Analyte monitoring: stabilizer for subcutaneous glucose sensor with incorporated antiglycolytic agent

Abstract

An analyte sensor including an antiglycolytic agent or a precursor thereof and a chelating agent that stabilizes the antiglycolytic agent positioned proximate to the working electrode of the sensor. Also provided are systems and methods of using the electrochemical analyte sensors in analyte monitoring.

1 . An analyte sensor comprising:
 a) a working electrode comprising a sensing layer disposed thereon; and   b) a mass transport limiting membrane disposed over the sensing layer, the mass transport limiting membrane comprising an antiglycolytic agent and a chelating agent, wherein the chelating agent stabilizes the antiglycolytic agent.   
     
     
         2 . The sensor of  claim 1 , wherein the sensing layer comprises a glucose responsive enzyme. 
     
     
         3 . The sensor of  claim 1 , wherein the antiglycolytic agent is selected from the group consisting of D-glyceraldehyde, L-glyceraldehyde, mannose, glucosamine, mannoheptulose, sorbose-6-phosphate, trehalose-6-phosphate, maleimide, iodoacetates, fluorides, and combinations thereof. 
     
     
         4 . The sensor of  claim 1 , wherein the antiglycolytic agent is a racemic mixture of D- and L-glyceraldehyde. 
     
     
         5 . The sensor of  claim 1 , wherein the antiglycolytic agent is a glyceraldehyde. 
     
     
         6 . The sensor of  claim 1 , wherein the chelating agent is selected from the group consisting of borate, boric acid, main group metals, transition metals, Group IIIA metals, and combinations thereof. 
     
     
         7 . The sensor of  claim 6 , wherein the chelating agent is boric acid. 
     
     
         8 . The sensor of  claim 5 , wherein the glyceraldehyde is present in an amount ranging from about 1 microgram to about 2 milligrams. 
     
     
         9 . The sensor of  claim 7 , wherein the boric acid is present in an amount ranging from about 1 microgram to about 2 milligrams. 
     
     
         10 . The sensor of  claim 1 , wherein the membrane has a thickness ranging from about 0.1 microns to about 100 microns. 
     
     
         11 . The sensor of  claim 1 , wherein the sensing layer further comprises an electron transfer agent. 
     
     
         12 . The sensor of  claim 1 , wherein the antiglycolytic agent is chemically bonded to the chelating agent. 
     
     
         13 . The sensor of  claim 1 , further comprising a counter electrode, wherein the sensing layer comprises a glucose responsive enzyme, and the sensor is a glucose sensor. 
     
     
         14 . An analyte sensor comprising:
 a) a working electrode comprising a sensing layer disposed thereon, the sensing layer comprising an antiglycolytic agent and a chelating agent that stabilizes the antiglycolytic agent; and   b) a counter electrode.   
     
     
         15 . The sensor of  claim 14 , wherein the sensing layer comprises a glucose responsive enzyme. 
     
     
         16 . The sensor of  claim 14 , wherein the antiglycolytic agent is selected from the group consisting of D-glyceraldehyde, L-glyceraldehyde, mannose, glucosamine, mannoheptulose, sorbose-6-phosphate, trehalose-6-phosphate, maleimide, iodoacetates, fluorides, and combinations thereof. 
     
     
         17 . The sensor of  claim 14 , wherein the antiglycolytic agent is a racemic mixture of D- and L-glyceraldehyde. 
     
     
         18 . The sensor of  claim 14 , wherein the antiglycolytic agent is a glyceraldehyde. 
     
     
         19 . The sensor of  claim 14 , wherein the chelating agent is selected from the group consisting of borate, boric acid, main group metals, transition metals, Group IIIA metals, and combinations thereof. 
     
     
         20 . The sensor of  claim 19 , wherein the chelating agent is boric acid. 
     
     
         21 . The sensor of  claim 18 , wherein the glyceraldehyde is present in an amount ranging from about 1 microgram to about 2 milligrams. 
     
     
         22 . The sensor of  claim 20 , wherein the boric acid is present in an amount ranging from about 1 microgram to about 2 milligrams. 
     
     
         23 . The sensor of  claim 14 , wherein the sensing layer further comprises an electron transfer agent. 
     
     
         24 . An analyte sensor comprising:
 a) a working electrode comprising a sensing layer disposed thereon; and   b) a mass transport limiting membrane surrounding the sensing layer, the mass transport limiting membrane comprising an antiglycolytic agent and a chelating agent, wherein the chelating agent stabilizes the antiglycolytic agent.   
     
     
         25 . The sensor of  claim 24 , wherein the sensing layer comprises a glucose responsive enzyme. 
     
     
         26 . The sensor of  claim 24 , wherein the antiglycolytic agent is selected from the group consisting of D-glyceraldehyde, L-glyceraldehyde, mannose, glucosamine, mannoheptulose, sorbose-6-phosphate, trehalose-6-phosphate, maleimide, iodoacetates, fluorides, and combinations thereof. 
     
     
         27 . The sensor of  claim 24 , wherein the antiglycolytic agent is a racemic mixture of D- and L-glyceraldehyde. 
     
     
         28 . The sensor of  claim 24 , wherein the antiglycolytic agent is a glyceraldehyde. 
     
     
         29 . The sensor of  claim 24 , wherein the chelating agent is selected from the group consisting of borate, boric acid, main group metals, transition metals, Group IIIA metals, and combinations thereof. 
     
     
         30 . The sensor of  claim 29 , wherein the chelating agent is boric acid. 
     
     
         31 . The sensor of  claim 24 , further comprising a counter electrode, wherein the sensing layer comprises a glucose responsive enzyme, and the sensor is a glucose sensor.