Monitoring one or more solutes in a biological system using optical techniques

Abstract

This invention is a scheme for monitoring a solute in a biological system comprising the steps of delivering light into a biological system ( 12 ) containing a solute, the light having a wavelength selected to be in a range wherein the solute is substantially non-absorbing; detecting at least first and second portions of the delivered light, the first portion having traveled through the biological system along one or more paths characterized by a first average path length, and the second portion having traveled through the biological system along one or more paths characterized by a second average path length that is greater than the first average path length; and comparing the first and second portions of the delivered light to monitor concentration of the solute in the biological system. Also described are schemes for monitoring low molecular weight polyhydroxy solutes, generally sugars (mannitol, fructose, sucrose, glucose, sorbitol), alcohols (methanol, ethanol, propanediol), and electrolytes (sodium, potassium, magnesium, calcium, and chloride ions).

1 . A method for monitoring a solute in a biological system comprising the steps of: 
 delivering light into a biological system containing said solute, said light having a wavelength selected to be in a range wherein said solute is substantially non-absorbing;    detecting at least first and second portions of said delivered light, said first portion having traveled through said biological system along one or more paths characterized by a first average path length, and said second portion having traveled through said biological system along one or more paths characterized by a second average path length that is greater than said first average path length; and    comparing said first and second portions of the delivered light to monitor concentration of said solute in said biological system.    
     
     
         2 . The method of  claim 1  wherein the step of comparing said first and second portions of the delivered light comprises obtaining a characterization of said biological system based on a linear model relating an optical characteristic of said biological system and said first and second average path lengths.  
     
     
         3 . The method of  claim 2  wherein said characterization that is obtained is the slope of a line determined by fitting to said linear model measured characteristics of said first and second portions of light and distances representative of said first and second path lengths.  
     
     
         4 . The method of  claim 2  wherein said characterization that is obtained is the intercept of a line determined by fitting to said linear model measured characteristics of said first and second portions of light and distances representative of said first and second path lengths.  
     
     
         5 . The method of  claim 2  wherein said characterization that is obtained is the slope and the intercept of a line determined by fitting to said linear model measured characteristics of said first and second portions of light and distances representative of said first and second path lengths.  
     
     
         6 . The method of  claim 2  wherein obtaining a characterization comprises obtaining measures of first and second optical densities of said biological system based on said first and second portions of detected light and fitting said measures of optical densities to said generally linear model.  
     
     
         7 . The method of  claim 2  wherein the step of comparing said first and second portions of the delivered light comprises determining a measure of the concentration of one or more of said solutes based on a comparison of said characterization of said biological system against a predetermined scale.  
     
     
         8 . The method of  claim 1  further comprising the step of determining a measure of a concentration of one or more of said solutes in said biological system based on a predetermined concentration scale.  
     
     
         9 . The method of  claim 1  wherein said steps of detecting said first and second portions of said delivered light comprise measuring first and second intensities (I 1 , I 2 ) corresponding to the intensities of said first and second portions of light, respectively.  
     
     
         10 . The method of  claim 9  further comprising the step of determining changes, over time, in said first and second intensities (I 1 , I 2 ) relative to first and second reference intensities (I 1,ref , I 2,ref ).  
     
     
         11 . The method of  claim 10  wherein said step of determining relative changes in said first and second intensities further comprises respectively determining first and second optical densities (OD 1 , OD 2 ):  
       
         
           
             
               
                 OD 
                 1 
               
               = 
               
                 log 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 
                   ( 
                   
                     
                       I 
                       1 
                     
                     
                       I 
                       
                         1 
                         , 
                         ref 
                       
                     
                   
                   ) 
                 
               
             
           
         
         
           
             
               
                 OD 
                 2 
               
               = 
               
                 log 
                 ⁢ 
                 
                     
                 
                 ⁢ 
                 
                   
                     ( 
                     
                       
                         I 
                         2 
                       
                       
                         I 
                         
                           2 
                           , 
                           ref 
                         
                       
                     
                     ) 
                   
                   . 
                 
               
             
           
         
       
     
     
         12 . The method of  claim 11  wherein said step of comparing said first and second portions of the delivered light comprises using a linear model relating said first and second optical densities to distances (ρ 1 , ρ 2 ) representative of said first and second average path lengths to obtain a characterization of said biological system representative of the concentration of one or more of said solutes in said biological system.  
     
     
         13 . The method of  claim 12  wherein the characterization that is obtained is a slope (m) determined by  
       
         
           
             
               m 
               = 
               
                 
                   
                     
                       OD 
                       2 
                     
                     - 
                     
                       OD 
                       1 
                     
                   
                   
                     
                       ρ 
                       2 
                     
                     - 
                     
                       ρ 
                       1 
                     
                   
                 
                 . 
               
             
           
         
       
     
     
         14 . The method of  claim 12  wherein the characterization that is obtained is an intercept (b) determined by  
       
         
           
             
               b 
               = 
               
                 
                   
                     
                       
                         OD 
                         1 
                       
                       · 
                       
                         ρ 
                         2 
                       
                     
                     - 
                     
                       
                         OD 
                         2 
                       
                       · 
                       
                         ρ 
                         1 
                       
                     
                   
                   
                     
                       ρ 
                       2 
                     
                     - 
                     
                       ρ 
                       1 
                     
                   
                 
                 . 
               
             
           
         
       
     
     
         15 . The method of  claim 1  further comprising the step of detecting a third portion of said delivered light, said third portion having traveled through said biological system along one or more paths characterized by a third average path length that is greater than said first and second average path lengths.  
     
     
         16 . A system for monitoring a solute in a biological system comprising 
 at least two sources of light having a wavelength selected to be in a range wherein said solute is substantially non-absorbing,    a detector positioned at different distances with respect to said at least two detectors to detect at least first and second portions of said delivered light, said first portion having traveled through said biological system along one or more paths characterized by a first average path length, and said second portion having traveled through said biological system along one or more paths characterized by a second average path length that is greater than said first average path length, and    a comparator adapted to compare said first and second portions of the delivered light to monitor concentration of said solute in said biological system.    
     
     
         17 . A method of  claim 1 , wherein said solute is a low molecular weight carbohydrate, an alcohol, or an electrolyte.  
     
     
         18 . A method of  claim 17 , wherein said solute is mannitol, fructose, sucrose, glucose, propanediol, methanol, ethanol, sodium ion, potassium ion, or chloride ion.  
     
     
         19 . A method of  claim 17 , wherein said solute is sorbitol, magnesium ion, or calcium ion.  
     
     
         20 . A method of  claim 18 , wherein said solute is glucose.  
     
     
         21 . A method of  claim 18 , wherein said solute is potassium.  
     
     
         22 . A method of  claim 1 , wherein said solute is bonded to a contrast agent.