# US 11,432,750 B2 · In vivo enzyme activity sensors and methods

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- Number: US 11,432,750 B2
- Document ID: US11432750B2
- Status: Granted
- Kind: B2
- Application number: 15/457,896
- Filed: 2017-03-13
- Published: 2017-09-14
- Granted: 2022-09-06
- Earliest claimed: 2016-03-14
- Assignees: Abbott Diabetes Care Inc.
- Applicants: Abbott Diabetes Care, Inc.
- Inventors: Mark Eshoo; Benjamin Feldman; Tianmei Ouyang; Lam Tran
- Web page: https://patentgrep.com/patent/US11432750B2

## CPC

- A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes}
- A61B 5/1473: invasive, e.g. introduced into the body by a catheter
- A61B 5/14735: {comprising an immobilised reagent}
- A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors}
- A61B 5/411: {Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance}
- A61B 5/7278: {Artificial waveform generation or derivation, e.g. synthesizing signals from measured signals}
- C12Q 1/004: {mediator-assisted}
- C12Q 1/005: {involving specific analytes or enzymes (including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence)}
- C12Q 1/46: involving cholinesterase
- A61B 2505/01: Emergency care
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

In vivo monitoring devices and systems for enzymes and/or analytes including devices having a reactant reservoir are provided.

## Claims

### Claim 1

A continuous in vivo apparatus for determining the activity of an enzyme in vivo, comprising:
a detection device comprising one or more working electrodes;
a reaction area comprising the enzyme, the reaction area in fluid communication with the detection device and placed in contact with the one or more working electrodes;
a storage reservoir containing a predetermined quantity of a reactant;
at least one aperture passing through the one or more working electrodes, wherein the at least one aperture connects the storage reservoir to the reaction area proximate to a surface of the one or more working electrodes;
wherein the storage reservoir passively provides the reactant to the reaction area only through egress from the at least one aperture;
wherein the one or more working electrodes are configured to detect a product of a reaction of the reactant and the enzyme in the reaction area; and
wherein at least a portion of the reaction area and the storage reservoir are implantable into a tissue.

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein the reactant is acetylthiocholine and the enzyme is acetylcholinesterase.

### Claim 3 (depends on 1)

The apparatus of claim 1, wherein at least a portion of the storage reservoir is formed on or within a support layer.

### Claim 4 (depends on 3)

The apparatus of claim 3, wherein the at least one aperture further passes through the support layer.

### Claim 5 (depends on 1)

The apparatus of claim 1, wherein the at least one aperture further comprises a regulator to control a release of the reactant from the storage reservoir over a predetermined period of time.

### Claim 6 (depends on 5)

The apparatus of claim 5, wherein the regulator is a membrane.

### Claim 7 (depends on 1)

The apparatus of claim 1, wherein the reaction area further comprises a polymer layer containing the enzyme.

### Claim 8 (depends on 7)

The apparatus of claim 7, wherein the enzyme is crosslinked to the polymer layer.

### Claim 9 (depends on 8)

The apparatus of claim 8, wherein the polymer layer comprises a redox polymer.

### Claim 10 (depends on 9)

The apparatus of claim 9, wherein the redox polymer is an osmium redox polymer.

### Claim 11 (depends on 10)

The apparatus of claim 10, wherein the osmium redox polymer is osmium poly(4-vinyl pyridine).

### Claim 12 (depends on 1)

The apparatus of claim 1, wherein the enzyme within the reaction area is immobilized to the one or more working electrodes.

### Claim 13

A continuous in vivo apparatus for determining the activity of an enzyme in vivo, comprising:
a storage reservoir containing a predetermined quantity of a reactant;
a working electrode comprising at least one aperture; and
a reaction layer arranged on the working electrode, wherein the reaction layer comprises an enzyme;
wherein the reactant is passively released from the storage reservoir through the at least one aperture of the working electrode, wherein the working electrode is configured to detect a product of a reaction of the reactant with the enzyme in the reaction layer in order to produce a signal proportional to the activity of the enzyme, and
wherein at least a portion of the apparatus is configured to be positioned beneath a skin surface.

### Claim 14 (depends on 13)

The apparatus of claim 13, wherein the reaction layer comprises a polymer layer containing the enzyme.

### Claim 15 (depends on 13)

The apparatus of claim 13, wherein the reaction layer further comprises an electron transfer agent.

### Claim 16 (depends on 13)

The apparatus of claim 13, wherein a support layer defines at least a portion of the storage reservoir.

### Claim 17

A continuous in vivo apparatus for determining the activity of an enzyme in vivo, comprising:
a working electrode comprising at least one aperture;
a storage reservoir containing a predetermined quantity of a reactant, wherein the storage reservoir is arranged on a first side of the working electrode; and
a reaction layer comprising an enzyme, wherein the reaction layer is arranged on an opposing, second side of the working electrode,
wherein the reactant is configured to be passively released through the at least one aperture of the working electrode such that the reactant reacts with the enzyme in the reaction layer, and wherein the working electrode is configured to detect a product of a reaction of the reactant and the enzyme in the reaction layer.

### Claim 18 (depends on 17)

The apparatus of claim 17, wherein at least a portion of the apparatus is configured to be positioned beneath a skin surface.

### Claim 19 (depends on 17)

The apparatus of claim 17, further comprising a support layer defining at least a portion of the storage reservoir.

### Claim 20 (depends on 17)

The apparatus of claim 17, wherein the reaction layer further comprises an electron transfer agent.
