# US 2019/0170739 A1 · Electrochemical detection systems and components thereof

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- Number: US 2019/0170739 A1
- Document ID: US20190170739A1
- Status: Published application
- Kind: A1
- Application number: 16/209,649
- Filed: 2018-12-04
- Published: 2019-06-06
- Earliest claimed: 2017-12-04
- Applicants: Laxmi Therapeutic Devices, Inc.
- Inventors: Logan Earl Garner; Luke Satish Kumar Theogarajan; William Van Antwerp
- Web page: https://patentgrep.com/patent/US20190170739A1

## CPC

- G01N 33/54313: {the carrier being characterised by its particulate form}
- A61B 5/14514: {using means for aiding extraction of interstitial fluid, e.g. microneedles or suction}
- A61L 31/145: {Hydrogels or hydrocolloids}
- C08F 120/60: containing nitrogen in addition to the carbonamido nitrogen
- C08L 33/24: Homopolymers or copolymers of amides or imides
- C12Q 1/001: {Enzyme electrodes}
- C12Q 1/006: {for glucose}
- G01N 27/3273: {Devices therefor, e.g. test element readers, circuitry (details not specific to biochemical electrodes G01N33/4875)}
- G01N 27/4166: {measuring a particular property of an electrolyte}
- G01N 33/5438: {Electrodes}
- C08L 2203/02: for biomedical use
- G01N 2333/902: Oxidoreductases (1.)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- 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

The invention is directed to electrochemical detection systems, components thereof, materials and methods for making the systems and components thereof, and methods for detecting analytes with the systems. The systems include electrochemical cells containing hydrogels. The hydrogels include polymers with amine-containing pendant groups. The polymers can be cross-linked via the amine-containing pendant groups. The polymers can also or alternatively include enzymes and/or electron shuttles tethered thereto via amine-containing pendant groups. Monomers for making the polymers are provided. The systems can be used to detect analytes such as glucose.

## Claims

### Claim 1

A system comprising a polymer, wherein the polymer includes subunits of Formula I:
wherein:
R1 in each instance is independently H, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof;
R2 in each instance is independently N or O;
R3 in each instance is independently:
H; alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; or a nitrogen protecting group when R2 is N; or
absent when R2 is O;
R4 in each instance is a spacer arm;
R5 in each instance is Formula II or Formula III:
R6, R7, and R8 in each instance are independently H; alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; a nitrogen protecting group; a tethered polypeptide; a tethered redox mediator; a linking arm; or a tethered subunit of Formula I, with the proviso that at least one of R6, R7, and R8 may be absent; and
n in each instance is independently a positive integer.

### Claim 2 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered polypeptide, and the polypeptide is an oxidoreductase.

### Claim 3 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered polypeptide, and the polypeptide is a glucose oxidase.

### Claim 4 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered redox mediator, and the redox mediator comprises a compound of Formula VI:
wherein:
R12 and R13 are each independently H, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; or are fused in an aromatic or non-aromatic ring;
R14 is an electron withdrawing group;
R15 is H, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; and
the compound of Formula VI is tethered via any one or more of R12, R13, R14, R15, and any atom in the aromatic or non-aromatic ring formed by R12 and R13.

### Claim 5 (depends on 1)

The system of claim 1, wherein R14 in the electron shuttle of Formula VI is Formula VII or Formula VIII:
wherein:
REWG is an electron withdrawing group;
R16 is H, alkyl, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, perfluoroalkyl, or a combination thereof; and
R17 is a tether connected to R8.

### Claim 6 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered redox mediator, and the redox mediator is a 1,2-naphthoquinone.

### Claim 7 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered redox mediator, and the redox mediator is a 1,2-naphthoquinone comprising an electron withdrawing group connected to a 4-carbon of the 1,2-naphthoquinone.

### Claim 8 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered redox mediator, the tethered redox mediator is a 1,2-naphthoquinone comprising an electron withdrawing group connected to a 4-carbon of the 1,2-naphthoquinone, and the electron withdrawing group is selected from the group consisting of sulfonate, sulfonamide, ammonium, quaternary ammonium, fluoroaklyl, perfluoroalkyl, nitro, and cyano.

