# US 10,481,154 B2 · Biomarker detection and self-separation of serum during capillary flow

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- Number: US 10,481,154 B2
- Document ID: US10481154B2
- Status: Granted
- Kind: B2
- Application number: 15/811,186
- Filed: 2017-11-13
- Published: 2018-05-10
- Granted: 2019-11-19
- Earliest claimed: 2016-11-10
- Assignees: New Jersey Institute of Technology
- Applicants: New Jersey Institute of Technology
- Inventors: Eon Soo Lee; Bharath Babu Nunna
- Web page: https://patentgrep.com/patent/US10481154B2

## CPC

- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- G01N 27/226: {Construction of measuring vessels; Electrodes therefor}
- G01N 27/227: {Sensors changing capacitance upon adsorption or absorption of fluid components, e.g. electrolyte-insulator-semiconductor sensors, MOS capacitors (G01N27/225 takes precedence)}
- G01N 33/5438: {Electrodes}
- G01N 33/545: Synthetic resin
- G01N 33/575: for cancer
- B01L 3/502746: {characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves}
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2200/143: Quality control, feedback systems
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0645: Electrodes
- B01L 2300/0819: Microarrays; Biochips
- B01L 2300/0896: Nanoscaled
- B01L 2300/16: Surface properties and coatings
- B01L 2400/0406: capillary forces
- B01L 2400/0409: centrifugal forces
- G01N 2600/00: Assays involving molecular imprinted polymers/polymers created around a molecular template
- 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

Molecularly Imprinted Polymers (MIPs) are utilized to detect diseases and minimize false negative/positive scenarios. MIPs are implemented on a nano-electric circuit in a biochip where interactions of MIPs and an Antigen/Antibody (AG/AB) are detected, and disease specific biomarkers diagnosed. Biomarker detection is achieved with interdigitated gold electrodes in a biochip's microchannel. Capacitance changes due to biomarker interaction with AG/AB electrode coating diagnose diseases in a microfluidic environment. Biofluid passes through the microchannel and exposed to the nanocircuit to generate a capacitance difference and diagnose any specific disease in the biofluid sample. Blood capillary flow in a microchannel curved section experience centrifugal forces that separate liquid from solid. Various blood densities and segments experience different centrifugal effects while flowing through the curved section so serum is separated from various solid matter without using external devices.

## Claims

### Claim 1

A method of using a biomarker detection and serum self-separation device, comprising:
providing a single micro biochip having a molecular imprinted polymer (MIP) that is used as an artificial antibody to sense an antigen/antibody (AG/AB) interaction, wherein the MIP is disposed unto an interdigitated electrode that is part of a nano circuit on the biochip, and the biochip is a self-evaluation device that functions by itself without any aid of external devices;
placing a biofluid sample containing an antigen on the biochip;
detecting the AG/AB interaction of a biomarker with the MIP using an electrical signal output with a hybrid method utilizing at least a variation of capacitance charge;
diagnosing a disease in the biofluid sample; and
determining a severity of the disease is sensed depending on intensity of the signal output.

### Claim 2 (depends on 1)

The method of claim 1, wherein the electrode contains gold (Au).

### Claim 3 (depends on 1)

The method of claim 1, wherein the electrical signal is a change in capacitance in the nano circuit.

### Claim 4 (depends on 1)

The method of claim 1, wherein the diagnosing is for a complex disease including cancer.

### Claim 5 (depends on 1)

The method of claim 1, wherein the MIP is fabricated with a desired sensitivity and specificity for a specific disease.

### Claim 6 (depends on 5)

The method of claim 5, wherein the sensitivity and specificity of the MIP decreases false negative and false positive diagnosis scenarios.

### Claim 7 (depends on 1)

The method of claim 1, wherein the MIP is sub-layered with various biomolecules in order to diagnosis various diseases.

### Claim 8 (depends on 1)

The method of claim 1, wherein the interdigitated electrode is placed in a specific shaped microchannel of the biochip.

### Claim 9 (depends on 1)

The method of claim 1, further including diagnosing a disease biomarker using the nanocircuit in a microfluidic environment.

### Claim 10 (depends on 1)

The method of claim 1, wherein the interdigitated electrode has a plurality of fingers that are patterned and made of different conducting materials.

### Claim 11 (depends on 1)

The method of claim 1, wherein the interdigitated electrodes dimensions are directly related to capacitance generation.

### Claim 12 (depends on 1)

The method of claim 1, wherein the interdigitated electrodes further includes intermediate layers between the electrodes and an AG/AB complex formed by the AG/AB interaction of the antigen and the artificial antibody, and the intermediate layers are a coating to enhance the sensing ability.

### Claim 13 (depends on 12)

The method of claim 12, wherein the intermediate layers are selected from a group consisting of a conductive metal, gold (AU) nano particles, bovine serum albumin (BSA), a biomaterial, and any combination thereof.

### Claim 14 (depends on 1)

The method of claim 1, wherein the hybrid method further includes Temperature Variation, and Variation Electric Oscillation to detect and diagnose both the disease and the severity of the disease.

### Claim 15 (depends on 1)

The method of claim 1, wherein the biofluid sample is directly applied on the biochip without any sample preparation requirement, and the nano circuit generates necessary forces and electrical charges required for the functionality of the biochip without any aid of external devices.

### Claim 16 (depends on 1)

The method of claim 1, wherein the biofluid is separated in a microchannel of the biochip without bifurcating the microchannel so that the biofluid is separated into liquid and solid matters with use of only the microchannel.

### Claim 17 (depends on 1)

The method of claim 1, wherein the biochip further includes a microchannel having a natural antibody, and the antigen from the biofluid forms an antigen-antibody (AG/AB) complex.

### Claim 18 (depends on 17)

The method of claim 17, further includes a sensor mechanism on the biochip to detect the AG/AB interaction from both the natural antibody and the artificial antibody of the MIP.