Electrochemical Sensor Nanoparticle Multiplexing

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Solution Overview

Problem

Current immunoassays, including ELISA and electrochemical sensor platforms, face challenges in detecting low concentrations of multiple analytes simultaneously due to high sample volume requirements, limited spatial resolution, and costly equipment, making it difficult to detect pathogens or endotoxins at sensitive levels effectively.

Innovation Solution

A method involving an electrochemical sensor with multiple analyte-specific electrodes functionalized with capture probes, where nanoparticles coated with capture probes are used to bind target analytes, followed by labeling with reporter enzyme-conjugated label probes and application of an electroactive mediator to detect target analytes through voltage application, allowing for simultaneous detection of multiple analytes in a single sample.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If electrochemical sensor platforms are used for detection, then sensitivity is improved, but device complexity and cost increase due to photolithographic microfabrication requirements

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

Solution Approach 1:

The patent employs disposable screen-printed electrode arrays that can be mass-produced using inexpensive printing techniques rather than expensive photolithography. These single-use electrodes eliminate the need for complex clean room fabrication while maintaining adequate detection sensitivity for the application.

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

Solution Approach 2:

The patent replaces the photolithographic mechanical fabrication system with a chemical/electrochemical approach using screen-printing technology. This substitution dramatically simplifies the manufacturing process while achieving the necessary electrode functionality for multiplexed detection.

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

2Measurement precision

If multiple analytes are detected in separate wells, then measurement precision is maintained, but sample volume requirements increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent combines multiple analyte detection capabilities into a single well by implementing an electrode array where each electrode is functionalized with different capture probes. This merging allows simultaneous multiplexed detection of multiple analytes in one sample volume, eliminating the need for separate wells for each analyte.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The electrode array serves multiple functions within a single well: each electrode acts as an independent detection channel for different analytes, while the shared well provides a common reaction environment. This multi-functionality reduces sample volume requirements while maintaining detection precision.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If electroactive mediator is applied to enhance signal, then measurement precision improves, but chemical cross-talk between electrodes increases

Engineering Contradiction:
Improvesignal strengthVSAvoidchemical cross-talk
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by functionalizing each electrode with specific capture probes that bind only to their target analytes. This spatial differentiation ensures that electroactive mediators generate signals locally at each electrode-site interface, preventing cross-talk between adjacent electrodes while maintaining strong signals.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses analyte-specific capture probes as intermediaries between the electroactive mediator and the detection system. These probes ensure that the mediator's signal generation is localized to specific electrode-analyte complexes, preventing harmful chemical cross-talk while enhancing measurement precision.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of operation

If conventional immunoassays are used, then ease of operation is maintained, but detection sensitivity for low concentrations deteriorates

Engineering Contradiction:
Improveassay simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent replaces conventional colorimetric readout methods with electrochemical detection, substituting complex optical instrumentation with simpler electrochemical measurement systems. This substitution maintains ease of operation while dramatically improving detection sensitivity for low analyte concentrations.

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

Solution Approach 2:

The patent changes the detection parameter from optical (colorimetric) to electrochemical, allowing detection of much lower analyte concentrations. This parameter change enables sensitive detection of low concentrations while maintaining operational simplicity through automated electrochemical measurement.

Inventive Principle:
Principle #35Parameter changes

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 enables sensitive and multiplexed detection of target analytes, reducing sample volume requirements and costs, while minimizing chemical cross-talk between electrodes, thereby improving the detection of low concentrations of pathogens and endotoxins.

Implementation Method 1

nanoparticles coated with capture probes are used to bind target analytes

Methodology Applied
Scientific EffectSpecific binding: Absorption (physical)

Implementation Method 2

labeling with reporter enzyme-conjugated label probes and application of an electroactive mediator

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

applying a voltage to the electrochemical sensor, wherein the voltage corresponds to the standard redox potential of the electroactive precipitate; and measuring a current generated from the analyte-specific electrode

Methodology Applied
Scientific EffectElectrochemical detection: Redox Reactions

Data Source

PatentUS20200378978A1Enhanced electrochemical detection using nanoparticles and precipitation
Publication Date: 2020.12.03 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US20200378978A1 patent drawing
  • US20200378978A1 patent drawing
  • US20200378978A1 patent drawing

AI summary

The invention described herein relates generally to methods, sensors, devices and kits for electrochemical detection of a target analyte in a sample. In certain aspects, the methods, sensors, devices and kits described herein can be used to detect low concentrations of at least one target analyte using small sample volumes. In some embodiments, methods, sensors and kits for detecting a microbe, microbe fragment or released endotoxin in a test sample, including bodily fluids such as blood and tissues of a subject, food, water, and environmental surfaces, are also provided herein.