Stem-Loop Aptamer FET Sensing in Physiological Salt Conditions

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Solution Overview

Problem

Existing field-effect transistors (FETs) struggle to detect small-molecule targets under physiological, high ionic strength conditions due to biomolecule-receptor interactions occurring far from the semiconductor surface, leading to negligible changes in transconductance, and require dilute sample environments for effective detection.

Innovation Solution

Utilizing compact, highly charged oligonucleotide receptors, such as aptamers, with stem-loop structures that undergo conformational changes upon target binding, inducing conductance changes in FETs by moving closer or further from the semiconductor surface, thereby altering transconductance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If biomolecule receptors are used with FETs, then target detection capability is improved, but the sensor can only operate in dilute ionic strength samples where Debye length is increased

Engineering Contradiction:

Improvetarget detection capabilityVSAvoidoperating environment compatibility

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the physical parameters of the receptor system by using compact, highly charged oligonucleotide receptors instead of traditional large biomolecule receptors. This parameter change enables the system to function under high ionic strength conditions by reducing the Debye length requirement while maintaining detection capability through enhanced charge density and conformational sensitivity.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention applies local quality by concentrating charge density at the receptor-semiconductor interface. The compact oligonucleotide receptors with high charge density localized near the FET surface create a strong electrical signal that can be detected even when the Debye length is short, thereby enabling operation in physiological salt concentrations.

Inventive Principle:

Principle #3Local quality

2Reliability

If large biomolecule receptors like antibodies are used, then target binding capability is improved, but target detection can only occur in dilute ionic strength samples

Engineering Contradiction:

Improvetarget binding capabilityVSAvoidtransconductance change signal

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent replaces the mechanical/physical size advantage of large antibody receptors with an electrical charge-based detection mechanism. The compact oligonucleotide receptors achieve comparable or superior detection sensitivity through their high charge density and conformational changes that directly modulate the FET electrical field, eliminating the need for large physical size.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention uses composite functional properties of oligonucleotides that combine compact size, high charge density, and conformational flexibility in a single molecular system. This composite structure enables simultaneous achievement of reliable target binding and strong electrical signal generation for transconductance detection.

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If compact, highly charged oligonucleotide receptors are used, then detection in high ionic strength environments is enabled, but receptor size is reduced

Engineering Contradiction:

Improveoperating in physiological environmentsVSAvoidreceptor size

Core Design Contradiction:

Adaptability or versatilityVSLength of moving object

Solution Approach 1:

The patent applies preliminary anti-action by pre-concentrating charge density in compact oligonucleotide structures before exposure to high ionic strength environments. This pre-positioned charge density creates a strong electrical signal that counteracts the shielding effect of physiological salts, enabling detection without requiring large receptor size.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The compact oligonucleotide receptors act as intermediaries that transduce target binding events into electrical signals through conformational changes. Their high charge density serves as an amplification mechanism that compensates for their small size, enabling effective signal generation in high ionic strength conditions.

Inventive Principle:

Principle #24Intermediary (Mediator)

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

Enables direct electronic detection of small-molecule targets in high ionic strength environments without sample dilution, with enhanced sensitivity and selectivity, allowing for precise measurement of targets like glucose, dopamine, and serotonin.

Implementation Method 1

the stem region can be positioned to transform a stem-loop structure of the oligonucleotide to a new conformation that involves movement of the stem and/or capture region (loop) when the capture region binds to the target molecule

Methodology Applied

Scientific EffectConformational change:

Implementation Method 2

Such capture of a specific target can cause a change in FET transconductance

Methodology Applied

Scientific EffectField-effect transistor transconductance change:

Data Source

PatentUS12510538B2Stem-loop receptor-based field-effect transistor sensor devices for small-molecule target detection under physiological salt concentrations

Publication Date: 2025.12.30 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

Devices for detecting at least one target molecule in a sample are provided. The devices comprise a field-effect transistor and an aptamer attached to the field-effect transistor. The aptamer comprises a capture region and a stem region, wherein the target molecule can selectively bind to the capture region of the aptamer. The stem region can change a conformation of the aptamer when the capture region binds to the target molecule. Techniques for detecting a target molecule using such devices are also provided.