# US 11,079,377 B2 · Nanopore coating for sensing chemical bond formation

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- Number: US 11,079,377 B2
- Document ID: US11079377B2
- Status: Granted
- Kind: B2
- Application number: 16/111,258
- Filed: 2018-08-24
- Published: 2020-02-27
- Granted: 2021-08-03
- Earliest claimed: 2018-08-24
- Assignees: International Business Machines Corporation
- Applicants: International Business Machines Corporation
- Inventors: Priscilla Racquel Rogers; Stefan Harrer; Ali Afzali-Ardakani; Jose Miguel Lobez Comeras; Sung Cheol Kim; Natalie J. Gunn
- Web page: https://patentgrep.com/patent/US11079377B2

## CPC

- G01N 33/5438: {Electrodes}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- G01N 27/3278: {involving nanosized elements, e.g. nanogaps or nanoparticles (nanopores G01N33/48721; magnetic beads G01N27/745)}
- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2300/0645: Electrodes
- B01L 2300/123: Flexible; Elastomeric
- B01L 2300/16: Surface properties and coatings
- B01L 2300/161: Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A process for monitoring binding events, a coating compound, and a device for monitoring binding events are disclosed. The process includes providing two reservoirs that contain an electrically conductive fluid, wherein the reservoirs are separated by a membrane having a nanopore. The process also includes selecting a target compound, selecting a ligand based on the selection of the target compound, and preparing a coating that includes the coating compound, wherein the coating compound includes the ligand and a moiety that immobilizes the ligand. Additionally, the process includes applying the coating to the inner surface of the nanopore, adding the target compound to a conductive liquid in the first chamber, establishing a voltage gradient across the membrane, and electrically monitoring translocation of the target molecule. The device includes the reservoirs and the membrane having the coated nanopore.

## Claims

### Claim 1

A process of monitoring binding events, comprising:
providing a first reservoir and a second reservoir, wherein the first reservoir and the second reservoir contain an electrically conductive fluid, and wherein the first reservoir and the second reservoir are separated by a membrane that includes a nanopore having an inner surface;
selecting a target compound;
preparing a biotin derivative having hydroxamic acid moiety;
preparing a solution of the biotin derivative;
adding the solution to the first reservoir;
establishing a voltage gradient across the membrane;
electrically monitoring formation of a coating on the inner surface of the nanopore, wherein the coating comprises molecules of the biotin derivative immobilized by adherence of the hydroxamic acid moiety to the inner surface;
rinsing the membrane with a solvent to remove excess molecules of the biotin derivative;
adding a solution of the target compound in a conductive liquid to the first chamber;
establishing a voltage gradient across the membrane; and
electrically monitoring translocation of the target molecule.

### Claim 2 (depends on 1)

The process of claim 1, wherein the biotin derivative is selected from a group of potential ligands identified by computational structure-based screening.

### Claim 3 (depends on 1)

The process of claim 1, wherein the electrically monitoring translocation comprises monitoring changes in ionic current in the electrically conductive fluid.

### Claim 4

A device for monitoring binding events, comprising:
two reservoirs containing an electrically conductive fluid;
a membrane separating the two reservoirs, wherein the membrane includes a nanopore having an inner surface extending through the membrane; and
a coating disposed on the inner surface of the nanopore, wherein the coating includes a self-assembled layer of biotin derivative molecules having hydroxamic acid moieties bound to the inner surface of the nanopore, and wherein the biotin derivative molecules are selected based on a selection of a target molecule.

### Claim 5 (depends on 4)

The device of claim 4, further comprising an electronic component.

### Claim 6 (depends on 5)

The device of claim 5, wherein the electronic component includes at least one complementary metal-oxide-semiconductor circuit.

### Claim 7 (depends on 4)

The device of claim 4, further comprising two electrodes.

### Claim 8 (depends on 7)

The device of claim 7, wherein the two electrodes are silver-silver chloride electrodes.

### Claim 9 (depends on 4)

The device of claim 4, wherein the diameter of the nanopore is in a range of approximately 10 nm 50 nm.

### Claim 10 (depends on 4)

The device of claim 4, wherein the length of the nanopore is in a range of approximately 20 μm-75 μm.

### Claim 11 (depends on 4)

The device of claim 4, wherein the two reservoirs and the membrane are integrated into a microfluidic chip.

### Claim 12 (depends on 4)

The device of claim 4, wherein the membrane is a silicon nitride membrane.