Reference electrodes having an extended lifetime for use in long term amperometric sensors
The present application provides Ag/AgCl based reference electrodes having an extended lifetime that are suitable for use in long term amperometric sensors. Electrochemical sensors equipped with reference electrodes described herein demonstrate considerable stability and extended lifetime in a variety of conditions.
1. A method of replenishing a level of AgCl on a reference electrode of a electrochemical sensor, the method comprising:
inserting a electrochemical sensor into skin of a patient, wherein the electrochemical sensor comprises a flexible substrate comprising
(i) at least one working electrode comprising a sensing layer and a membrane disposed over the sensing layer, wherein the sensing layer comprises a mediator and an analyte responsive enzyme,
(ii) at least one reference electrode comprising a layer of Ag/AgCl,
(iii) at least one contact pad coupled to each of the working and reference electrodes, wherein the electrochemical sensor is adapted for implantation of a portion of the electrochemical sensor comprising the working and reference electrodes through skin;
determining that AgCl on the reference electrode has become depleted while inserted in the patient; and
applying an electrical potential across the reference electrode and another electrode of the sensor for a period of time sufficient to convert Ag to AgCl in order to replenish the level of AgCl present on the reference electrode, wherein the electrical potential to replenish AgCl present on the reference electrode is different from the oxidation potential of the mediator.
2. The method of claim 1 , wherein said electrical potential to replenish AgCl is at least +50 mV.
3. The method of claim 1 , wherein said electrical potential to replenish AgCl is at least +100 mV.
4. The method of claim 1 , wherein said electrical potential to replenish AgCl is at least +200 mV.
5. The method of claim 1 , wherein said electrical potential to replenish AgCl is applied for a duration of at least 30 seconds.
6. The method of claim 1 , wherein said electrical potential to replenish AgCl is applied for a duration of at least 45 seconds.
7. The method of claim 1 , wherein said electrical potential to replenish AgCl is applied for a duration of at least 1 minute.
8. The method of claim 1 , wherein said application of electrical potential to replenish AgCl is repeated at least once.
9. The method of claim 1 , wherein said application of electrical potential to replenish AgCl is repeated at least twice.
10. The method according to claim 1 wherein the electrical potential to replenish AgCl present on the reference electrode is from +200 mV to +600 mV.
11. The method according to claim 10 , wherein the electrical potential to replenish AgCl present on the reference electrode is +500 mV.
12. The method according to claim 1 , wherein the oxidation potential of the mediator is from −200 mV to +200 mV.
13. The method according to claim 1 , wherein the mediator comprises osmium.
14. The method according to claim 1 , wherein determining that AgCl on the reference electrode has become depleted comprises determining that sensor output current is noisy.
15. The method according to claim 1 , wherein determining that AgCl on the reference electrode has become depleted comprises determining that no AgCl is present on the reference electrode.
16. The method according to claim 1 , wherein the method further comprises determining that the replenished level of AgCl present on the reference electrode has become depleted.
17. The method according to claim 1 , wherein determining that AgCl on the reference electrode has become depleted while inserted in the patient comprises determining that the sensor output current is noisy about 3 to 4 days after implantation.