Methods and devices for correlating a biomarker in a non-blood bodily fluid with the biomarker in blood

Abstract

Disclosed is a method for correlating a biomarker in a non-blood bodily fluid with the same biomarker in the blood of an individual, including: measuring, in a first period in time, the biomarker in non-blood bodily fluid and measuring the same biomarker in the blood of the same individual to establish an R ratio of [NBBF1]/[BB1], where [NBBF1] is the biomarker concentration in non-blood bodily fluid in the first period in time, and [BB1] is the biomarker concentration in the blood in the first period in time; storing the ratio in a memory; measuring, in a second period in time, the biomarker in non-blood bodily fluid to determine [NBBF2], where [NBBF2] is the biomarker concentration in the non-blood bodily fluid in the second period in time; and correlating the measured [NBBF2] with the R ratio to generate a correlated [BB2] biomarker concentration in the blood of the individual in the second period in time. Also disclosed is a device, apparatus, and method for correlating the glucose concentration in a non-blood bodily fluid such as saliva with the glucose in the blood of an individual.

What is claimed is: 
     
         1 . An instrument for correlating a biomarker in a non-blood bodily fluid with the same biomarker in the blood of an individual, comprising a device, wherein the device that:
 (f) measures, in a first period in time, the biomarker in non-blood bodily fluid and measuring the same biomarker in the blood of the same individual,   (g) establishes an R ratio equal to [NBBF1] divided by [BB1], wherein [NBBF1] is the biomarker concentration in the non-blood bodily fluid in the first period in time, and [BB1] is the biomarker concentration in the blood in the first period in time;   (h) stories the R ratio in a non-transitory storage medium;   (i) measures, in a second period in time, the biomarker in non-blood bodily fluid to determine [NBBF2], where [NBBF2] is the biomarker concentration in the non-blood bodily fluid in the second period in time; and   (j) correlates the measured [NBBF2] with the R ratio to generate a correlated [BB2] biomarker concentration in blood of the individual in the second period in time.   
     
     
         2 . The instrument of  claim 1 , wherein the device comprises a sample holder that is a Q-Card. 
     
     
         3 . The instrument of  claim 1 , wherein the device comprises an imager that images the sample in measuring the biomarkers. 
     
     
         4 . A method for correlating a biomarker in a non-blood bodily fluid with the same biomarker in the blood of an individual, comprising:
 obtaining the device of  claim 1 ,   using the device to:   (d) measuring, in a first period in time, the biomarker in non-blood bodily fluid and measuring the same biomarker in the blood of the same individual to establish an R ratio equal to [NBBF1]/[BB1], where [NBBF1] is the biomarker concentration in the non-blood bodily fluid in the first period in time, and [BB1] is the biomarker concentration in the blood in the first period in time;   (e) storing the R ratio in a memory;   (f) measuring, in a second period in time, the biomarker in non-blood bodily fluid to determine [NBBF2], where [NBBF2] is the biomarker concentration in the non-blood bodily fluid in the second period in time; and   d) correlating the measured [NBBF2] with the R ratio to generate a correlated [BB2] biomarker concentration in blood of the individual in the second period in time.   
     
     
         5 . The method of  claim 4 , further comprising periodically calibrating the ratio R to establish a recalibrated [NBBFX]/[BBX] ratio, where X is the n th  period of time where n is for 3 to 100. 
     
     
         6 . The method of  claim 5 , wherein calibrating is selected from: one pair of calibration tests; or several pairs of calibration tests, and the calibration tests are over a period of time to establish an [NBBFA]/[BBA] average ratio, where [NBBFA] is the average biomarker concentration in non-blood bodily fluid and [BBA] is the average biomarker concentration in the blood of the individual over the period of time. 
     
     
         7 . The method of  claim 5 , wherein periodically calibrating is accomplished in a period selected from hourly, daily, weekly, monthly, semi-annually, annually, or a combination thereof, including intermediate values and ranges. 
     
     
         8 . The method of  claim 5 , wherein establishing a recalibrated [NBBFX]/[BBX] ratio is accomplished in at least one period of time selected from: each minute, each hour, each morning, each noon day, each night, each midnight, each day, each week, each month, each semi-annual, each annual, each bi-annual, including intermediate periods-in-time and ranges. 
     
     
         9 . The method of  claim 4 , wherein correlating is accomplished by solving for [BB2] in the formula:
   [NBBF2]/[BB2]=R,   or rearranged and substituting for R:
   [BB2]=[BB1]/[NBBF1] [NBBF2]. 
   
     
     
         10 . The method of  claim 5 , wherein the difference between the first time period and the second time period is at least one of: from 5 to 10 minutes, from 20 to 30 minutes, from 30 to 40 minutes, from 40 to 50 minutes, from 50 to 60 minutes, hourly, daily, weekly, monthly, semi-annually, annually, or bi-annually, including intermediate values and ranges. 
     
     
         11 . The method of  claim 4 , wherein storing the R ratio in a memory is accomplished with a mobile communication device. 
     
