Biomarker normalization

Abstract

A fluid sample is measured with a tear film measuring system that includes a processing device that receives a sample chip comprising a sample region configured to contain an aliquot volume of sample fluid, the processing device configured to perform analyses of osmolarity and of one or more biomarkers within the sample fluid, wherein the analysis of biomarkers includes normalization of biomarker concentration values.

1 .- 37 . (canceled) 
     
     
         38 . A tear fluid measuring system, comprising:
 (a) a processing device, and   (b) a sample region configured to contain an aliquot volume of tear fluid,   wherein the processing device analyzes concentration of a biomarker within the aliquot volume of the tear fluid, and normalizes the concentration of the biomarker to produce an adjusted biomarker concentration.   
     
     
         39 . The fluid measuring system of  claim 38 , further comprising at least one electrode with which the concentration of the biomarker is normalized. 
     
     
         40 . The fluid measuring system of  claim 38 , wherein the processing device normalizes the concentration of the biomarker against osmolarity of the tear fluid. 
     
     
         41 . The fluid measuring system of  claim 38 , wherein the adjusted biomarker concentration corrects for patient-specific tear homeostasis. 
     
     
         42 . The fluid measuring system of  claim 38 , wherein the sample region comprises a plurality of electrodes. 
     
     
         43 . The fluid measuring system of  claim 42 , wherein the plurality of electrodes are coupled to a conductive polymer. 
     
     
         44 . The fluid measuring system of  claim 42 , wherein the plurality of electrodes are coupled to an electrochemical transducer for the biomarker. 
     
     
         45 . The fluid measuring system of  claim 38 , wherein the biomarker is selected from: an immunoglobulins, glucose, insulin, lactoferrin, tear lysozyme, a cytokine, a hormone, a hormone metabolite, an infectious disease phenotype, a nucleic acid, a protein, and lipid fraction. 
     
     
         46 . The fluid measuring system of  claim 45 , wherein the biomarker is glucose. 
     
     
         47 . The fluid measuring system of  claim 38 , wherein the normalization of biomarker concentration values is linear. 
     
     
         48 . The fluid measuring system of  claim 38 , wherein the normalization of biomarker concentration values is ratiometric. 
     
     
         49 . The fluid measuring system of  claim 38 , wherein the normalization of biomarker concentration values is based on a calibration curve. 
     
     
         50 . A method of measuring the concentration of a biomarker in tear fluid, comprising:
 (a) receiving a biomarker output signal from a sample region of a sample chip, wherein the biomarker output signal correlates with the concentration of the biomarker in the tear fluid;   (b) processing the biomarker output signal to produce a biomarker concentration value for the tear fluid; and   (c) normalizing the biomarker concentration value to produce an adjusted biomarker concentration.   
     
     
         51 . The method of  claim 50 , wherein normalizing the biomarker concentration value utilizes an electrode. 
     
     
         52 . The method of  claim 50 , wherein the sample region of the sample chip comprise a plurality of electrodes configured as an electrochemical transducer for the biomarker. 
     
     
         53 . The method of  claim 52 , further comprising imparting energy into the tear fluid and producing the biomarker output signal by transducing the energy with the plurality of electrodes configured as an electrochemical transducer. 
     
     
         54 . The method of  claim 49 , wherein the biomarker is: an immunoglobulin, glucose, insulin, lactoferrin, tear lysozyme, a cytokine, a hormone, a hormone metabolite, an infectious disease phenotype, a nucleic acid, a protein, or lipid fraction. 
     
     
         55 . The method of  claim 50 , wherein the biomarker is glucose. 
     
     
         56 . The method of  claim 50 , wherein the biomarker is IgE, IgA, IgG, or IgM. 
     
     
         57 . The method of  claim 50 , further comprising receiving an osmolarity output signal from the sample region of the sample chip, wherein the osmolarity output signal correlates with the osmolarity of the tear fluid. 
     
     
         58 . The method of  claim 57 , wherein the sample region of the sample chip further comprises a plurality of electrodes configured as an osmolarity transducer. 
     
     
         59 . The method of  claim 58 , further comprising (a) imparting energy into the tear fluid, and (b) producing an osmolarity output signal by transducing the energy with the plurality of electrodes configured as an osmolarity transducer. 
     
     
         60 . The method of  claim 57 , wherein the osmolarity output signal and the biomarker output signal are generated simultaneously or in parallel operations. 
     
     
         61 . The method of  claim 57 , wherein the processing device normalizes the concentration of the biomarker against osmolarity of the tear fluid. 
     
     
         62 . The method of  claim 50 , wherein the adjusted biomarker concentration corrects for patient-specific tear homeostasis. 
     
     
         63 . The method of  claim 50 , wherein normalization of biomarker concentration values is linear. 
     
     
         64 . The method of  claim 50 , wherein normalization of biomarker concentration values is ratiometric. 
     
     
         65 . The method of  claim 50 , wherein normalization of biomarker concentration values is based on a calibration curve. 
     
     
         66 . The method of  claim 50 , further comprising depositing an aliquot volume of the tear fluid on the sample region of the sample chip.