Single Molecule Detection via Functionalized Electrode Gaps

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Solution Overview

Problem

Current methods for detecting single molecules using electron tunneling are insensitive due to hydrocarbon contamination and require modifications that limit their versatility, making it difficult to detect molecules directly and efficiently.

Innovation Solution

A sensing device with electrodes functionalized with recognition molecules that selectively bind to target molecules, generating high contrast signals without labels, and capable of detecting single molecule binding events by monitoring current changes in a controlled gap environment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If electron tunneling is used for single molecule detection, then the detection method is simple and direct, but the sensitivity is poor due to hydrocarbon contamination on metal electrodes

Engineering Contradiction:
Improvedetection method simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces recognition molecules as intermediary layers between the metal electrodes and the target molecules. These recognition molecules have reactive groups that chemically attach to the electrodes and binding groups that specifically recognize target molecules, thereby mediating the interaction and eliminating the harmful effect of hydrocarbon contamination on electrode surfaces.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical state of the electrode surfaces by functionalizing them with recognition molecules. This transforms the electrodes from bare metal surfaces prone to hydrocarbon contamination to chemically active surfaces with specific molecular recognition capabilities, thereby improving detection sensitivity.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If molecules are chemically attached to both electrodes to form a tunnel junction, then reproducible electrical signals are obtained, but the molecule must be modified at two sites which limits versatility

Engineering Contradiction:
Improvesignal reproducibilityVSAvoiddetector versatility
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent divides the molecular bridge into two separate functional segments: recognition molecules attached to the electrodes and target molecules to be detected. This segmentation allows the recognition molecules to be modified for different targets while maintaining the same basic detector structure, thereby improving versatility.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a universal detector platform where the electrodes with attached recognition molecules can detect various different target molecules. By changing only the recognition molecule sequence or structure, the same detector can be adapted to detect different analytes, achieving multi-functionality.

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

3Adaptability or versatility

If electrode pairs are functionalized with recognition molecules that form bridges only when target molecules bind, then versatile detection is achieved, but the device cannot detect single molecules and only works with large numbers of devices

Engineering Contradiction:
Improvedetection versatilityVSAvoidnumber of molecules required for detection
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent extracts the recognition molecule function from the target molecule itself. Instead of requiring the target molecule to have specific modifications to form a bridge, the recognition molecules are pre-attached to the electrodes, allowing any target molecule with the appropriate binding site to be detected, including single molecules.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enables the detector to work with single molecules by having the recognition molecules on the electrodes self-organize and form functional bridges when a single target molecule binds between them. The system uses the binding event itself to create the conductive pathway, eliminating the need for large numbers of identical devices.

Inventive Principle:
Principle #25Self-service

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 single molecule binding events with high sensitivity, allowing for the detection of target molecules at femtomolar concentrations without the need for labels, and provides a versatile platform for various molecular species like proteins, DNA, and RNA.

Implementation Method 1

Electron tunneling is, in principle, sensitive to the presence of a molecule in a tunnel gap formed between two closely spaced metal electrodes

Methodology Applied
Scientific EffectElectron tunneling:

Data Source

PatentUS10422787B2System and method for single molecule detection
Publication Date: 2019.09.24 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US10422787B2 patent drawing
  • US10422787B2 patent drawing
  • US10422787B2 patent drawing

AI summary

A single molecule sensing or detecting device includes a first electrode and a second electrode separated from the first electrode by a gap. The first electrode and the second electrode have an opening formed therethrough. At least one of the first electrode and the second electrode is functionalized with a recognition molecule. The recognition molecule has an effective length L1 and is configured to selectively bind to a target molecule having an effective length L2. The size of the gap is configured to be greater than 2L1, but less than or equal to the sum of 2L1 and L2.