Non-faradaic Nanopore Sequencing with AC Voltage Signals

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Solution Overview

Problem

Nanopore-based sequencing technologies face challenges with the operational lifespan of metal electrodes due to faradaic conduction, leading to electrode depletion and ion concentration imbalances, which affect the robustness and efficiency of DNA sequencing processes.

Innovation Solution

Implementing non-faradaic conduction through a nanopore-based sequencing chip with a platinum or gold electrode, utilizing AC signals to draw and release tagged nucleotides, thereby avoiding chemical reactions at the electrode surface and maintaining electrode integrity, and enhancing the double layer capacitance to improve current differentiation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If faradaic conduction is used in nanopore-based sequencing, then DNA sequencing can be performed, but electrode lifespan is reduced due to electrode depletion and chemical reactions at the electrode surface

Engineering Contradiction:
ImproveDNA sequencing throughputVSAvoidelectrode lifespan
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the electrical conduction mode from faradaic to non-faradaic by applying AC signals instead of DC voltages. This parameter change eliminates chemical reactions at the electrode surface while maintaining the ability to drive ion transport through the nanopore, thus preserving electrode integrity and extending electrode lifespan without sacrificing sequencing capability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs periodic AC voltage signals to drive ion transport through the nanopore. The alternating current periodically reverses direction, creating time-varying electric fields that maintain ion concentration gradients and drive molecular translocation without causing cumulative electrode depletion, thereby extending electrode operational life while maintaining sequencing throughput

Inventive Principle:
Principle #19Periodic action

2Productivity

If faradaic conduction is used to draw molecules through the nanopore, then sequencing can proceed, but ion concentration imbalances and osmotic pressure issues arise

Engineering Contradiction:
Improvesequencing efficiencyVSAvoidion concentration imbalance
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The AC signal periodically reverses the electric field direction, preventing the accumulation of ions at the electrode surfaces that occurs with DC-driven faradaic conduction. This periodic reversal maintains ion concentration balance in the electrolyte, eliminating osmotic pressure imbalances while preserving the ability to drive molecular translocation for efficient sequencing

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

By changing from DC to AC voltage application, the patent transforms the conduction mode to non-faradaic, which eliminates the harmful ion concentration imbalances and osmotic pressure issues associated with faradaic conduction, while maintaining sequencing efficiency through capacitive coupling effects

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If non-faradaic conduction with AC signals is used, then electrode lifespan is prolonged and ion concentration imbalances are reduced, but measurement accuracy must be maintained

Engineering Contradiction:
Improveelectrode lifespanVSAvoidcurrent measurement accuracy
Core Design Contradiction:
Duration of action of stationary objectVSMeasurement precision

Solution Approach 1:

The patent introduces a transimpedance amplifier as an intermediary device that converts the small capacitive currents generated during non-faradaic conduction into measurable voltage signals. This intermediary amplification stage enables accurate current measurement in the non-faradaic regime, preserving measurement precision while enjoying the benefits of extended electrode lifespan and reduced ion concentration imbalances

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent optimizes AC signal parameters (frequency, amplitude, duty cycle) to maximize the capacitive coupling effect while maintaining sufficient signal strength for accurate measurement. By carefully tuning these parameters, the system achieves both extended electrode life through non-faradaic conduction and maintained measurement accuracy through optimized signal characteristics

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 prolongs the lifespan of metal electrodes, reduces osmotic pressure imbalances, and enables efficient, high-throughput DNA sequencing by maintaining electrode integrity and improving current measurement accuracy.

Implementation Method 1

applying a first voltage signal to a pair of electrodes during a first period to draw a molecule to a nanopore

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

applying a second voltage signal to the pair of electrodes during a second period to release the molecule from the nanopore

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 3

Implementing non-faradaic conduction through a nanopore-based sequencing chip with a platinum or gold electrode, utilizing AC signals to draw and release tagged nucleotides, thereby avoiding chemical reactions at the electrode surface

Methodology Applied
Scientific EffectNon-faradaic conduction:

Implementation Method 4

enhancing the double layer capacitance to improve current differentiation

Methodology Applied
Scientific EffectCapacitance: Capacitance

Data Source

PatentEP3058102B1Non-faradaic, capacitively coupled measurement in a nanopore cell array
Publication Date: 2020.04.29 ROCHE SEQUENCING SOLUTIONS INC
  • EP3058102B1 patent drawingFigure 1
  • EP3058102B1 patent drawingFigure 2
  • EP3058102B1 patent drawingFigure 3

AI summary

A method of identifying a molecule is disclosed. A molecule is drawn to a nanopore by applying a first voltage signal to a pair of electrodes during a first period, wherein the first voltage signal causes a first ionic current through the nanopore that is indicative of a property of a portion of the molecule proximate to the nanopore. The molecule is released from the nanopore by applying a second voltage signal to the pair of electrodes during a second period, wherein the second voltage signal causes a second ionic current through the nanopore. The first period and the second period are determined based at least in part on a net ionic current through the nanopore comprising the first ionic current and the second ionic current.