Stimuli-Responsive Heteropolymer Flow Cell for Specific Hybridization

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Solution Overview

Problem

Existing biological arrays face challenges in efficiently detecting and analyzing longer nucleotide sequences due to limitations in probe hybridization and signal detection, particularly in genetic sequencing and molecular detection applications.

Innovation Solution

The development of a switchable heteropolymer with stimuli-responsive functional groups that change polarity and conformation in response to predetermined stimuli, such as pH, temperature, saccharides, nucleophiles, or salts, allowing for improved hybridization and signal detection in flow cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional biological arrays are used for detecting longer nucleotide sequences, then the array structure remains simple, but the detection efficiency and accuracy deteriorate

Engineering Contradiction:

Improvedetection efficiencyVSAvoiddetection accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies parameter changes by modifying the physical and chemical properties of the array surface through heteropolymer coatings with stimuli-responsive functional groups. These polymers change their conformation, polarity, or charge state in response to pH, temperature, or ionic strength changes, thereby dynamically optimizing probe hybridization efficiency and reducing non-specific binding for improved detection of longer sequences

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining multiple types of functional groups within a single heteropolymer structure. The heteropolymer includes a mixture of charged groups (carboxylate, sulfonate), polar groups (hydroxyl, amide), and stimuli-responsive groups that work synergistically to enhance both the efficiency and accuracy of nucleotide sequence detection

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If probe hybridization is optimized for longer sequences, then detection accuracy improves, but non-specific adsorption increases

Engineering Contradiction:

Improvehybridization specificityVSAvoidnon-specific adsorption

Core Design Contradiction:

Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent implements dynamics through stimuli-responsive heteropolymers that can dynamically adjust their conformation and binding properties in response to environmental changes. The polymers transition between different states (e.g., collapsed/expanded, charged/neutral) based on pH, temperature, or ionic strength, allowing real-time optimization of specific hybridization while minimizing non-specific adsorption

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent applies local quality by creating heterogeneous surfaces with regions of different chemical properties within the heteropolymer coating. Different functional groups are distributed throughout the polymer structure, providing localized zones for specific hybridization, repulsion of non-specific binding, and controlled adsorption, thereby enhancing specificity while reducing harmful non-specific interactions

Inventive Principle:

Principle #3Local quality

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

Enhances the efficiency and accuracy of genetic sequencing and molecular detection by optimizing probe hybridization and signal detection, reducing non-specific adsorption, and improving sequencing metrics.

Implementation Method 1

a pH-responsive functional group selected from the group consisting of a hydroxyl, 1,2-diol, 1,3-diol protected as an acetal, hemiacetal, or ketal, a tert-butyloxycarbonylamino group, a 9H-fluoren-9-ylmethoxycarbonylamino group, an amino group, a carboxylate group, a carboxylic acid group, a sulfonate group, and a sulfonic acid group

Methodology Applied

Scientific EffectpH-responsive functional group modification:

Implementation Method 2

a temperature-responsive group includes a heat-sensitive hydroxyl or amino protecting group

Methodology Applied

Scientific EffectTemperature-responsive functional group modification:

Implementation Method 3

the stimuli-responsive functional group is capable of undergoing modification when exposed to a predetermined stimulus, wherein the modification changes the polarity and/or conformation of the switchable heteropolymer

Methodology Applied

Scientific EffectConformation change in response to stimulus:

Implementation Method 4

Enhances the efficiency and accuracy of genetic sequencing and molecular detection by optimizing probe hybridization and signal detection

Methodology Applied

Scientific EffectHybridization enhancement:

Implementation Method 5

reducing non-specific adsorption

Methodology Applied

Scientific EffectNon-specific adsorption reduction:

Data Source

PatentUS12359053B2Flow cell including a heteropolymer

Publication Date: 2025.07.15 ILLUMINA INC

AI summary

A flow cell includes a support and a heteropolymer attached to the support. The heteropolymer includes an acrylamide monomer including an attachment group to react with a functional group attached to a primer, and a monomer including a stimuli-responsive functional group. The monomer including the stimuli-responsive functional group may be pH-responsive, temperature-responsive, saccharide-responsive, nucleophile-responsive, and/or salt-responsive.