Nucleic Acid Sequencer Using Atomically Thin Membrane Capacitance

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Solution Overview

Problem

Current nucleic acid sequencing technologies face challenges in achieving fast and accurate determination of single-stranded nucleic acid sequences, particularly in efficiently detecting nitrogenous bases using capacitive displacement methods.

Innovation Solution

The development of a nucleic acid sequencer utilizing an atomically thin membrane in a capacitive configuration with a solid electrode, where a complementary base covalently disposed on the membrane forms base pairs with nitrogenous bases, causing the membrane to flex and change capacitance, allowing for ultra-fast and accurate sequence determination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional sequencing methods are used, then sequencing can be performed with established technologies, but the speed and accuracy of determining single-stranded nucleic acid sequences is insufficient

Engineering Contradiction:
Improveaccuracy of sequence determinationVSAvoidsequencing speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces conventional mechanical/optical sequencing methods with an electrical field-based detection system. A solid electrode generates an electrical field that interacts with the atomically thin membrane, causing it to flex in response to base pairing forces. This electrical field interaction enables simultaneous high-speed and high-precision detection of nitrogenous bases, resolving the contradiction between sequencing speed and accuracy.

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

Solution Approach 2:

The patent changes the detection parameter from conventional optical or mechanical measurements to electrical field-induced membrane flexing. By measuring the capacitance changes or current variations in the electrical field as the membrane flexes during base pairing, the system achieves both ultra-fast response times and high measurement precision, enabling millions of bases to be sequenced per second with increased accuracy.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If atomically thin membrane is used in capacitive configuration, then ultra-fast and accurate sequence determination is enabled, but device complexity increases

Engineering Contradiction:
Improvesequencing throughputVSAvoidcomplexity of capacitive sensor structure
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs an atomically thin membrane as a flexible sensing element that can be integrated into a capacitive configuration with a solid electrode. This thin film structure enables ultra-fast response to base pairing events while maintaining a relatively simple overall device architecture. The membrane's flexibility allows it to respond dynamically to molecular interactions, achieving high throughput sequencing without excessive device complexity.

Inventive Principle:
Principle #30Flexible shells and thin films

3Measurement precision

If complementary base forms base pairs with nitrogenous base causing membrane to flex, then accurate base detection is achieved, but the force required may affect membrane stability

Engineering Contradiction:
Improveaccuracy of base detectionVSAvoidstability of atomically thin membrane
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent applies a preliminary electrical field to the atomically thin membrane before base pairing occurs. This pre-applied electrical field stabilizes the membrane structure and prepares it for the mechanical stress of base pairing. By establishing the electrical field in advance, the membrane is primed to respond to base pairing forces without compromising its structural integrity, enabling accurate base detection while maintaining membrane stability throughout the sequencing process.

Inventive Principle:
Principle #10Preliminary action

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 high-throughput, cost-effective sequencing of millions of bases per second with increased accuracy and scalability, leveraging the flexibility and conductivity of materials like graphene and molybdenum disulfide to detect base pairs and produce distinct electrical signals for sequence identification.

Implementation Method 1

arranged in a capacitive configuration with the atomically thin membrane... such that an amount of the electric current changes in response to a change in the selected distance between the atomically thin membrane and the solid electrode

Methodology Applied
Scientific EffectCapacitance: Capacitance

Implementation Method 2

complementary base covalently disposed on the atomically thin membrane and arranged to base pair with a nitrogenous base of the single stranded nucleic acid

Methodology Applied
Scientific EffectHydrogen bonding:

Data Source

PatentUS10381107B2Nucleic acid sequencer for electrically determining a sequence of nitrogenous bases in a single stranded nucleic acid
Publication Date: 2019.08.13 THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE COMMERCE
  • US10381107B2 patent drawing
  • US10381107B2 patent drawing
  • US10381107B2 patent drawing

AI summary

A nucleic acid sequencer includes: an atomically thin membrane; a solid electrode spaced apart from the atomically thin membrane and arranged in a capacitive configuration with the atomically thin membrane; a spacer member; a complementary base covalently disposed on the atomically thin membrane and arranged to base pair with a nitrogenous base of the single stranded nucleic acid; a power source in electrical communication with the solid electrode and that provides electrical power to the solid electrode; and a resistor in electrical communication with the power source and that receives electric current from the power source and that also is in electrical communication with the atomically thin membrane such that an amount of the electric current changes in response to a change in the selected distance between the atomically thin membrane and the solid electrode.