Molecular Pore Sequencing With Sequential Analyte Membrane Coupling

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Solution Overview

Problem

Existing polynucleotide sequencing technologies are slow and expensive due to reliance on amplification techniques and high quantities of fluorescent chemicals, requiring significant amounts of analyte for detection.

Innovation Solution

A method for determining the presence, absence, or characteristics of multiple analytes by successively coupling them to a membrane with a detector, allowing interaction, and uncoupling to achieve ultra-low concentration detection, utilizing anchors and cyclodextrin for uncoupling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If amplification techniques and high quantities of fluorescent chemicals are used for polynucleotide sequencing, then detection sensitivity is improved, but cost and time consumption increase

Engineering Contradiction:

Improvedetection sensitivityVSAvoidsequencing speed

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent extracts the essential detection function from complex amplification techniques and fluorescent chemical systems, using instead a simplified nanopore-based detection method that directly senses polynucleotide molecules without requiring amplification or expensive fluorescent labels, thereby maintaining detection sensitivity while dramatically reducing cost and time

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the chemical-based fluorescent detection system with an electrical measurement system using nanopores, where ionic current changes detect polynucleotide presence and characteristics, eliminating the need for fluorescent chemicals and amplification while improving sequencing throughput

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If high quantities of analyte are used for detection, then detection reliability is improved, but cost and sample requirements increase

Engineering Contradiction:

Improvedetection reliabilityVSAvoidanalyte concentration

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the detection parameter from optical fluorescence intensity to electrical ionic current measurement through nanopores, enabling reliable detection at ultra-low analyte concentrations (as low as 0.001 pM) by measuring conductance changes as individual polynucleotide molecules pass through the nanopore

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses nanopores as the detection medium, where the nanoscale pore structure concentrates and interacts with individual polynucleotide molecules, amplifying the electrical signal from single molecules and enabling reliable detection without requiring high analyte concentrations

Inventive Principle:

Principle #31Porous materials

3Productivity

If multiple analytes are detected simultaneously, then throughput is improved, but measurement interference increases

Engineering Contradiction:

Improvedetection throughputVSAvoidmeasurement accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the detection process into sequential steps: coupling different analytes to the membrane at different times, allowing each analyte to be detected individually in separate measurement cycles, thereby maintaining high throughput while eliminating cross-interference between multiple analyte types

Inventive Principle:

Principle #1Segmentation

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

Reduces the required analyte concentration by several orders of magnitude, enabling efficient sequencing and detection of polynucleotides at concentrations as low as 0.001 pM, increasing sequencing efficiency and accuracy, and allowing multiple analytes to be detected without simultaneous measurement interference.

Implementation Method 1

coupling a first analyte in a first sample to a membrane using one or more anchors

Methodology Applied

Scientific EffectBinding interaction: Adsorption

Implementation Method 2

allowing the first analyte to interact with a detector present in the membrane and thereby determining the presence, absence or one or more characteristics of the first analyte

Methodology Applied

Scientific EffectAnalyte-detector interaction:

Implementation Method 3

a method for uncoupling from a membrane an analyte coupled to the membrane using cholesterol, comprising contacting the analyte with a cyclodextrin or a derivative thereof

Methodology Applied

Scientific EffectCyclodextrin-cholesterol interaction: Solvation

Data Source

PatentUS12571035B2Method of target molecule characterisation using a molecular pore

Publication Date: 2026.03.10 OXFORD NANOPORE TECH LTD

AI summary

The invention relates to a new method of determining the presence, absence or one or more characteristics of multiple analytes. The invention concerns coupling a first analyte to a membrane containing a detector and investigating the first analyte using the detector. The invention also concerns coupling a second analyte to the membrane and investigating the second analyte. The first analyte is uncoupled form the membrane prior to investigating the second analyte. The invention also relates to polynucleotide sequencing.