### Claim 9 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 is a tethered redox mediator, and the tethered redox mediator is a 1,2-naphthoquinone comprising a sulfonamide connected to a 4-carbon of the 1,2-naphthoquinone.

### Claim 10 (depends on 9)

The system of claim 9, wherein the 1,2-naphthoquinone is tethered via a 3-carbon, the 4-carbon, a 5-carbon, a 6-carbon, a 7-carbon, or an 8-carbon of the 1,2-naphthoquinone.

### Claim 11 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, R8 in the at least one subunit is a tethered subunit of Formula I, R5 in the tethered subunit of Formula I is Formula II, and the tethered subunit of Formula I is tethered via R8 of the tethered subunit of Formula I.

### Claim 12 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula III.

### Claim 13 (depends on 1)

The system of claim 1, wherein the spacer arm of R4 comprises one or more instances of a moiety selected from the group consisting of —(CH2)m—, —(CH2)m—O—(CH2)m—, —(CH2)m—(NR18R19)—(CH2)m—, and combinations thereof, wherein:
R18 and R19 in each instance is independently H; alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; or a nitrogen protecting group, with the proviso that at least one of R18 and R19 may be absent; and
each instance of m is independently 1-20.

### Claim 14 (depends on 1)

The system of claim 1, wherein R5 in at least one subunit of the polymer is Formula II, wherein at least one of R6, R7, and R8 in Formula II is Formula IV:
wherein R9 in each instance is independently hydrogen, alkyl, alkynyl, cycloalkyl, aryl, halogen-substituted aryl (including aryl groups substituted multiple times with the same or different halogen), nitro-substituted aryl, heterocycle, heteroaryl, hydroxyl, halo, haloalkyl, amino, an amino protected with a nitrogen protecting group, pyridine, ester, amide, azide, sulfate, sulfite, sulfoalkyl, sulfhydryl, sulfonamide, thiazole, nitro, cyano, alkoxy, carboxy, aldehyde, a saturated or unsaturated cycloalkyl, a saturated or unsaturated heterocycle, bridged saturated and unsaturated cylcoalkyl, fused aromatic, aromatic heterocycle, an N-hydroxysuccinimide ester-reactive group, an amine-reactive group, a sulfhydryl-reactive group, a tethered polypeptide, a tethered redox mediator, a linking arm; a tethered subunit of Formula I, or a combination thereof.

### Claim 15 (depends on 1)

The system of claim 1, wherein the polymer further includes subunits of Formula V:
wherein, in each instance of Formula V, R1 is H, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, or a combination thereof; n is a positive integer; and R10 is carboxyl or carboxamido.

### Claim 16 (depends on 1)

The system of claim 1, wherein the polymer is provided in the form of a hydrogel.

### Claim 17 (depends on 16)

The system of claim 16, wherein the hydrogel includes an untethered redox mediator compound.

### Claim 18 (depends on 16)

The system of claim 16, further comprising an electrode in contact with the hydrogel.

### Claim 19 (depends on 1)

A method of detecting an analyte, the method comprising contacting a sample containing the analyte with the system of claim 1, wherein:
R5 in at least one subunit is Formula II, R8 is a tethered polypeptide, and the polypeptide is an oxidoreductase; and
the detecting includes the oxidoreductase oxidizing the analyte.

### Claim 20 (depends on 19)

The method of claim 19, wherein:
R5 in at least one subunit is Formula II and R8 is a tethered redox mediator; and
the detecting includes the redox mediator undergoing a redox reaction.

### Claim 21 (depends on 19)

The method of claim 19, wherein:
the polymer is provided in the form of a hydrogel;
the system further includes an electrode in contact with the hydrogel; and
the detecting includes the electrode undergoing a change in electric charge.

### Claim 22 (depends on 19)

The method of claim 19, wherein the analyte includes glucose.