Nanoscale Wire Devices for Single Molecule Detection

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Solution Overview

Problem

Current nanotechnology and sub-microelectronic circuitry lack effective methods for detecting nucleic acids or other analytes at the single molecule level, particularly for determining binding constants and dissociation rates, which is crucial for identifying mismatches and dynamic information.

Innovation Solution

The development of nanoscale wire devices with immobilized binding partners, where a metal-semiconductor compound is used to detect changes in conductivity due to the association and dissociation of nucleic acids, allowing for the determination of binding constants and dissociation rates, and identifying mismatches between nucleic acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional nanotechnology and sub-microelectronic circuitry are used, then device fabrication is achieved, but detection of nucleic acids at the single molecule level is not possible

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection capability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes the physical parameters of the detection system by using nanoscale wires with dimensions in the 1-100 nm range, which provides sufficient surface area to volume ratio for single molecule detection while maintaining electrical conductivity for signal transduction

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite structures combining nanoscale wires with binding partners (such as antibodies or nucleic acids) to create a hybrid system that兼具 electrical detection capability and specific molecular recognition function

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If nanoscale wire devices with immobilized binding partners are used, then binding constants and dissociation rates can be determined, but device complexity increases

Engineering Contradiction:
Improvebinding constant determinationVSAvoiddevice structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the nanoscale wire into distinct functional segments: one region for immobilizing binding partners and another region for electrical contact, allowing independent optimization of each function while simplifying the overall device design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses binding partners as intermediary molecules that specifically recognize target analytes and transduce this recognition into electrical signals through their association/dissociation kinetics, simplifying the detection mechanism

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If metal-semiconductor compounds are used to detect conductivity changes, then single base mismatches can be detected, but manufacturing precision requirements increase

Engineering Contradiction:
Improvemismatch detectionVSAvoidnanoscale wire fabrication
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent applies different material properties to different regions of the nanoscale wire: metal-semiconductor compounds are used specifically at contact points for electrical connection, while other regions maintain semiconductor properties for binding partner immobilization and detection

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

Enables the detection of single base mismatches and dynamic information at the single molecule level with high sensitivity, facilitating the identification of nucleic acid mismatches and kinetic analysis.

Implementation Method 1

a metal-semiconductor compound is used to detect changes in conductivity due to the association and dissociation of nucleic acids

Methodology Applied
Scientific EffectElectrical conductivity change: Conduction (electrical)

Data Source

PatentUS9903862B2Nanosensors and related technologies
Publication Date: 2018.02.27 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US9903862B2 patent drawing
  • US9903862B2 patent drawing
  • US9903862B2 patent drawing

AI summary

The present invention generally relates to nanotechnology and sub-microelectronic circuitry, as well as associated methods and devices, for example, nanoscale wire devices and methods for use in determining nucleic acids or other analytes suspected to be present in a sample. For example, a nanoscale wire device can be used in some cases to detect single base mismatches within a nucleic acid. In one aspect, dynamical information such as a binding constant, an association rate, and/or a dissociation rate, can be determined between a nucleic acid or other analyte, and a binding partner immobilized relative to a nanoscale wire. In some cases, the nanoscale wire includes a first portion comprising a metal-semiconductor compound, and a second portion that does not include a metal-semiconductor compound. The binding partner, in some embodiments, is immobilized relative to at least the second portion of the nanoscale wire.