Normalizing the response of a fluorescence instrument using spectral response

Abstract

A method to normalize at least one of a population of subordinate clinical diagnostic analyzer to a master clinical diagnostic analyzer such that an assay result from a subordinate clinical diagnostic analyzer can be converted to the equivalent result of the master clinical diagnostic analyzer by using a simple multiplicative factor when the assay executed on each analyzer uses a common fluorescently labeled dye. Also a method to re-normalize a subordinate clinical diagnostic analyzer assay result to a master clinical diagnostic analyzer assay result by using a simple multiplicative factor when the assay executed on the subordinate clinical diagnostic analyzer uses a different fluorescently labeled dye than the assay executed on the master clinical diagnostic analyzer.

We claim: 
     
         1 . A method of normalizing a first diagnostic result of a subordinate clinical diagnostic analyzer to a second diagnostic result of a master clinical diagnostic analyzer comprising the steps of
 obtaining a normalized excitation intensity spectrum of the master clinical diagnostic analyzer,   obtaining a normalized excitation intensity spectrum of the subordinate clinical diagnostic analyzer,   obtaining a normalized responsivity intensity spectrum of the master clinical diagnostic analyzer,   obtaining a normalized responsivity intensity spectrum of the subordinate clinical diagnostic analyzer,   obtaining a normalized excitation/emission spectrum of a solid inorganic photostable fluorophore calibration target,   reading the solid inorganic photostable fluorophore calibration target in the master clinical diagnostic analyzer thereby obtaining a first response value,   reading the solid inorganic photostable fluorophore calibration target in the subordinate clinical diagnostic analyzer thereby obtaining a second response value,   determining the gain ratio of the master clinical diagnostic analyzer to the subordinate clinical diagnostic analyzer based upon the two above obtained response values,   determining a multiplicative normalization factor between a normalized subordinate clinical diagnostic analyzer and the master clinical diagnostic analyzer,   determining the relative adsorption/emission spectrum of a first fluorescently labeled dye whereas the first fluorescently labeled dye is a diagnostic assay component,   obtaining a first diagnostic result from a specific patient specimen or sample incorporating the first fluorescently labeled dye using the normalized subordinate clinical diagnostic analyzer, and   modifying the first diagnostic result by the multiplicative normalization factor to obtain a second diagnostic result wherein the second diagnostic result is a normalized approximation to a diagnostic result which would be obtained by analyzing the specific patient specimen or sample on the master clinical diagnostic analyzer.   
     
     
         2 . A method to re-normalize a subordinate clinical diagnostic analyzer assay result as compared to a master clinical diagnostic analyzer assay result comprising the steps of
 normalizing the subordinate clinical diagnostic analyzer as claimed in  claim 1 ,   determining a relative adsorption/intensity spectrum of a second fluorescently labeled dye whereas the second fluorescently labeled dye is a diagnostic assay component,   determining a re-normalization multiplicative factor between a subordinate clinical diagnostic analyzer and a master clinical diagnostic analyzer,   obtaining a first diagnostic result from a specific patient specimen or sample incorporating the second fluorescently labeled dye using the normalized subordinate clinical diagnostic analyzer, and   modifying the first diagnostic result by the re-normalization factor to obtain a second diagnostic result wherein the second diagnostic result is a normalized approximation to a diagnostic result which would be obtained by analyzing the specific patient specimen or sample on the master clinical diagnostic analyzer.   
     
     
         3 . A method as claimed in  claim 1 , wherein the solid inorganic photostable fluorophore is a phosphate matrix glass. 
     
     
         4 . A method as claimed in  claim 2 , wherein the phosphate matrix glass is a bismuth-doped phosphate glass. 
     
     
         5 . A method as claimed in  claim 2 , wherein the phosphate matrix glass is a copper-doped phosphate glass. 
     
     
         6 . A method as claimed in  claim 1 , wherein the modification of the first diagnostic result by the multiplicative normalization factor to obtain the second diagnostic result is accomplished by numerical multiplication. 
     
     
         7 . A method as claimed in  claim 1 , wherein the modification of the first diagnostic result by the multiplicative normalization factor to obtain the second diagnostic result is accomplished by using a linear calibration curve having a differing slope. 
     
     
         8 . A method as claimed in  claim 2 , wherein the modification of the first diagnostic result by the multiplicative re-normalization factor to obtain the second diagnostic result is accomplished by numerical multiplication. 
     
     
         9 . A method as claimed in  claim 2 , wherein the modification of the first diagnostic result by the multiplicative re-normalization factor to obtain the second diagnostic result is accomplished by using a linear calibration curve having a differing slope. 
     
     
         10 . A method as claimed in  claim 1 , wherein the modification of the first diagnostic result by the multiplicative normalization factor to obtain the second diagnostic result in the case of a non-linear calibration curve is accomplished by numerical multiplication.