Nucleic Acid Sequencing Device Using Variable Electrical Field Resonance

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Solution Overview

Problem

Current DNA sequencing methods, such as the Sanger method, are impractical for integration in portable biomedical devices due to the requirement of electrophoresis, and new-generation sequencers are costly and complex, especially for target sequencing of small genome parts.

Innovation Solution

A method and device for nucleic acid sequencing that modifies the Sanger method by eliminating the electrophoresis step, using functionalized masses to bind and differentiate DNA strands based on dideoxynucleotide termination, and applying a variable electrical field to measure strand lengths through resonance conditions, enabling precise sequencing without the need for electrophoresis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If electrophoresis is used for DNA fragment separation, then sequencing accuracy is improved, but device portability and simplicity deteriorate

Engineering Contradiction:
Improvesequencing accuracyVSAvoiddevice portability
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the electrophoresis step from the traditional Sanger sequencing workflow. Instead of using electrophoresis to separate DNA fragments by size, the invention uses direct fluorescent detection of ddNTP-terminated fragments, eliminating the need for complex electrophoresis equipment and enabling portable sequencing devices.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/electrical electrophoresis system with an optical detection system. By using fluorescently labeled ddNTPs and detecting their emission directly, the invention substitutes the complex electrophoresis apparatus with a simpler fluorescent detection mechanism suitable for portable devices.

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

2Productivity

If new-generation sequencing methods are used, then throughput and speed are improved, but cost and complexity increase

Engineering Contradiction:
Improvesequencing throughputVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies partial action by focusing sequencing efforts on specific target regions rather than entire genomes. By using PCR amplification to enrich target sequences before sequencing, the method achieves high productivity for targeted applications without requiring the excessive complexity of whole-genome sequencing systems.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent changes the detection parameter from size-based separation (electrophoresis) to fluorescent label detection. This parameter change enables simultaneous detection of multiple fragments without separation, increasing throughput while simplifying the system by eliminating electrophoresis equipment.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If traditional Sanger method with electrophoresis is used, then sequencing precision is improved, but processing time and cost increase

Engineering Contradiction:
Improvesequencing precisionVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent merges the termination step and detection step into a single process. By incorporating fluorescent labels directly onto the ddNTPs themselves, the invention combines fragment termination with fluorescent marking, allowing direct detection without separate labeling and separation steps, thereby reducing processing time while maintaining precision.

Inventive Principle:
Principle #5Merging (Combining)

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 simplifies and cost-reduces DNA sequencing, allowing for precise target sequencing of small genome parts, integrating well with PCR amplification systems and providing a low-cost, portable solution for determining nucleotide sequences.

Implementation Method 1

applying a variable electrical field to measure strand lengths through resonance conditions

Methodology Applied
Scientific EffectResonance: Resonance

Implementation Method 2

using functionalized masses to bind and differentiate DNA strands based on dideoxynucleotide termination

Methodology Applied
Scientific EffectMolecular binding: Adsorption

Data Source

PatentUS10597716B2Device for nucleic acid sequencing
Publication Date: 2020.03.24 STMICROELECTRONICS SRL
  • US10597716B2 patent drawing
  • US10597716B2 patent drawing
  • US10597716B2 patent drawing

AI summary

A method for sequencing a nucleic acid strand, comprising the steps of: providing a solution containing truncated strands having lengths different from one another terminating with a respective dideoxynucleotide from among ddATP, ddTTP, ddGTP, and ddCTP; functionalizing first masses by a donor molecule and second masses by an acceptor molecule such as to generate a light emission when they come into mutual contact; coupling a first mass to a first end of each truncated strand; coupling the second masses to a respective terminal dideoxynucleotide of each strand; applying an AC electrical field having variable frequencies that are such as to generate, on each second mass, a net movement directed towards the first mass; acquiring a plurality of light radiations for each frequency value; and associating each light radiation acquired to a respective dideoxynucleotide and, thus, to a respective nucleotide base.