Analyte test system for determining the concentration of an analyte in a physiological or aqueous fluid

Abstract

An analyte test element for determining the concentration of at least one analyte in a physiological sample fluid having a first and a second surface in a predetermined distance opposite from each other, said both surfaces are provided with two substantially equivalent patterns forming areas of high and low surface energy which are aligned mostly congruent, whereby the areas with high surface energy create a sample distribution system with at least two detection areas, characterized in that the detection areas of first and second surface are also provided with two corresponding patterns of working and reference electrodes of electrochemical detection means.

1 . An analyte test element for determining the concentration of at least one analyte in a physiological or aqueous sample fluid having a first surface ( 2   a ) and a second surface ( 4   a ) in a predetermined distance opposite from each other, said first and second surfaces are provided with two substantially equivalent patterns, forming areas of high and low surface energy, which are aligned most congruent, whereby the areas of high surface energy ( 6 ,  6 ′) create a sample distribution system with at least two detection areas ( 6   a ,  6 ′ a ), characterized in that the detection areas ( 6   a ) of the first surface ( 2   a ) are provided with working electrodes ( 8   a ) and the detection areas ( 6 ′ a ) of the second surface ( 4   a ) are provided with corresponding reference electrodes ( 8 ′ a ) of electrochemical detection means. 
     
     
         2 . The analyte test element according to  claim 1 , wherein the distance between the first and second surface is determined by a center layer ( 3 ), which is arranged between a base layer ( 2 ) and a cover layer ( 4 ) having the first and second surfaces ( 2   a ,  4   a ). 
     
     
         3 . The analyte test element according to  claim 2 , wherein the center layer ( 3 ) has a discontinuity ( 5 ) to form a hollow cavity together with the first and second surface ( 2   a ,  4   a ) of the base and cover layer ( 2 ,  4 ), said hollow cavity being larger than the sample distribution system formed by the areas of high surface energy ( 6 ,  6 ′) on the first and second surfaces ( 2   a ,  4   a ). 
     
     
         4 . The analyte test element according to  claim 1 , wherein said areas of high surface energy ( 6 ,  6 ′) are created by a water insoluble hydrophilic composition applied on the first and second surfaces ( 2   a ,  4   a ). 
     
     
         5 . The analyte test element according to  claim 1 , wherein said areas of high surface energy ( 6 ,  6 ′) on first and second surfaces ( 2   a ,  4   a ) are restricted by hydrophobic insulating layers ( 14 ,  14 ′) providing areas with low surface energy. 
     
     
         6 . The analyte test element according to  claim 1 , wherein
 n predetermined detection areas ( 6   a ) covering the working electrodes ( 8   a ) of said first surface ( 2   a ) are coated with a catalytic formulation promoting the electrochemical detection of an analyte in a physiological fluid, and   n predetermined detection areas ( 6 ′ a ) covering the reference electrodes ( 8 ′ a ) of said second surface ( 4   a ) are coated with n calibration formulations made up of m blank formulations and n−m formulations with different levels of calibration compound, whereby n is an integer number larger than 2, m is an integer number equal or larger than 1, and n>m.   
     
     
         7 . The analyte test element according to  claim 6 , wherein an additional detection area ( 6   c ) is provided, which neither contains the catalytic compound nor the calibration compound, enabling the measurement of background signals. 
     
     
         8 . The analyte test element according to  claim 6 , wherein said calibration compound contained in the calibration formulation coated on n−m predetermined detection areas ( 6 ′ a ) of second surface ( 4   a ) is identical or substantially equivalent to the analyte and able to induce the same chemical reaction in the catalytic formulation as the analyte in physiological fluid sample. 
     
     
         9 . The analyte test element according to  claim 8 , wherein the calibration compound is glucose. 
     
     
         10 . The analyte test element according to  claim 6 , wherein the catalytic formulation contains as reactive components a promoter undergoing a catalytic or non catalytic reaction with the analyte, and/or a co-enzyme, and a mediator generating an electrochemical signal at the surface of an electrode. 
     
