Nanoscale Electrode Arrays for Molecular Sequencing

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Solution Overview

Problem

Current methods for sequencing DNA, RNA, and protein molecules require large and expensive instrumentation due to the difficulty in defining conducting structures with dimensions smaller than 2 nm, necessitating the use of high-resolution lithographic instruments and sensitive optical or electrochemical detection systems.

Innovation Solution

The development of nanoscale electrodes and microfluidic channels integrated with CMOS electronics allows for direct electrical conductivity and capacitance measurements of molecules, enabling sequencing without additional amplifiers or detection electronics, and reducing the overall size of sequencing systems through microelectronic fabrication techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If lithographic fabrication is used to define conducting structures, then manufacturing precision can be maintained down to 5 nm, but it becomes very difficult to define conducting structures with dimensions below 2 nm

Engineering Contradiction:
Improveconducting structure dimensionVSAvoidfabrication difficulty
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent replaces lithographic fabrication (mechanical/optical system) with a self-assembly approach using block copolymers. The block copolymer molecules spontaneously organize into periodic structures with nanoscale precision through thermodynamic self-organization, eliminating the need for complex lithographic tools and achieving dimensions below 2 nm that are difficult to obtain through conventional lithography.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If expensive and large sequencers are used for molecular sequencing, then measurement precision and reliability are improved, but device size and cost increase significantly

Engineering Contradiction:
Improvesequencing accuracyVSAvoidsystem size
Core Design Contradiction:
Measurement precisionVSVolume of moving object

Solution Approach 1:

The patent merges multiple previously separate components into a single integrated device: the block copolymer template structure serves simultaneously as the electrode pattern definition, the insulator layer, and the structural framework. The conducting material is deposited conformally onto this template, creating an integrated nanoscale electrode array that eliminates the need for separate lithographic steps and large sequencing instrumentation.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent employs a hierarchical nested structure where block copolymer blocks are nested within micelle structures, which are nested within the microfluidic device architecture. The conducting material is nested conformally onto the block copolymer template. This nested arrangement achieves high-density nanoscale electrodes while maintaining a compact overall device footprint.

Inventive Principle:
Principle #7Nested doll (Nesting)

3Difficulty of detecting and measuring

If additional amplifiers or detection electronics are added to interrogate molecules, then measurement sensitivity is improved, but device complexity and size increase

Engineering Contradiction:
Improvemolecule detection sensitivityVSAvoidelectronics complexity
Core Design Contradiction:
Difficulty of detecting and measuringVSDevice complexity

Solution Approach 1:

The block copolymer structure serves itself as both the template and the functional element. The self-assembled periodic structure of the block copolymers creates the electrode pattern without requiring external lithographic tools or additional fabrication steps. The structure inherently provides the nanoscale precision needed for sensitive molecular interrogation without adding complex electronics.

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

This approach enables the radical reduction in size of sequencing systems, allowing for efficient and reliable sequencing of long-chain molecules using nanoscale electrodes and microfluidic channels, providing accurate identification of molecular components without the need for expensive amplifiers or sensitive optics.

Implementation Method 1

direct electrical conductivity and capacitance measurements can be conducted on the molecules of interest

Methodology Applied
Scientific EffectElectrical conductivity measurement: Conduction (electrical)

Implementation Method 2

direct electrical conductivity and capacitance measurements can be conducted on the molecules of interest

Methodology Applied
Scientific EffectCapacitance measurement: Capacitance

Data Source

PatentUS20230097858A1Systems and methods for molecular measurements
Publication Date: 2023.03.30 CALIFORNIA INST OF TECH
  • US20230097858A1 patent drawing
  • US20230097858A1 patent drawing
  • US20230097858A1 patent drawing

AI summary

Systems and methods for identifying the components of a long-chain molecule by making electrical measurements from fabricated nanoscale electrodes as the molecule moves down a narrow microfluidic channel. The channel can be along the surface of a chip, through a chip, or both.