Nanopore Multi-Electrode Detection for DNA Sequencing Noise

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Solution Overview

Problem

Current nanopore devices for molecular detection face challenges in achieving high accuracy due to high noise levels, sensitivity to analyte orientation, and limited signal transduction mechanisms, particularly in DNA sequencing applications, where ionic current signals are prone to noise and variability, affecting the reliability of nucleotide identification.

Innovation Solution

A method that simultaneously measures double layer potential, ionic current, and mobility signals from a single molecule, allowing for multi-channel detection and analysis, which enhances the characterization of analytes by considering probability distributions in Hidden Markov Models to improve error rates and reduce noise sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ionic current measurement is used for signal transduction in nanopores, then molecular detection can be achieved, but noise levels are high and measurement precision deteriorates

Engineering Contradiction:

Improvesignal transduction reliabilityVSAvoidnucleotide identification accuracy

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent transitions from one-dimensional ionic current measurement to two-dimensional electrical field mapping by measuring potential differences at multiple locations around the nanopore. This dimensional expansion allows spatial resolution of charge distributions, enabling accurate nucleotide identification while filtering out noise through spatial pattern recognition rather than relying on noisy current amplitude alone.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent divides the continuous ionic current signal into discrete spatial components by placing multiple electrodes around the nanopore. Each electrode measures the electrical field contribution from specific regions, segmenting the overall signal into spatially-resolved components that can be individually analyzed and combined to improve measurement precision and reduce noise.

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If transverse conductance measurements are used to overcome noise, then signal quality improves, but sensitivity to analyte orientation increases which limits usefulness

Engineering Contradiction:

Improvesignal qualityVSAvoidanalyte orientation sensitivity

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal detection system where multiple electrodes arranged around the nanopore can detect analytes regardless of their orientation. By measuring electrical field patterns from multiple angular positions, the system can identify nucleotides in any orientation, making the detection method versatile and independent of analyte alignment, thus overcoming the limitation of orientation-sensitive transverse conductance measurements.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Ease of manufacture

If solid-state nanopores are used instead of biological nanopores, then customization and fabrication ease improve, but signal transduction mechanisms remain limited

Engineering Contradiction:

Improvenanopore fabricationVSAvoidsignal transduction mechanisms

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent combines solid-state nanopore materials (such as silicon nitride or silicon oxide) with multiple metallic electrodes to create a composite sensing system. The solid-state nanopore provides fabrication advantages and stability, while the integrated multi-electrode structure enables sophisticated electrical field mapping and potential difference measurements, thereby expanding signal transduction capabilities beyond what single-material systems can achieve.

Inventive Principle:

Principle #40Composite materials

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 improved accuracy in DNA sequencing and analyte identification by combining multiple signals, reducing noise and orientation sensitivity, and enabling the detection of analytes in mixtures without chemical tagging, with a reusable solid-state nanopore device requiring minimal reagents and exhibiting long operational life.

Implementation Method 1

measure the charging potential of the electrical double layer capacitance within a nanopore

Methodology Applied

Scientific EffectElectrical double layer capacitance: Capacitance

Implementation Method 2

measure the ionic current through the nanopore

Methodology Applied

Scientific EffectIonic current: Conduction (electrical)

Implementation Method 3

measure the analyte mobility

Methodology Applied

Scientific EffectElectrophoretic mobility: Electrophoresis

Data Source

PatentUS10883962B2Electrical double layer in nanopores for detection and identification of molecules and submolecular units

Publication Date: 2021.01.05 UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION

AI summary

Systems for detecting analytes in electrical double layer nanopore devices and methods of use are provided.