Nanopore Sequencer Membrane Isolation for Redox Mediator Stability

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Solution Overview

Problem

Nanopore sequencing devices suffer from low lifetimes due to interference from redox mediator species that can destabilize sequencing biochemistry and membranes, particularly when using polarizable and non-Faradaic electrode materials.

Innovation Solution

The nanopore sensing system incorporates a mechanism to physically separate the redox mediator species from the cis well and membrane using ion exchange membranes, size selective membranes, or redox active polymer coatings, preventing interference with sequencing biochemistry and maintaining membrane stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If redox mediator species are used with polarizable and non-Faradaic electrode materials, then sufficient current can be carried to the electrodes, but the redox mediator species interfere with sequencing biochemistry and destabilize membranes, reducing device lifetime

Engineering Contradiction:
Improvecurrent carrying capacityVSAvoiddevice lifetime
Core Design Contradiction:
Use of energy by moving objectVSReliability

Solution Approach 1:

The system is divided into separate compartments: a first compartment containing the redox mediator species and cis electrode, and a second compartment containing the sequencing biochemistry and membrane. The membrane physically separates these compartments, allowing independent optimization of each region without mutual interference, thus maintaining current carrying capacity while protecting the sequencing biochemistry and membrane from destabilization

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A redox-active polymer coating is applied to the cis electrode surface, serving as an intermediary layer. This coating enables electron transfer between the redox mediator species in the first compartment and the electrode while preventing direct contact between the redox mediator species and the sequencing biochemistry in the second compartment, thus maintaining electrical function while protecting sensitive components

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If redox mediator species are confined to a separate compartment, then interference with sequencing biochemistry and membrane stability is prevented, but device complexity increases

Engineering Contradiction:
Improvemembrane stabilityVSAvoidsystem structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The membrane serves multiple functions simultaneously: it acts as a physical barrier to separate compartments, provides structural support for the nanopore, and enables ion transport between compartments. By combining these functions into a single component, the system achieves reliable membrane stability without proportionally increasing device complexity

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The cis electrode structure is designed to serve multiple purposes: it provides the electrical contact for current carrying, supports the redox-active polymer coating for mediator interaction, and forms part of the compartment structure. This multi-functionality reduces the need for additional separate components, limiting the increase in device complexity while maintaining membrane stability

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 solution enables the use of polarizable and non-Faradaic electrode materials without deleteriously affecting sequencing biochemistry or membranes, achieving high-throughput sensing with extended device lifetime by isolating the redox mediator species and maintaining effective ion transport.

Implementation Method 1

In an example, the mechanism to confine the redox mediator species includes an ion exchange membrane, a size selective membrane, or a redox active polymer coating

Methodology Applied
Scientific EffectIon Exchange: Ion Exchange

Implementation Method 2

In an example, the mechanism to confine the redox mediator species includes an ion exchange membrane, a size selective membrane, or a redox active polymer coating

Methodology Applied
Scientific EffectSize Selective Membrane: Semipermeable Membrane

Implementation Method 3

The nanopore sensing system also utilizes polarizable and non-Faradaic electrode materials for the cis and trans electrodes and a redox mediator species for carrying sufficient current to the respective electrodes

Methodology Applied
Scientific EffectRedox Reactions: Redox Reactions

Implementation Method 4

A polynucleotide or label/tag of an incorporated nucleotide is driven into the nanopore, changing the resistivity of the nanopore. Each nucleotide (or series of nucleotides) or each label/tag (or series of labels/tags) yields a characteristic electrical signal

Methodology Applied
Scientific EffectElectrical Resistance: Electrical Resistance

Data Source

PatentUS20230408439A1Nanopore sensing systems
Publication Date: 2023.12.21 ILLUMINA INC
  • US20230408439A1 patent drawing
  • US20230408439A1 patent drawing
  • US20230408439A1 patent drawing

AI summary

An example of a nanopore sensing system includes an application specific integrated circuit (ASIC) sensor mounted on a printed circuit board having an electrical interface with the ASIC sensor; and a nanopore sequencer formed on the ASIC sensor. The nanopore sequencer includes a redox mediator chamber having a cis electrode positioned therein; a cis well; a membrane positioned between the cis well and the redox mediator chamber, the membrane to confine a redox mediator species in the redox mediator chamber and to allow an ionic species to pass between the redox mediator chamber and the cis well; a plurality of trans wells, each including a trans electrode positioned therein; and a plurality of nanopores respectively fluidically connecting the cis well to each of the plurality of trans wells.