Nanopore Sequencing Circuit Using AC Readout to Eliminate RC Transients

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Solution Overview

Problem

State-of-the-art nanopore sequencing technologies face challenges with scalability, requiring large amplifiers due to small currents and suffer from RC transients, making direct current readouts inaccurate and difficult.

Innovation Solution

Implementing an alternating current (AC) input system with field effect transistors (FETs) to measure AC responses, allowing for faster and more accurate sequencing by modulating ionic fluxes through nanopores, and using non-Faradaic conduction to eliminate RC transients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If direct current (DC) readout is used for nanopore sequencing, then the ionic current can be measured, but RC transients occur making the measurement inaccurate and requiring waiting time for steady state

Engineering Contradiction:

Improveionic current measurement accuracyVSAvoidwaiting time for steady state

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies periodic action by using alternating current (AC) instead of direct current (DC) for readout. The AC signal periodically modulates the ionic current through the nanopore, allowing measurements to be taken during the AC cycle rather than waiting for DC steady state. This periodic modulation enables accurate current measurement while eliminating the time delay associated with RC transient decay in DC systems.

Inventive Principle:

Principle #19Periodic action

2Volume of moving object

If small trans-well volumes are used for sequencing, then the device size is reduced, but the ionic current becomes too small requiring large amplifiers

Engineering Contradiction:

Improvetrans-well volumeVSAvoidamplifier size

Core Design Contradiction:

Volume of moving objectVSDevice complexity

Solution Approach 1:

The patent substitutes the mechanical/electronic amplifier system with an AC-based measurement approach. Instead of using large amplifiers to detect small DC currents from small trans-well volumes, the system uses AC modulation to generate measurable current signals directly proportional to the ionic flux, eliminating the need for bulky amplification hardware while maintaining sensitivity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If bilayer capacitance is large in nanopore systems, then the membrane can effectively separate compartments, but switching readout becomes difficult and RC transients are prolonged

Engineering Contradiction:

Improvemembrane compartment separationVSAvoidreadout switching capability

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent uses periodic AC action to overcome the limitations of large bilayer capacitance. The AC signal enables dynamic modulation of the ionic current despite the capacitive properties of the bilayer membrane, allowing for effective readout switching without being constrained by the RC time constant. The periodic nature of AC allows the system to operate effectively with the inherent capacitance of the membrane.

Inventive Principle:

Principle #19Periodic 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

Enables scalable, high-bandwidth, and accurate nanopore sequencing without buffer consumption, allowing for simultaneous detection of multiple biopolymers, and reducing the need for amplifiers.

Implementation Method 1

an electrical source configured to provide alternating current (AC) inputs between the one or more cis electrodes and the source terminals of the plurality of FETs

Methodology Applied

Scientific EffectAlternating current (AC):

Implementation Method 2

measuring the ionic current of prior nanopores

Methodology Applied

Scientific EffectIonic conduction: Conduction (electrical)

Implementation Method 3

a plurality of field effect transistors (FETs), each of the plurality of FETs associated with one of the plurality of trans wells

Methodology Applied

Scientific EffectField effect transistor (FET):

Implementation Method 4

using non-Faradaic conduction to eliminate RC transients

Methodology Applied

Scientific EffectNon-Faradaic conduction:

Implementation Method 5

nanopore, which can provide a path for an ionic electrical current

Methodology Applied

Scientific EffectNanopore conduction: Conduction (electrical)

Implementation Method 6

as the polynucleotide traverses through the nanopore, it influences the electrical current through the nanopore

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS12493024B2Scalable circuit for molecular detection

Publication Date: 2025.12.09 ILLUMINA INC

AI summary

In one aspect, the disclosed technology relates to systems and methods for sequencing polynucleotides. In one embodiment, the disclosed technology relates to a nanopore sensor device for identifying nucleotides, the nanopore sensor device including: one or more cis wells; one or more cis electrodes associated with the one or more cis wells; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid or solid-state membrane having a nanopore; a plurality of field effect transistors (FETs), each of the plurality of FETs associated with one of the plurality of trans wells; an electrical source configured to provide alternating current (AC) inputs between the one or more cis electrodes and the source terminals of the plurality of FETs; and a controller operably coupled to the plurality of FETs, the controller configured to measure AC responses of the plurality of FETs, wherein the AC responses depend on the identities of the nucleotides within or near the nanopores.