     
         11 . The analyte test element according to  claim 10 , wherein the promoter is an enzyme selected from the group consisting of dehydrogenases, kinases, oxidases, phosphatases, reductases and/or transferases. 
     
     
         12 . The analyte test element according to  claim 11 , wherein the promoter is an enzyme specific for glucose. 
     
     
         13 . The analyte test element according to  claim 10 , wherein the mediator to determine the analyte concentration is selected from the group consisting of potassium hexacyanoferrate (III), tetracyano-p-quinone-di-methane (TCNQ), methylviologen (MV2 + ), tetrathiafulavlene (TTF), N-methylphenzinium (NMP + ), ruthenium (III) hexamine, osmium bipyridine, ferrocene or their derivates. 
     
     
         14 . The analyte test element according to  claim 1 , which is provided in form of a strip, wherein a sample application area ( 9 ) is located at the end of a convex and lateral extension ( 10 ) on one side of said analyte test strip. 
     
     
         15 . An analyte test arrangement including a plurality of analyte test elements according to  claim 1 , which are arranged symmetrically around a center point to form an analyte test disk ( 29 ) with outward facing sample application areas ( 9 ). 
     
     
         16 . An analyte test arrangement including a plurality of elements according to  claim 1 , which are arranged in a linear manner to form an analyte test bandolier ( 43 ) with lateral extensions forming the sample application areas ( 9 ). 
     
     
         17 . A method for preparing an analyte test element comprising the steps:
 applying a pattern of working electrodes ( 8 ) on a first layer ( 2 ) having a first surface ( 2   a ),   applying a corresponding pattern of reference electrodes ( 8 ′) on a second layer ( 4 ) having a second surface ( 4   a ),   generating areas of high and low surface energy on the first surface ( 2   a ),   generating corresponding pattern of areas of high and low surface energy on the second surface ( 4   a ), the areas of high surface energy ( 6 ,  6 ′) forming a hydrophilic sample distribution system with n predetermined detection areas ( 6   a ,  6 ′ a ), whereby n is an integer number larger than 2, whereby the working and reference electrodes ( 8 ,  8 ′) are located underneath a predetermined detection areas ( 6 ,  6 ′) of the hydrophilic sample distribution system,   coating a catalytic formulation on then detection areas ( 6   a ) of the first surface, said catalytic formulation promoting the detection of an analyte concentration contained in a physiological fluid sample using electrochemical detection means,   coating n calibration formulations on n detection areas ( 6 ′ a ) of the second surface, said n calibration formulations made up of m blank formulations and n−m formulations with different levels of calibration compound, whereby m is an integer number of at least 1, and n>m, which is identical or substantially equivalent to the analyte and able to induce the same chemical reaction in the catalytic formulation as the analyte in the physiological fluid sample,   applying the layers of first and second surfaces to the opposite sites of a center layer ( 3 ) having a discontinuity ( 5 ), which provides a cavity for the sample distribution system formed by the areas of high surface energy ( 6 ,  6 ′) on the first and second surfaces ( 2   a ,  4   a ) of the first and second layer ( 2 ,  4 ).   
     
     
         18 . A method for preparing an analyte test element according to  claim 17 , wherein said areas of high surface energy ( 6 ,  6 ′) are created by applying a water insoluble hydrophilic composition on the first and second surfaces ( 2   a ,  4   a ). 
     
     
         19 . A method for preparing an analyte test element according to  claim 17 , wherein said areas of low surface energy are created by applying hydrophobic compositions on the first and second surfaces ( 2   a ,  4   a ) forming electrically insulating layers ( 14 ,  14 ′), which surround the areas of high surface energy ( 6 ,  6 ′). 
     
     
         20 . A method of preparing an analyte test element according to  claim 18 , wherein said hydrophilic compositions are printed on the first and second surface by the means of flexography, lithograph, gravure, solid ink coating methods, or ink-jet-printing. 
     
