of light sources. 
     
     
         11 . A method of measuring a concentration of a target analyte in a sample containing at least one a plurality of alternate analyte, the method comprising:
 predetermining a generated set of non-monochromatic wavelength intensity distributions to control a measured difference between the sums of at least two wavelength intensity distributions within a measured set of wavelength intensity distributions;   generating a plurality of light wavelength bands, together comprising at least one of said predetermined non-monochromatic wavelength intensity distributions;   combining said generated plurality of light wavelength bands into a single narrow beam so that the combined light bands comprise at least one of said predetermined wavelength intensity distributions;   projecting each of said set of predetermined generated wavelength intensity distributions alternately within the single narrow beam;   directing the narrow beam onto the sample;   measuring an intensity of the narrow beam which has passed through or reflected from the sample; and   determining the concentration of the target analyte based on said differences between the sums of the measured wavelength intensity distributions within the narrow beam which has passed through or reflected from the sample.   
     
     
         12 . The method of  claim 11 , wherein generating a plurality of light wavelength bands further comprises generating at least three distinct light wavelength bands using a plurality of light sources, each generating one or more of the plurality of light bands. 
     
     
         13 . The method of  claim 12 , further comprising controlling an average or instantaneous intensity of each of the plurality of light bands. 
     
     
         14 . The method of  claim 12 , wherein the wavelength intensity distributions are predetermined by a calculation which uses orthogonal vectors. 
     
     
         15 . The method of  claim 14 , wherein the narrow beam of projected generated light wavelength intensity distributions alternately comprises a first set of light wavelength bands with positive intensities in the predetermination calculation and a second set of light wavelength bands with negative intensities in the predetermination calculation. 
     
     
         16 . The method of  claim 12 , wherein generating the plurality of light bands further comprises generating at least two sets of light bands such that when the narrow beam passes through or is reflected from the sample, a difference between the average measured intensities of the combined light bands within one said set and the combined light bands within at least one other said set of light bands in the narrow beam having passed through or reflected from the sample is a function of the concentration of the target analyte in the sample and is independent of the concentrations of the alternate analytes in the sample. 
     
     
         17 . The method of  claim 12 , wherein alternately projecting the plurality of light bands further comprises switching each of the plurality of light sources between two or more predetermined intensity levels in a synchronous manner such that at any given time the combined plurality of light bands in the narrow beam comprises one of the predetermined wavelength intensity distributions. 
     
     
         18 . The method of  claim 17 , wherein determining the concentration of the target analyte further comprises determining the concentration of the target analyte in a composition of analytes wherein for each said at least one alternate analyte which varies in concentration, the target analyte absorbs in a manner different than said at least one alternate analyte for at least one of the plurality of light bands. 
     
     
         19 . The method of  claim 12 , wherein combining the plurality of light bands further comprises combining the plurality of light bands using a fiber optic assembly. 
     
     
         20 . The method of  claim 12 , wherein detecting the narrow light beam further comprises generating an electrical signal proportional to the light passing through or reflected from the sample. 
     
     
         21 . The method of  claim 17 , wherein measuring the intensity of the narrow beam further comprises integrating the electrical signal using a switching pattern used to switch each of the plurality of light sources between the two or more predetermined intensity levels. 
     
     
         22 . The method of  claim 12 , further comprising monitoring internal temperature of at least one of the plurality of light sources and calibrating output of the plurality of light sources according to their internal temperatures. 
     
     
         23 . A method of measuring a concentration of a target analyte in a sample containing at least one alternate analyte, the method comprising:
 generating a plurality of light wavelength bands each band of a narrow wavelength;   switching each of the plurality of light wavelength bands between two or more predetermined wavelength intensity distributions;   wherein generating a plurality of light wavelength bands further comprises generating a plurality of light bands using a plurality of light sources; and   further comprising monitoring the internal temperature of at least one of the plurality of light sources using at least one of: (1) a thermocouple; (2) a thermistor; and (3) a voltage drop measurement apparatus adapted to measure voltage drop across a semiconductor junction of the at least one of the plurality of light sources; and calibrating output of the plurality of light sources according to their internal temperatures.   
     
     
         24 . The method of  claim 23 , further comprising:
 combining the plurality of light bands into a narrow beam;   directing the narrow beam onto the sample;   measuring the intensity of the narrow beam which has passed through or reflected from the sample; and   determining the concentration of the target analyte based on the intensity of the narrow beam which has passed through or reflected from the sample.   
     
     
         25 . The method of  claim 24 , wherein generating the plurality of bands further comprises controlling the internal temperature of at least one of the plurality of light sources using either a single heat reservoir-thermal model or a multiple hear reservoir thermal model. 
     
     
         26 . The method of  claim 24 , wherein generating the plurality of bands further comprises adjusting an input level to each of the plurality of light sources in order to compensate for known changes in light output resulting from changes in internal temperature of the light sources. 
     
     
         27 . The method of  claim 25 , wherein controlling the internal temperature of at least one of the plurality of light sources further comprises estimating the parameters of the thermal models using observations of the heating and cooling rates of the light sources as the internal temperatures are experimentally manipulated. 
     
     
         28 . The method of  claim 25 , wherein controlling the internal temperature of at least one of the plurality of light sources further comprises turning on the plurality of light sources in a manner so that each of the plurality of light sources reaches a target temperature simultaneously. 
     
     
         29 . The method of  claim 25 , further comprising:
 diverting a portion of the narrow beam before it passes through or is reflected from the sample;   measuring the strength of the diverted portion of the narrow beam; and   using the narrow beam strength measurement to stabilize light output of each of the plurality of light sources.   
     
     
         30 . An apparatus for measuring a concentration of a target analyte in a sample containing at least one alternate analyte, the apparatus comprising:
 a light generation module adapted to generate a plurality of light wavelength bands each band of a narrow wavelength;   wherein the light generation module further comprises a plurality of light sources, each of the plurality of light sources adapted to generate one or more of the plurality of light bands;   wherein the light generation module is further adapted to monitor the internal temperature of at least one of the plurality of light sources using at least one of: (1) a thermocouple; (2) a thermistor; and (3) a voltage drop measurement apparatus adapted to measure voltage drop across a semiconductor junction of the at least one of the plurality of light sources; and   wherein the light generation module is further adapted to calibrate output of the plurality of light sources according to their internal temperatures.