Nanopore Sensor Local Electrical Potential Transduction

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Solution Overview

Problem

Conventional nanopore sensing techniques face challenges in measuring small ionic current signals at high bandwidth due to signal amplitude and bandwidth limitations, making it difficult to achieve effective DNA sequencing and molecular detection.

Innovation Solution

A nanopore sensor system employing a local electrical potential sensing method, which uses a transduction element to provide high sensitivity and bandwidth, enabling differentiation between objects translocating through the nanopore.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ionic current measurement method is used for nanopore sensing, then molecular translocation detection is enabled, but signal amplitude is too small and bandwidth is insufficient for fast molecular translocation

Engineering Contradiction:
Improvesignal amplitudeVSAvoidbandwidth
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent introduces an intermediary transduction element (such as a transistor or other electronic sensor) that converts the ionic current signal into an electrical potential signal. This intermediary device amplifies the signal and enables high-bandwidth measurement, resolving the contradiction between small signal amplitude and insufficient bandwidth.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the direct ionic current measurement approach with an electrical potential measurement approach using electronic sensors. This substitution allows for high-bandwidth signal acquisition while maintaining sensitivity to molecular translocation events.

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

2Measurement precision

If conventional ionic current detection is used, then nanopore translocation can be detected, but signal differentiation between different molecules is insufficient

Engineering Contradiction:
Improvesignal differentiationVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The transduction element serves as an intermediary that converts ionic current changes into electrical potential changes, providing enhanced signal differentiation. This intermediary device enables better discrimination between different molecules while maintaining a relatively simple measurement system architecture.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If parallel multiplexed format is used for recording current signals, then throughput is increased, but recording small current signals at high bandwidth becomes extremely difficult

Engineering Contradiction:
ImprovethroughputVSAvoidsignal detection difficulty
Core Design Contradiction:
ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces ionic current measurement with electrical potential measurement using electronic sensors in a parallel multiplexed format. This substitution enables easy recording of signals at high bandwidth while maintaining high throughput, as electronic sensors can efficiently handle multiple channels simultaneously.

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

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 allows for accurate DNA sequencing and molecular detection by enhancing signal differentiation and measurement sensitivity, overcoming the limitations of conventional methods.

Implementation Method 1

measurement of local electrical potential at the nanopores

Methodology Applied
Scientific EffectElectrical potential measurement: Electric Field

Data Source

PatentEP3825687B1Multi-nanopore sensor system and transduction elements for measurement of local electrical potential at the nanopores
Publication Date: 2024.06.05 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • EP3825687B1 patent drawingFigure 1A~1C
  • EP3825687B1 patent drawingFigure 1B
  • EP3825687B1 patent drawingFigure 1D

AI summary

There is provided a nanopore disposed in a support structure, with a fluidic connection between a first fluidic reservoir and an inlet to the nanopore and a second fluidic connection between a second fluidic reservoir and an outlet from the nanopore. A first ionic solution of a first buffer concentration is disposed in the first reservoir and a second ionic solution of a second buffer concentration, different than the first concentration, is disposed in the second reservoir, with the nanopore providing the sole path of fluidic communication between the first and second reservoirs. An electrical connection is disposed at a location in the nanopore sensor that develops an electrical signal indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore between the two reservoirs.