Anti-Interferent Barrier Layers for Non-Invasive Transdermal Sampling and Analysis Device

• US 20130144142A1
• Filed: 11/29/2012
• Published: 06/06/2013
• Est. Priority Date: 12/02/2011
• Status: Active Grant

• Current Assignee: Cambridge Medical Technologies, LLC, Medina Isf Equity, LLC
• Original Assignee: Flexible Medical Systems, LLC
• Inventors: Vidalis, Joseph J., MARCANIO, Joseph A., CURRIE, John Frederick, Nadarajan, Sundar, Woodvine, Helena
• Granted Patent: US 9,968,284 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1491 Heated applicators
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/15134 Bladeless capillary blood sampling devices, i.e. devices for perforating the skin in order to obtain a blood sample but not using a blade, needle, canula, or lancet, e.g. by laser perforation, suction or pressurized fluids
• CPC Class Codes: A61B 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood

Abstract

A system and methods are provided for reducing electrochemical interference in a transdermal sampling and analysis device. A one-step transdermal glucose biosensor may calculate glucose concentrations that are artificially high compared to traditional home blood glucose sensors due to interference, which may be mitigated by forming an anti-interferent barrier layer over a sensing element. The anti-interferent barrier layer may be formed over a sensing layer and may possess a charge type which repels interferent molecules having the same charge type from interacting with the sensing layer disposed below the anti-interferent barrier layer.

Claims

1. A transdermal sampling and analysis device comprising:

a substrate having a first side;

at least one disruptor mounted on the first side of the substrate, wherein the at least one disruptor is configured to generate a localized heat capable of altering permeability characteristics of a stratum corneum layer of skin of an organism;

a reservoir configured to collect and contain a biological sample; and

a biological sensing element comprising at least two sensing electrodes configured, to determine levels of an analyte in the biological sample, wherein;

a surface of at least one of the sensing electrodes is coated with a sensing layer having a first charge type; and

the sensing layer is covered with an anti-interferent barrier layer having at least a second charge type, wherein the first charge type is an opposite charge type from the second charge type.

2. The transdermal sampling and analysis device of claim 1, wherein the sensing layer comprises an enzyme, an electron mediator, and a polymer.

3. The transdermal sampling and analysis device of claim 2, wherein the biological sample is interstitial fluid (ISF), and wherein the enzyme is an oxidoreductase.

4. The transdermal sampling and analysis device of claim 3, wherein the oxidoreductase is glucose oxidase (GOx).

5. The transdermal sampling and analysis device of claim 2, wherein:

the sensing layer comprises the polymer, wherein the polymer comprises a polycationic polymer; and

the anti-interferent barrier layer comprises a polyanionic polymer.

6. The transdermal sampling and analysis device of claim 5, wherein the polycationic polymer comprises a linear poly(ethylenimine) (LPEI).

7. The transdermal sampling and analysis device of claim 5, wherein the polyanlonic polymer comprises an alginate.

8. The transdermal sampling and analysis device of claim 1, wherein the anti-interferent barrier layer comprises:

a composite barrier layer comprising;

a first anti-interferent barrier layer having the second charge type; and

a second anti-interferent barrier layer having the first charge type, wherein the second anti-interferent barrier layer is disposed on top of the first, anti-interferent barrier layer.

9. The transdermal sampling and analysis device of claim 8, wherein the composite barrier layer comprises a plurality of alternating first anti-interferent barrier layers and second anti-interferent barrier layers.

10. The transdermal sampling and analysis device of claim 2, wherein the electron mediator is selected from the group consisting of a ferrocene, osmium bipyridine complexes, ruthenium phthalocyanine complexes, a quinone, a tetrathialfulvalene (TTF), a tetracyanoquinodimethane (TCNQ), and a thionine.

11. The transdermal sampling and analysis device of claim 8, wherein the first anti-interferent barrier layer comprises alginate.

13. The transdermal sampling and analysts device of claim 11, wherein the alginate comprises a salt of alginic acid that is less than 200 kDa.

14. The transdermal sampling and analysis device of claim 13, wherein the alginate comprises a salt of alginic acid that is less than 75 kDa,

12. The transdermal sampling and analysis device of claim S, wherein the first anti-interferent barrier layer comprises an alginate monolayer;

and

the second anti-interferent barrier layer comprises chitosan.

15. A transdermal sampling and analysis device comprising:

a substrate having a first side;

at least one disruptor mounted on the first side of the substrate, wherein the at least one disruptor is configured to generate a localized heat capable of altering permeability characteristics of a stratum corneum layer of skin of an organism;

a reservoir configured to collect, and contain a biological sample; and

a biological sensing element comprising at least two sensing electrodes configured to determine levels of an analyte in the biological sample, wherein;

a surface of at least one of the sensing electrodes is coated with a sensing layer; and

the sensing layer is covered with an anti-interferent barrier layer, wherein molecules of the anti-interferent barrier layer are conjugated to molecules of the sensing layer.

16. The transdermal sampling and analysis device of claim 15, wherein the sensing layer comprises an enzyme, an electron mediator, and a polymer.

