Nucleic Acid Probe Strand Exchange for Chemical Sensor Sensitivity

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Solution Overview

Problem

Current chemical sensors face challenges in achieving high sensitivity and stability while detecting target substances, as they often struggle to balance high binding ability with significant signal output and detection at concentrations below the dissociation constant.

Innovation Solution

A chemical sensor utilizing a nucleic acid probe with a metastable structure formed by a short-chain complementary chain, which undergoes a strand exchange reaction upon target substance capture, enhancing detection sensitivity and stability through a specific binding site mechanism.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a nucleic acid probe with high binding ability is used to detect target substances, then detection sensitivity is improved, but signal output and stability deteriorate due to inability to achieve significant signal change at concentrations below dissociation constant

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsignal stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The nucleic acid probe employs a dynamic structure-switching mechanism where the probe transitions from an open single-stranded configuration to a closed double-stranded structure upon target binding. This dynamic conformational change amplifies the signal by altering the probe's physical state, enabling detection at concentrations below the dissociation constant while maintaining stability through the thermodynamically favorable double-stranded formation.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the structural parameter of the nucleic acid probe from a static binding configuration to a dynamic structure that undergoes conformational transition. The probe's secondary structure changes upon target binding, transforming the binding event into a measurable structural parameter change that enhances signal output and stability simultaneously.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If a nucleic acid probe is designed to bind target substances at low concentrations, then detection sensitivity is improved, but binding stability deteriorates due to weak affinity at sub-dissociation constant levels

Engineering Contradiction:
Improvedetection limitVSAvoidbinding stability
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The probe utilizes a dynamic structure-switching mechanism where binding at low concentrations triggers a conformational transition to a stable double-stranded structure. This dynamic process allows the probe to achieve high detection sensitivity at sub-dissociation constant concentrations while maintaining binding stability through the thermodynamic stability of the formed double-stranded structure.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The probe is pre-designed with a complementary sequence and secondary structure that are primed to undergo a conformational change upon target binding. This preliminary structural arrangement ensures that even weak initial binding events at low concentrations can trigger the stabilizing structure switch, thereby achieving both low detection limits and binding stability.

Inventive Principle:
Principle #10Preliminary action

3Strength

If a nucleic acid probe with high affinity for target substances is used, then binding ability is improved, but signal output deteriorates due to lack of significant conformational change

Engineering Contradiction:
Improvebinding abilityVSAvoidsignal output
Core Design Contradiction:
StrengthVSMeasurement precision

Solution Approach 1:

The probe is designed with high affinity binding capability combined with a dynamic structure-switching mechanism. Upon target binding, the probe transitions from an open single-stranded state to a closed double-stranded structure, generating a significant conformational change that produces a measurable signal. This dynamic transition amplifies the signal output while maintaining high binding ability.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention couples high-affinity binding with a measurable structural parameter change. The probe's secondary structure serves as a signal transduction element that changes upon binding, transforming the binding event into a detectable physical change and thereby enhancing signal output without compromising binding strength.

Inventive Principle:
Principle #35Parameter changes

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

The sensor effectively detects target substances at concentrations lower than the dissociation constant, with a stable higher-order structure and reversible binding, enabling improved detection sensitivity and signal output.

Implementation Method 1

A chemical sensor utilizing a nucleic acid probe with a metastable structure formed by a short-chain complementary chain, which undergoes a strand exchange reaction upon target substance capture

Methodology Applied
Scientific EffectStrand exchange reaction: Chemical Bonding

Implementation Method 2

The nucleic acid probe is a double-stranded nucleic acid composed of a first nucleic acid and a second nucleic acid bound to the first nucleic acid

Methodology Applied
Scientific EffectComplementary base pairing: Chemical Bonding

Data Source

PatentUS20240110229A1Chemical sensor using strand exchange reaction
Publication Date: 2024.04.04 KK TOSHIBA
  • US20240110229A1 patent drawing
  • US20240110229A1 patent drawing
  • US20240110229A1 patent drawing

AI summary

According to one embodiment, a chemical sensor including a nucleic acid probe for capturing a target substance, a sensor element that has a surface on which the nucleic acid probe is immobilized, and a liquid film that covers the sensor element is provided.