Trapped Charge Nanopore Insertion Control

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Nanopore-based sequencing chips face challenges in reliably inserting a single pore into the membrane without excessively damaging it, making it difficult to interpret electrical signatures from multiple pores and reducing the stability of the membrane.

Innovation Solution

A method involving flowing a solution with a membrane-forming material and an organic solvent over a sequencing chip, applying a voltage to trap charge, and then displacing the solution to form a membrane capable of receiving a nanopore, with controlled voltage waveforms to facilitate single pore insertion and prevent membrane damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If voltage is applied across the membrane to facilitate pore insertion, then pore insertion is improved, but membrane damage increases

Engineering Contradiction:

Improvepore insertion reliabilityVSAvoidmembrane damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies voltage in a controlled, stepwise manner before pore insertion to pre-condition the membrane and reduce insertion barriers. By applying preliminary voltage to thin the membrane and prepare it for pore formation, the system achieves reliable pore insertion while avoiding the need for excessive voltage that would cause membrane damage.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs dynamic voltage control where the voltage applied across the membrane is continuously adjusted based on membrane thickness and pore insertion progress. The system transitions from higher voltage during membrane thinning to lower voltage during pore insertion, optimizing the balance between facilitating pore formation and preventing membrane damage throughout the process.

Inventive Principle:

Principle #15Dynamics

2Quantity of substance

If multiple pores are inserted into a single membrane, then pore capacity is improved, but electrical signature interpretability deteriorates

Engineering Contradiction:

Improvepore quantityVSAvoidelectrical signature interpretability

Core Design Contradiction:

Quantity of substanceVSLoss of information

Solution Approach 1:

The patent implements spatial control mechanisms that ensure only one pore is inserted into each individual membrane at a specific location. By controlling pore insertion at the local level (per membrane) rather than allowing random multiple insertions, the system maintains electrical signature interpretability while achieving high overall pore density across the array through localized precision control.

Inventive Principle:

Principle #3Local quality

3Manufacturing precision

If voltage is increased to ensure single pore insertion, then pore insertion control is improved, but membrane stability deteriorates

Engineering Contradiction:

Improvesingle pore insertion controlVSAvoidmembrane stability

Core Design Contradiction:

Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent incorporates feedback mechanisms that monitor membrane conditions during the pore insertion process. By detecting membrane thickness, voltage distribution, and insertion progress in real-time, the system adjusts the applied voltage to maintain optimal conditions for single pore insertion while preventing voltage levels that would compromise membrane stability. This closed-loop control ensures precision without sacrificing membrane integrity.

Inventive Principle:

Principle #23Feedback

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 ensures reliable single pore insertion into the membrane, reducing the risk of membrane damage and improving the interpretability of electrical signatures from nucleotides passing through the nanopore, enhancing the sequencing process.

Implementation Method 1

applying a first voltage between the working electrode and the counter electrode during the step of flowing the solution comprising the membrane forming material in order to trap a charge in the first aqueous solution in the well

Methodology Applied

Scientific EffectElectrostatic charge trapping: Electrostatics

Implementation Method 2

Application of voltage across the membrane during the pore insertion step may facilitate the process of pore insertion, possibly by reducing the stability of the membrane

Methodology Applied

Scientific EffectVoltage-induced membrane destabilization: Electric Field

Data Source

PatentUS20230087757A1Systems and methods for using trapped charge for bilayer formation and PORE insertion in a nanopore array

Publication Date: 2023.03.23 ROCHE SEQUENCING SOLUTIONS INC

AI summary

A nanopore-based sequencing chip can have a surface with an array of wells, with each well having a working electrode. Charge can be established within the wells by applying a voltage between the working electrodes and a counter electrode. The charge can then be trapped within the wells by sealing the wells with a membrane. The trapped charge can be used to facilitate pore insertion into the membranes.