     
         12 . The method of  claim 4 , wherein the non-blood bodily fluid is saliva, and the periodically calibrating is accomplished in a period selected from at least one interval of hourly, daily, weekly, monthly, semi-annually, annually, or a combination thereof, including intermediate values and ranges. 
     
     
         13 . The method of  claim 4 , further comprising applying machine learning (ML) to improve the accuracy of the method by human comparison of at least one of: preliminary results; secondary results; or tertiary results, generated by a device having segregated sample deposition regions and an associated imaging apparatus or an analyte concentration measuring apparatus. 
     
     
         14 . The method of  claim 4 , wherein the biomarker is glucose, and wherein the R is a ratio of the glucose in non-blood bodily fluid measured in the first period in time and the glucose the blood of the same individual measured in the first period in time [GNBF1]/[GB1]. 
     
     
         15 . The method of  claim 14 , wherein the non-blood bodily fluid is saliva. 
     
     
         16 . The method of  claim 14 , further comprising periodically calibrating the [GNBF1]/[GB1] ratio to establish a recalibrated [GNBFX]/[GBX] ratio, where X is the n th  period of time where n is for 3 to 100. 
     
     
         17 . The method of  claim 16 , wherein establishing a recalibrated [GNBFX]/[GBX] ratio is accomplished in at least one period-of-time interval selected from: each minute, each hour, each morning, each noon day, each night, each midnight, each day, each week, each month, each semi-annual, each annual, each bi-annual, including intermediate periods-in-time and ranges. 
     
     
         18 . The method of  claim 14 , wherein storing the [GNBF1]/[GB1] ratio in a memory is accomplished in a mobile communication device and analyzed by software in the mobile communication device. 
     
     
         19 . The instrument of  claim 1 , further comprising a non-transitory storage medium that stores machine learning (ML) model that improves the accuracy of the method by human comparison of at least one of: preliminary results; secondary results; or tertiary results, generated by a device having segregated sample deposition regions and an associated imaging apparatus or an analyte concentration measuring apparatus. 
     
     
         20 . The instrument of  claim 1 , the device further periodically calibrates the ratio R to establish a recalibrated [NBBFX]/[BBX] ratio, where X is the n th  period of time where n is for 3 to 100. 
     
     
         21 . The instrument of  claim 20 , wherein calibrating is selected from: one pair of calibration tests; or several pairs of calibration tests, and the calibration tests are over a period of time to establish an [NBBFA]/[BBA] average ratio, where [NBBFA] is the average biomarker concentration in non-blood bodily fluid and [BBA] is the average biomarker concentration in the blood of the individual over the period of time. 
     
     
         22 . The instrument of  claim 20 , wherein periodically calibrating is accomplished in a period selected from hourly, daily, weekly, monthly, semi-annually, annually, or a combination thereof, including intermediate values and ranges. 
     
     
         23 . The instrument of  claim 20 , wherein establishing a recalibrated [NBBFX]/[BBX] ratio is accomplished in at least one period of time selected from: each minute, each hour, each morning, each noon day, each night, each midnight, each day, each week, each month, each semi-annual, each annual, each bi-annual, including intermediate periods-in-time and ranges. 
     
     
         24 . The instrument of  claim 1 , wherein correlating is accomplished by solving for [BB2] in the formula:
   [NBBF2]/[BB2]=R,   or rearranged and substituting for R:
   [BB2]=[BB1]/[NBBF1] [NBBF2]. 
   
     
     
         25 . The instrument of  claim 1 , wherein the difference between the first time period and the second time period is at least one of: from 5 to 10 minutes, from 20 to 30 minutes, from 30 to 40 minutes, from 40 to 50 minutes, from 50 to 60 minutes, hourly, daily, weekly, monthly, semi-annually, annually, or bi-annually, including intermediate values and ranges. 
     
     
         26 . The instrument of  claim 1 , wherein the non-blood bodily fluid is saliva, and the periodically calibrating is accomplished in a period selected from at least one interval of hourly, daily, weekly, monthly, semi-annually, annually, or a combination thereof, including intermediate values and ranges. 
     
     
         27 . The instrument of  claim 1 , wherein the biomarker is glucose. 
     
     
         28 . The instrument of  claim 1 , wherein the non-blood bodily fluid is saliva. 
     
     
         29 . The instrument of  claim 1 , further the device further periodically calibrates the [GNBF1]/[GB1] ratio to establish a recalibrated [GNBFX]/[GBX] ratio, where X is the n th  period of time where n is for 3 to 100. 
     
     
         30 . The instrument of  claim 30 , wherein establishing a recalibrated [GNBFX]/[GBX] ratio is accomplished in at least one period-of-time interval selected from: each minute, each hour, each morning, each noon day, each night, each midnight, each day, each week, each month, each semi-annual, each annual, each bi-annual, including intermediate periods-in-time and ranges. 
     
     
         31 . The instrument of  claim 30 , wherein storing the [GNBF1]/[GB1] ratio in a memory is accomplished in a mobile communication device and analyzed by software in the mobile communication device.