# US 12,181,470 B2 · Regenerable affinity sensors and associated methods

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- Number: US 12,181,470 B2
- Document ID: US12181470B2
- Status: Granted
- Kind: B2
- Application number: 17/481,806
- Filed: 2021-09-22
- Published: 2023-03-30
- Granted: 2024-12-31
- Earliest claimed: 2021-09-22
- Assignees: Xerox Corporation
- Applicants: Palo Alto Research Center Incorporated
- Inventors: Sean Doris; Anne Plochowietz; Jerome Unidad
- Web page: https://patentgrep.com/patent/US12181470B2

## CPC

- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- G01N 33/84: involving inorganic compounds or pH
- 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)

## Abstract

Affinity sensors may exhibit advantaged regeneration behavior when pH is changed in proximity to a sensing element. Such affinity sensors may comprise at least one sensing element comprising a recognition moiety that interacts with an analyte by reversibly forming an analyte complex, and a solid-state pH-modulating element in proximity to the at least one sensing element, wherein formation of the analyte complex is pH-dependent and the at least one sensing element provides a signal that changes when the analyte complex reversibly forms, and a change in magnitude of the signal is correlatable to an amount of analyte interacted with the at least one sensing element.

## Claims

### Claim 1

An affinity sensor comprising:
at least one sensing element comprising a recognition moiety that interacts with an analyte by reversibly forming an analyte complex;
wherein formation of the analyte complex is pH-dependent; and
wherein the at least one sensing element provides a signal that changes when the analyte complex reversibly forms, and a change in magnitude of the signal is correlatable to an amount of analyte interacted with the at least one sensing element; and
a working electrode and a counter electrode;
wherein the working electrode is in proximity to the at least one sensing element; and
wherein the working electrode has a material upon the working electrode that is operable to generate or consume protons when applying a potential or current thereto.

### Claim 2 (depends on 1)

The affinity sensor of claim 1, wherein the recognition moiety is a bio-based moiety or a biomimetic moiety.

### Claim 3 (depends on 2)

The affinity sensor of claim 2, wherein the recognition moiety comprises at least one member selected from the group consisting of an antibody, a protein, a polypeptide, an aptamer, an affimer, a molecularly imprinted polymer, a glycopolymer, an oligonucleotide, and any combination thereof.

### Claim 4 (depends on 1)

The affinity sensor of claim 1, wherein the signal is detectable optically, electrochemically, thermally, gravimetrically, calorimetrically, or any combination thereof.

### Claim 5 (depends on 1)

The affinity sensor of claim 1, wherein the analyte and/or the recognition moiety undergoes protonation or deprotonation or a conformation change upon a pH change occurring in proximity to the at least one sensing element.

### Claim 6 (depends on 1)

The affinity sensor of claim 1, wherein the working electrode and the at least one sensing element are located upon an in-common substrate and wherein a separation between the working electrode and the at least one sensing element is 900 microns or less.

### Claim 7 (depends on 1)

The affinity sensor of claim 1, wherein the material comprises at least one member selected from the group consisting of a metal hydride, a metal oxide, and any combination thereof.

### Claim 8 (depends on 1)

The affinity sensor of claim 1, wherein the working electrode comprises a Pd/PdH working electrode.

### Claim 9

A method comprising:
providing an affinity sensor comprising:
at least one sensing element comprising a recognition moiety that interacts with an analyte by reversibly forming an analyte complex;
wherein formation of the analyte complex is pH-dependent; and
wherein the at least one sensing element provides a signal that changes when the analyte complex reversibly forms, and a change in magnitude of the signal is correlatable to an amount of analyte interacted with the at least one sensing element; and
a solid state pH modulating element in proximity to the at least one sensing element;
a working electrode and a counter electrode;
wherein the working electrode is in proximity to the at least one sensing element; and
wherein the working electrode has a material upon the working electrode that is operable to generate or consume protons when applying a potential or current thereto; and
interacting an analyte with the sensing element comprising a recognition moiety that reversibly forms an analyte complex in a pH-dependent manner, the sensing element changing from a first state to a second state upon interacting with the analyte to form the analyte complex;
wherein the sensing element provides a signal that changes when the analyte complex reversibly forms, and a change in magnitude of the signal between the first state and the second state is correlatable to an amount of analyte interacted with the sensing element; and
actuating the working electrode.

### Claim 10 (depends on 9)

The method of claim 9, wherein actuating the working electrode comprises applying a potential or current between the working electrode and the counter electrode.

### Claim 11 (depends on 10)

The method of claim 10, wherein actuating the working electrode changes pH at the sensing element and displaces the analyte from the analyte complex to convert the sensing element from the second state to the first state.

### Claim 12 (depends on 10)

The method of claim 10, wherein actuating the working electrode changes pH at the sensing element to allow that analyte complex to form when interacting the analyte with the sensing element.

### Claim 13 (depends on 10)

The method of claim 10, wherein the material upon the working electrode is selected from the group consisting of a metal hydride, a metal oxide, polyaniline, a quinone-containing polymer, and any combination thereof.

### Claim 14 (depends on 10)

The method of claim 10, wherein the working electrode is a Pd/PdH working electrode.

### Claim 15 (depends on 9)

The method of claim 9, wherein the recognition moiety is a bio-based moiety or a biomimetic moiety.

### Claim 16 (depends on 15)

The method of claim 15, wherein the recognition moiety comprises at least one member selected from the group consisting of an antibody, a protein, a polypeptide, an aptamer, an affimer, a molecularly imprinted polymer, a glycopolymer, an oligonucleotide, and any combination thereof.

### Claim 17 (depends on 9)

The method of claim 9, further comprising:
determining the change in magnitude of the signal; and
correlating the change in magnitude of the signal to the amount of analyte that is interacted with the sensing element.

### Claim 18 (depends on 9)

The method of claim 9, wherein the signal is detectable optically, electrochemically, thermally, gravimetrically, calorimetrically, or any combination thereof.

### Claim 19 (depends on 9)

The method of claim 9, wherein the working electrode and the sensing element are located upon an in-common substrate.

### Claim 20 (depends on 9)

The method of claim 9, further comprising:
adjusting pH in a sample containing the analyte before interacting the analyte with the sensing element.

### Claim 21 (depends on 9)

The method of claim 9, wherein the analyte and/or the recognition moiety undergoes protonation or deprotonation or a conformation change upon a pH change occurring in proximity to the at least one sensing element.
