Measurement devices and methods for measuring analyte concentration incorporating temperature and ph correction

Abstract

Disclosed herein are methods of estimating an analyte concentration which include generating a signal indicative of the analyte concentration, generating a signal indicative of a temperature, generating a signal indicative of a pH, and transforming the signal indicative of the analyte concentration utilizing an equation of the form of a modified Michaelis-Menten equation depending on Michaelis-Menten parameters, wherein values of the Michaelis-Menten parameters are set based upon data which includes temperature and pH calibration parameters, the signal indicative of a temperature, and the signal indicative of a pH. Also disclosed herein are measurement devices which employ the aforementioned methods.

1 - 27 . (canceled) 
     
     
         28 . A measurement device for estimating glucose concentration comprising:
 an optical sensor comprising a non-enzymatic, equilibrium fluorescence chemical indicator system disposed along a distal region of an optical fiber, the chemical indicator system comprising a fluorophore operably coupled to a glucose binding moiety, wherein the fluorophore is configured to generate a fluorescent emission signal upon excitation with light, and wherein glucose binding to the glucose binding moiety causes a change in an intensity of the fluorescent emission signal related to the glucose concentration;   a pH sensor configured to generate a signal indicative of a pH; and   a receiving and processing unit configured to transform the fluorescent emission signal intensity utilizing a first equation for correcting the glucose concentration for changes in pH, wherein the first equation is:   
       
         
           
             
               
                 
                   [ 
                   Glu 
                   ] 
                 
                 = 
                 
                   
                     
                       c 
                       pH 
                     
                     * 
                     
                       ⌊ 
                       
                         
                           G 
                           i 
                         
                         - 
                         
                           a 
                           pH 
                         
                       
                       ⌋ 
                     
                   
                   
                     
                       a 
                       pH 
                     
                     + 
                     
                       b 
                       pH 
                     
                     - 
                     
                       G 
                       i 
                     
                   
                 
               
               , 
             
           
         
       
       wherein
 [Glu] is the estimated glucose concentration. 
 G i  is the fluorescent emission signal intensity; 
 a pH  is the fluorescent emission signal intensity in the absence of glucose at a particular pH, 
 b pH  is the asymptotic signal intensity at infinite glucose concentration, minus the fluorescent signal intensity in the absence of glucose (a pH ) at the same particular pH, and 
 c pH  is the glucose concentration at which the fluorescent signal intensity is one-half of the difference between the asymptotic (b pH ) and the background (a pH ) at the same particular pH; 
 wherein a pH , b pH , and c pH  are set based on data comprising:
 pH calibration data; and 
 the signal indicative of pH. 
 
 
     
     
         29 . The measurement device of  claim 28 , further comprising:
 a temperature sensor configured to generate a signal indicative of a temperature;   wherein the receiving and processing unit is further configured to transform the fluorescent emission signal intensity utilizing a second equation for correcting the glucose concentration for changes in pH and temperature, wherein the second equation is:   
       
         
           
             
               
                 
                   [ 
                   Glu 
                   ] 
                 
                 = 
                 
                   
                     
                       c 
                       
                         T 
                         , 
                         pH 
                       
                     
                     * 
                     
                       ⌊ 
                       
                         
                           G 
                           i 
                         
                         - 
                         
                           a 
                           
                             T 
                             , 
                             pH 
                           
                         
                       
                       ⌋ 
                     
                   
                   
                     
                       a 
                       
                         T 
                         , 
                         pH 
                       
                     
                     + 
                     
                       b 
                       
                         T 
                         , 
                         pH 
                       
                     
                     - 
                     
                       G 
                       i 
                     
                   
                 
               
               , 
             
           
         
         wherein
 a T,pH  is the fluorescent emission signal intensity in the absence of glucose at a particular pH and temperature, 
 b T,pH  is the asymptotic signal intensity at infinite glucose concentration, minus the fluorescent signal intensity in the absence of glucose (a T,pH ) at the same particular pH and temperature, and 
 c T,pH  is the glucose concentration at which the fluorescent signal intensity is one-half of the difference between the asymptotic (b T,pH ) and the background (a T,pH ) at the same particular pH and temperature; 
 wherein a T,pH , b T,pH , and b T,pH  are set based on data comprising:
 temperature data; and 
 the signal indicative of temperature. 
 
 
       
     
     
         30 . The measurement device of  claim 28 , wherein the optical sensor further comprises:
 at least one light source configured to generate light; and   at least one detector configured to detect the fluorescent emission signal intensity and generate a signal indicative of the glucose concentration.   
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The measurement device of  claim 28 , wherein the indicator system further comprises an immobilizing medium configured to prevent the fluorophore and/or the binding moiety from diffusing out of the sensor. 
     
     
         35 . The measurement device of  claim 29 , wherein the temperature sensor and the optical sensor are co-located along the distal region of the optical fiber. 
     
     
         36 . The measurement device of  claim 29 , wherein the optical sensor further comprises:
 at least one light source configured to generate light; and   at least one detector configured to detect the fluorescent emission signal intensity and generate a signal indicative of the glucose concentration.   
     
     
         37 . The measurement device of  claim 29 , wherein the indicator system further comprises an immobilizing medium configured to prevent the fluorophore and/or the binding moiety from diffusing out of the sensor. 
     
     
         38 . The measurement device  claim 28 , wherein the fluorophore is HPTS-triCys-MA. 
     
     
         39 . The measurement device  claim 28 , wherein the glucose binding moiety comprises boronic acid. 
     
     
         40 . The measurement device of  claim 28 , wherein a pH , is defined by the equation a pH =a 7.4 *ρ a     pH   (pH), wherein b pH  is defined by the equation b pH =b 7.4 *ρ b     pH   (pH), and wherein c pH  is defined by the equation c pH =c 7.4 *ρ c     pH   (pH). 
     
     
         41 . The measurement device of  claim 29 , wherein a T,pH  is defined by the equation a T,pH =a 0 *τ a     T   (T)*ρ a     pH   (pH), wherein b T,pH  is defined by the equation b T,pH =b 0 *τ b     T   (T)*ρ b     pH   (pH), and wherein c T,pH  is defined by the equation c T,pH =b 0 *τ c     T   (T)*ρ c     pH   (pH).