POLYMER MEMBRANES FOR CONTINUOUS ANALYTE SENSORS

• US 20130053665A1
• Filed: 08/24/2012
• Published: 02/28/2013
• Est. Priority Date: 08/26/2011
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Hughes, Jonathan, Boock, Robert J., Dring, Chris W.
• Granted Patent: US 9,549,692 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/333 Ion-selective electrodes or membranes glass electrodes G01N27/36

Abstract

Devices and methods are described for providing continuous measurement of an analyte concentration. In some embodiments, the devices include a membrane that has an interference domain designed to reduce the permeation of one or more interferents.

Claims

1. An implantable device for continuous measurement of an analyte concentration, the implantable device comprising:

a sensor configured to generate a signal indicative of a concentration of an analyte in a host; and

a membrane located over the sensor, the membrane comprising a first domain configured to reduce a flux therethrough of the analyte, a second domain that comprises an enzyme, and a third domain configured to reduce passage therethrough of an interferent, the third domain comprising a plurality of alternating polyelectrolyte layers.

2. The implantable device of claim 1, wherein the plurality of alternating polyelectrolyte layers of the third domain comprise two types of layers.

3. The implantable device of claim 2, wherein the two types of layers comprise a polycationic layer and a polyanionic layer.

4. The implantable device of claim 3, wherein polycationic layers form the most distal layer and the most proximal layer of the third domain with respect to the sensor.

5. The implantable device of claim 4, wherein the third domain comprises an odd number of alternating polyelectrolyte layers.

6. The implantable device of claim 5, wherein the third domain comprises at least three alternating polyelectrolyte layers.

7. The implantable device of claim 6, wherein the first and third most distal layers with respect to the sensor are polycationic layers, and wherein the second most distal layer with respect to the sensor is a polyanionic layer.

8. The implantable device of claim 5, wherein the third domain comprises at least five alternating polyelectrolyte layers.

9. The implantable device of claim 8, wherein the first, third, and fifth most distal layers with respect to the sensor are polycationic layers, and wherein the second and fourth most distal layers with respect to the sensor are polyanionic layers.

10. The implantable device of claim 5, wherein the third domain comprises at least seven alternating polyelectrolyte layers.

11. The implantable device of claim 10, wherein the first, third, fifth, and seventh most distal layers with respect to the sensor are polycationic layers, and the second, fourth, and sixth most distal layers with respect to the sensor are polyanionic layers.

12. The implantable device of claim 2, wherein the two types of layers comprise a first layer type configured to selectively reduce passage therethrough of a first interferent and a second layer type configured to selectively reduce passage therethrough of a second interferent.

13. The implantable device of claim 1, wherein the plurality of alternating polyelectrolyte layers comprise at least three types of layers or bilayers.

14. The implantable device of claim 13, wherein the at least three types of layers or bilayers comprises a first layer or first bilayer type configured to selectively reduce passage therethrough of a first interferent, a second layer or second bilayer type configured to selectively reduce passage therethrough of a second interferent, and a third layer or third bilayer type configured to selectively reduce passage therethrough of a third interferent.

15. The implantable device of claim 1, wherein the first domain is distal to the second domain with respect to the sensor, and wherein the second domain is distal to the third domain with respect to the sensor.

16. The implantable device of claim 1, wherein the sensor comprises an electroactive surface, and wherein the third domain contacts the electroactive surface.

17. An implantable device for continuous measurement of glucose concentration, the device comprising:

an electrode configured to generate a signal indicative of a concentration of glucose in a host; and

a membrane located over the electrode, the membrane comprising;

a first domain that comprises an enzyme configured to react with glucose and produce hydrogen peroxide;

a second domain configured to reduce passage therethrough of an interferent, the second domain comprising a plurality of alternating polyelectrolyte layers, wherein the plurality of alternating polyelectrolyte layers comprise at least one of a polycationic layer and a polyanionic layer, whereby the device is configured to exhibit a selectivity for acetaminophen over hydrogen peroxide of less than about 0.5, wherein the selectivity is determined by dividing a sensitivity of the device for acetaminophen by a sensitivity of the device for hydrogen peroxide, wherein the acetaminophen sensitivity is determined in vitro by measuring the device'"'"'s current response versus concentrations of acetaminophen at 10 μ

M aqueous acetaminophen, 50 μ

M aqueous acetaminophen, and 100 μ

M aqueous acetaminophen, and then performing linear regression, and wherein the hydrogen peroxide sensitivity is determined in vitro by measuring the device'"'"'s current response versus concentrations of hydrogen peroxide at 1 μ

M aqueous hydrogen peroxide, 2 μ

M aqueous hydrogen peroxide, and 3 μ

M aqueous hydrogen peroxide, and then performing linear regression.

18. The implantable device of claim 17, wherein the electrode comprises an electroactive surface.

19. The implantable device of claim 18, wherein the second domain contacts the electroactive surface.

20. The implantable device of claim 17, wherein the membrane further comprises a third domain configured to reduce a flux therethrough of glucose.

21. The implantable device of claim 17, wherein the device is configured to exhibit a selectivity for acetaminophen over hydrogen peroxide of less than about 0.047.

22. The implantable device of claim 17, wherein the device is configured to exhibit a selectivity for acetaminophen over hydrogen peroxide of less than about 0.013.

23. The implantable device of claim 17, wherein the device is configured to exhibit a selectivity for acetaminophen over hydrogen peroxide of less than about 0.006.

24. The implantable device of claim 17, wherein the polycationic layer comprises a polycation with an average linear charge density from about 2 to 10 e/Å

, and wherein the polyanionic layer comprises a polyanion with an average linear charge density from about 2 to 10 e/Å

.

25. The implantable device of claim 17, wherein the polycationic layer comprises a polycation with an average linear charge density from about 2 to 3 e/Å

, and wherein the polyanionic layer comprises a polyanion with an average linear charge density from about 2 to 3 e/Å

.