     
         21 . A method for preparing an analyte test element according to  claim 17 , wherein said catalytic and/or calibration compositions are coated on the detection areas ( 6   a ,  6 ′ a ) of first and second surface by ink-jet-printing or micro-dispensing. 
     
     
         22 . A method for preparing an analyte test element according to  claim 17 , wherein the first layer ( 2 ) and the second layer ( 4 ) are formed from one flexible substrate and folded along a longitudinal centered fold line ( 45 ) to enclose the center layer ( 3 ) in a manner that the hydrophilic patterns ( 6 ,  6 ′) forming the sample distribution system with the predetermined detection areas ( 6 ′ a ,  6   a ) and the corresponding working and reference electrodes ( 8 ,  8 ′) of said first surface ( 2   a ) and second surface ( 4   a ) are aligned and registered to be mostly congruent. 
     
     
         23 . An analyte test system for determining the concentration of an analyte in a physiological or aqueous sample fluid comprising:
 an analyte test element according to  claim 1 , wherein a predetermined detection areas ( 6   a ) of a first surface ( 2   a ) are coated with a catalytic formulation promoting the detection of an analyte in a physiological fluid, and   n predetermined detection areas ( 6 ′ a ) of a second surface ( 4   a ) are coated with calibration formulations made up of m blank formulations and n−m formulations with different levels of calibration compound, whereby n is an integer number larger than 2, m is an integer number equal or larger than 1, and n>m,   electrochemical detection means for detecting an electrochemical signal of the physiological sample located in 2n predetermined detection areas and obtaining a results from 2n predetermined detection areas, and   processing means for calculating all calibration coefficients of a polynomial calibration equation available from the n measurements obeying,   
       
         
           
             
               
                 y 
                 = 
                 
                   
                     ∑ 
                     l 
                     
                       n 
                       - 
                       1 
                     
                   
                    
                   
                     { 
                     
                       
                         c 
                         
                           ( 
                           
                             n 
                             - 
                             1 
                           
                           ) 
                         
                       
                        
                       
                         x 
                         
                           ( 
                           
                             n 
                             - 
                             1 
                           
                           ) 
                         
                       
                     
                     } 
                   
                 
               
               , 
             
           
         
       
       and one regression coefficient to validate the quality of the calculated calibration coefficients of the calibration equation. 
     
     
         24 . A method for determining the concentration of at least one analyte in a physiological or aqueous sample, said method comprising:
 connecting an analyte test element to a detection and processing means,   applying a physiological sample to an analyte test element having a first surface ( 2   a ) and a second surface ( 4   a ) in a predetermined distance opposite from each other, said both surfaces are provided with tow substantially equivalent patterns ( 6 ,  6 ′) forming areas of high surface energy which are aligned mostly congruent to create a sample distribution system with at least two detection areas ( 6   a ) each of them overlaying a working electrode ( 8 ), and at least two detection areas ( 6 ′ a ), each of them overlaying a reference electrode ( 8 ′ a ),   detecting the signals produced in the different detection areas, and   relating the signals to determine the amount of the analyte(s) in the physiological sample.   
     
     
         25 . An analyte test element for determining the concentration of at least one analyte in a physiological or aqueous sample fluid having a first surface and a second surface in a predetermined distance opposite from each other, wherein one of the first and second surface is provided with a hydrophilic or hydrophobic pattern and the corresponding surface provides a homogeneous pattern of hydrophilic pixels surrounded by a hydrophobic area therefore creating a surface with semi hydrophilic and semi hydrophobic character, whereby the hydrophilic and semi hydrophilic areas create a sample distribution system with at least two detection areas, said detection areas of the first surface are provided with working electrodes and the detection areas of the second surface are provided with corresponding reference electrodes ( 8 ′ a ) of electrochemical detection means. 
     
     
         26 . A method for preparing an analyte test element according to  claim 19 , wherein said hydrophobic compositions are printed on the first and second surface by the means of flexography, lithograph, gravure, solid ink coating methods, or ink-jet printing.