Biosensor System for Biomarker Detection via Impedance Spectroscopy

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Solution Overview

Problem

Current methods for detecting biomarkers, such as ELISA, flow cytometry, and electrochemiluminescence, face challenges including laboriousness, high costs, false negatives and positives, and limitations in sensitivity and specificity, particularly in detecting COVID-19 antigens and differentiating between active and remitted infections.

Innovation Solution

A biosensor system utilizing a glutaraldehyde-functionalized carbon nanoparticle paste with immobilized antibodies and optional blocking agents, applying alternating voltage to measure electrical impedance spectroscopy (EIS) signals for detecting biomarkers, including COVID-19-specific antigens, in various biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ELISA method is used for biomarker detection, then high specificity and sensitivity are achieved, but the method becomes laborious and expensive

Engineering Contradiction:
Improvedetection sensitivityVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical/chemical ELISA detection system with an electrochemical impedance spectroscopy system. The biosensor uses electrochemical reactions and impedance measurements to detect biomarkers, substituting the traditional enzyme-linked immunosorbent assay mechanism with an electrical measurement approach that is faster and less labor-intensive while maintaining detection sensitivity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from optical/chemical readout in ELISA to electrical impedance measurement. By measuring impedance changes caused by biomarker binding events, the system achieves high sensitivity without requiring the complex multi-step ELISA protocol, thereby reducing assay complexity and labor requirements

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If antibodies are used in ELISA, then high detection specificity is achieved, but cost increases due to antibody instability and storage requirements

Engineering Contradiction:
Improvedetection specificityVSAvoidreagent cost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent substitutes traditional antibodies with molecularly imprinted polymers (MIPs) or other stable recognition elements on the biosensor surface. These alternatives provide comparable detection specificity without the instability and storage requirements of protein-based antibodies, thereby reducing reagent costs and eliminating refrigeration needs

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs disposable biosensor devices with integrated recognition elements that do not require long-term storage. The biosensors can be manufactured at low cost and used immediately, eliminating the need for expensive, temperature-sensitive antibody reagents and their associated storage infrastructure

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Adaptability or versatility

If flow cytometry is used for biomarker detection, then multiparameter analysis is achieved, but cell structural information is lost

Engineering Contradiction:
Improveanalysis capabilityVSAvoidstructural information
Core Design Contradiction:
Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent uses a biosensor surface as an intermediary that captures biomarkers while preserving their spatial and structural context. The immobilized recognition elements on the sensor surface allow binding events to occur in a controlled environment that maintains structural information, unlike flow cytometry where cells are suspended and structurally disrupted

Inventive Principle:
Principle #24Intermediary (Mediator)

4Measurement precision

If electrochemiluminescence method is used, then sensitivity is improved, but electrode encrustation occurs frequently

Engineering Contradiction:
Improvedetection sensitivityVSAvoidelectrode stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces the electrochemiluminescence detection system with electrochemical impedance spectroscopy. This substitution eliminates the luminol reagent and associated electrode encrustation problems while maintaining high detection sensitivity through impedance measurements that are not susceptible to electrode fouling

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs disposable biosensor electrodes that eliminate the reliability issues of reusable electrodes subject to encrustation. Each biosensor is designed for single use, ensuring consistent performance without the degradation and fouling problems that affect reusable electrochemiluminescence electrodes

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides rapid and sensitive detection of biomarkers, distinguishing between active and remitted COVID-19 infections, and offers a cost-effective solution with improved specificity and sensitivity compared to existing methods.

Implementation Method 1

a modified biosensor, the biosensor comprising: (i) a glutaraldehyde-functionalized carbon nanoparticle paste; (ii) one or more immobilized antibodies specific to the biomarker

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

applying an alternating voltage to the modified biosensor; (d) measuring an electrical impedance spectroscopy (EIS) signal to determine the presence of the biomarker

Methodology Applied
Scientific EffectElectrical impedance: Electrical Resistance

Implementation Method 3

applying an alternating voltage to the modified biosensor; measuring an electrical impedance spectroscopy (EIS) signal

Methodology Applied
Scientific EffectElectrochemical reaction: Electrolysis

Data Source

PatentUS20240027452A1Methods, devices and systems for detection of biomarkers
Publication Date: 2024.01.25 NOOR BRANDS CO LLC
  • US20240027452A1 patent drawing
  • US20240027452A1 patent drawing
  • US20240027452A1 patent drawing

AI summary

Disclosed are methods, systems and devices for detection of biomarkers. In certain embodiments, the methods and/or devices and/or systems may be used for the detection of biomarkers characteristic of disease. For example, disclosed are methods, systems and devices that may be used to detect and distinguish a biomarker profile indicative of the presence of COVID-19 as either an active infection, or a subject in remission, or a subject who has not been exposed to the virus.