17. The transdermal sampling and analysis device of claim 16, wherein the biological sample is interstitial fluid (ISF), and wherein the enzyme is an oxidoreductase.

18. The transdermal sampling and analysis device of claim 17, wherein the oxidoreductase is glucose oxidase (GOx).

19. The transdermal sampling and analysts device of claim 16, wherein the polymer comprises a linear poly(ethylenimine) (LPEI), and wherein the molecules of the anti-interferent barrier layer are conjugated to amine groups of the LPEI.

20. The transdermal sampling and analysis device of claim 15, wherein the sensing layer is uncharged.

21. The transdermal sampling and analysis device of claim 15, wherein the anti-interferent barrier layer has a charge type.

22. The transdermal sampling and analysis device of claim 21, wherein the anti-interferent barrier layer is a polyanionic polymer.

23. The transdermal sampling and analysis device of claim 21, wherein the anti-interferent barrier layer is a polycationic polymer.

24. The transdermal sampling and analysis device of claim 15, wherein the anti-interferent barrier layer comprises;

a composite barrier layer comprising;

a first anti-interferent barrier layer having a first charge type, wherein molecules of the first anti-interferent barrier layer are conjugated to molecules of tire sensing layer; and

a second anti-interferent barrier layer having a second charge type, wherein the second anti-interferent barrier layer is disposed on top of the first anti-interferent barrier layer and bound to the first anti-interferent barrier layer through charge interaction.

25. The transdermal sampling and analysis device of claim 24, wherein the composite barrier layer comprises a plurality of alternating first anti-interferent barrier layers and second anti-interferent barrier layers, wherein molecules of an initial first anti-interferent layer are conjugated to molecules of the sensing layer.

26. The transdermal sampling and analysis device of claim 16, wherein the electron mediator is selected from the group consisting of a ferrocene, osmium bipyridine complexes, ruthenium phthalocyanine complexes, a quinone, a tetrathialfulvalene (TTF), a tetracyanoquinodimethane (TCNQ), and a thionine.

27. A transdermal sampling and analysis device comprising:

a substrate having a first side;

at least one disruptor mounted on the first side of the substrate, wherein the at least one disruptor is configured to generate a localized heat, capable of altering permeability characteristics of a stratum corneum layer of skin of an organism;

a reservoir configured to collect and contain a biological sample; and

a biological sensing element comprising at least two sensing electrodes configured to determine levels of an analyte in the biological sample, wherein;

a surface of at least one of the sensing electrodes is coated with a sensing layer, wherein the sensing layer has an electron mediator; and

the sensing layer is covered with an anti-interferent barrier layer, wherein the anti-interferent barrier layer has a charge type to repel a charged biological reducing species in the biological sample from interacting with the electron mediator.

28. The transdermal sampling and analysis device of claim 27, wherein the sensing layer further comprises an enzyme and a polymer.

29. The transdermal sampling and analysis device of claim 28, wherein the biological sample is interstitial fluid (ISF), and wherein the enzyme is an oxidoreductase.

30. The transdermal sampling and analysts device of claim 29, wherein the oxidoreductase is glucose oxidase (GOx).

31. The transdermal sampling and analysis device of claim 27, wherein the sensing layer has a second charge type and the anti-interferent barrier layer is attracted to the sensing layer through charge interaction.

32. The transdermal sampling and analysis device of claim 27, wherein the anti-interferent barrier layer is conjugated to the sensing layer.

33. The transdermal sampling and analysis device of claim 27, wherein the anti-interferent barrier layer is held to the sensing layer through van der Waals forces.

38. The method of claim 31, wherein the anti-interferent barrier layer is conjugated to the sensing layer.

34. A method of preventing interference from a charged biological reducing species in a transdermal biosensor device, comprising:

creating a solid state sensor wherein an enzyme and an electron mediator are immobilized by a polymer to form a sensing layer, wherein the polymer is anchored to a sensing electrode; and

applying an anti-interferent barrier layer atop the sensing layer, wherein charge type repulsion between the anti-interferent barrier layer and the charged biological reducing species prevents interaction between the charged biological reducing species and the electron mediator.

35. The method of claim 34, wherein the anti-interferent barrier layer is associated with the sensing layer via charge interaction.

36. The method of claim 34, wherein applying the anti-interferent barrier layer atop the sensing layer comprises applying a composite barrier layer atop the sensing layer, wherein the composite barrier layer comprises:

a first anti-interferent barrier layer having a first charge type, wherein the first anti-interferent barrier layer is associated with the sensing layer via charge interaction; and

a second anti-interferent barrier layer having a second charge type, wherein the second anti-interferent barrier layer is disposed on top of the first anti-interferent barrier layer.

37. The method of claim 36, wherein applying the composite barrier layer atop the sensing layer comprises:

applying an initial first anti-interferent barrier layer atop the sensing layer; and

applying a plurality of alternating second anti-interferent barrier layers and first anti-interferent barrier layers atop the initial first anti-interferent barrier layer.