Biosensor Electrode Activation for Protein Detection

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Solution Overview

Problem

Current methods for detecting biological entities in biofluids, such as those indicative of cancer, are often invasive, time-consuming, and require large reagent consumption, making them unsuitable for point-of-care diagnostics and environmentally inefficient.

Innovation Solution

A method using a sensor with a substrate and electrodes, where metallic nanoparticles are treated with an activation voltage to fuse with target biological entities, increasing the current detected by several orders of magnitude, allowing for sensitive and efficient detection in a non-invasive manner.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If amplification and sequencing technologies are used to detect nucleic acids, then detection accuracy is improved, but reagent consumption increases and the method becomes unsuitable for point-of-care integration

Engineering Contradiction:
Improvedetection accuracyVSAvoidreagent consumption
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and detects specific protein mediators (biomarkers) directly from biofluids using targeted immunoassays, rather than performing comprehensive nucleic acid amplification and sequencing. This extraction approach focuses resources on detecting only the relevant cancer-associated proteins, significantly reducing reagent consumption while maintaining detection accuracy for the specific biomarkers of interest.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs localized detection of specific protein mediators at targeted sites within the biofluid sample, using spatially resolved analysis to identify cancer-related proteins. This local quality approach allows for precise detection of biomarkers without the need for whole-genome amplification, reducing reagent requirements while maintaining measurement precision for the specific proteins being detected.

Inventive Principle:
Principle #3Local quality

2Reliability

If invasive procedures such as tissue biopsy are used, then reliability of detection is improved, but patient convenience deteriorates and the procedure becomes time-consuming

Engineering Contradiction:
Improvereliability of detectionVSAvoidpatient convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses protein mediators (biomarkers) present in biofluids as intermediary indicators of cancer presence and status. These protein mediators serve as surrogates that can be detected non-invasively from blood or other body fluids, providing reliable cancer detection information without requiring direct tissue sampling. The mediators carry the diagnostic information from the tumor site to the accessible biofluid compartment.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If comprehensive nucleic acid sequencing is performed, then complete cancer profiling is achieved, but the method becomes time-consuming and leaves significant environmental footprints

Engineering Contradiction:
Improvecompleteness of cancer profileVSAvoiddetection time
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The patent extracts and detects only the specific protein mediators relevant to cancer diagnosis and monitoring from the complex biofluid sample, rather than performing comprehensive nucleic acid sequencing. This targeted extraction approach identifies the essential cancer-related information carried by specific proteins, providing complete cancer profiling for the markers of interest without the time-consuming whole-genome analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs partial action by detecting a selected panel of protein mediators that are most relevant to cancer detection and monitoring, rather than attempting to analyze all possible nucleic acid sequences. This partial action approach captures the critical diagnostic information needed for cancer profiling while significantly reducing the time and resources required compared to comprehensive sequencing.

Inventive Principle:
Principle #16Partial or excessive action

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 simplifies the detection of target biological entities by enhancing the electrical connection between nanoparticles and electrodes, enabling quick and sensitive detection of proteins in biofluids, suitable for point-of-care diagnostics with reduced environmental impact.

Implementation Method 1

Biofunctionalized gold nanoparticles in the gap region are subjected to repeated I-V scans at a voltage range of -5 to 5 V to produce a stable I-V curve

Methodology Applied
Scientific EffectElectrical conduction enhancement: Conduction (electrical)

Implementation Method 2

The conditioning comprises applying an activation voltage between the electrodes to increase a degree of connection between a surface of the pair of electrodes and at least one nanoparticle in contact with the surface

Methodology Applied
Scientific EffectJoule heating: Joule Heating

Data Source

PatentEP4052038B1Biosensor activation and conditioning method
Publication Date: 2024.08.28 MURSLA LTD
  • EP4052038B1 patent drawingFigure 1
  • EP4052038B1 patent drawingFigure 2
  • EP4052038B1 patent drawingFigure 3a~4b

AI summary

A method of detecting a target biological entity in a biofluid using a sensor, wherein the biofluid comprises a plurality of the target biological entities and nanoparticles, the sensor comprising a substrate bearing a pair of electrodes having an affinity with the nanoparticles, and wherein a region between the electrodes defines a sensing region. The method comprises: treating the biofluid with a suspension comprising a plurality of nanoparticles to obtain a treated mixture comprising bound nanoparticle-entity assemblies; introducing the treated mixture to the sensor; conditioning the sensor in the presence of the treated mixture by applying an activation voltage between the electrodes to increase a degree of connection between a surface of the pair of electrodes and at least one bound nanoparticle-entity assembly in contact with the surface of the pair of electrodes; and detecting the presence of target biological entities by using the pair of electrodes to detect a current through the at least one bound nanoparticle-entity assembly.