Measurement of glucose in an insulin delivery catheter by minimizing the adverse effects of insulin preservatives

A device for delivery of an insulin or insulin analog formulation and measurement of subcutaneous glucose concentration, comprising:

• a hollow tube comprising a proximal end and a distal end, wherein the proximal end is in fluid communication with a source of the insulin or insulin analog formulation, wherein the distal end is configured to deliver the insulin or insulin analog formulation subcutaneously, wherein the insulin or insulin analog formulation comprises an excipient comprising a phenol or cresol;
• and
• an amperometric glucose sensor located no more than 7 millimeters (mm) away from the distal end, wherein the amperometric glucose sensor comprises:
• an electrode layer comprising at least one indicating electrode, wherein the electrode layer underlies a redox-catalytic layer comprising (1) an osmium-based redox mediator comprising an osmium compound covalently bound to a pyridine-based or imidazole-based ligand, and (2) an enzyme comprising glucose oxidase or glucose dehydrogenase,
• wherein the osmium-based redox mediator and the enzyme allow electron transfer from subcutaneous glucose to the at least one indicating electrode sufficient to cause a response of the amperometric glucose sensor to a subcutaneous glucose concentration at an applied bias potential of no more than +250 millivolts (mV) relative to a reference electrode, and
• wherein the applied bias potential of no more than +250 mV relative to the reference electrode allows the electrode layer to undergo substantially no electropolymerization of the excipient during continuous operation of at least one hour of the amperometric glucose sensor, thereby maintaining a sensitivity of the amperometric glucose sensor to the subcutaneous glucose concentration in presence of the insulin or insulin analog formulation.