Multi-Phase Nucleic Acid Sequencing via Debye Layer Coupling

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Solution Overview

Problem

Current nucleic acid sequencing technologies are expensive and lack the speed and accuracy needed for rapid, high-throughput DNA sequencing, particularly for clinical applications, limiting their effectiveness in diagnosing and treating genetic diseases and infectious diseases.

Innovation Solution

The method involves using a system with multiple electrodes and fluidic delivery systems to detect biological molecules by coupling them to a Debye layer, switching between different solutions with varying polymerase types, ion concentrations, and conditions to leverage biases for improved sequencing accuracy and length, and using computer processors to analyze data sets from different detection phases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing sequencing technology is used, then sequencing can be performed, but the cost is expensive and accuracy/speed are insufficient for clinical applications

Engineering Contradiction:
Improvesequencing accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system segments the sequencing process into multiple independent detection phases, each using different sequencing conditions (different polymerases, buffer compositions, temperatures). Each phase targets specific sequence regions with different biases, and the results are computationally integrated to achieve high-accuracy whole-genome sequencing without requiring a single complex high-cost system

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes multiple parameters including polymerase type, buffer composition, ionic strength, pH, and temperature across different detection phases. These parameter variations create different sequence detection biases that, when combined, overcome the limitations of any single condition and achieve both high accuracy and cost-effectiveness

Inventive Principle:
Principle #35Parameter changes

2Productivity

If existing sequencing technology is used, then sequencing can be performed, but the speed and throughput are insufficient for rapid diagnostics

Engineering Contradiction:
Improvesequencing throughputVSAvoidsequencing accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system employs periodic action by cycling through multiple detection phases with different sequencing conditions. Each phase is optimized for specific sequence characteristics, and the periodic switching between conditions allows rapid accumulation of sequence data with high accuracy without requiring excessive total sequencing time

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The invention merges results from multiple detection phases with different biases into a unified high-accuracy sequence. By combining data from phases using different polymerases and conditions, the system achieves both high throughput and high accuracy that would be unattainable with any single sequencing run

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If single sequencing condition is optimized, then one parameter may be improved, but other parameters such as read length and accuracy suffer from biases

Engineering Contradiction:
Improvesequence accuracyVSAvoidcondition flexibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The system achieves universality by designing a multi-functional detection platform that can operate under multiple sequencing conditions using the same core technology. A single system can perform sequencing with different polymerases, buffer compositions, and temperatures, making it adaptable to various sequence types and requirements while maintaining high accuracy across all conditions

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

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 higher quality sequencing with longer read lengths and increased accuracy, reducing costs and time, making it more suitable for clinical applications and improving diagnostics.

Implementation Method 1

coupling the biological molecule to the Debye layer of a plurality of electrodes such that the plurality of electrodes and the biological molecule provide an electrical current flow path for detecting a signal indicative of the biological molecule or the biological reaction

Methodology Applied
Scientific EffectDebye layer coupling: Electrical Impedance Tomography

Data Source

PatentUS11015219B2Systems and methods for detection and analysis of biological species
Publication Date: 2021.05.25 SEQUENCING HEALTH INC
  • US11015219B2 patent drawing
  • US11015219B2 patent drawing
  • US11015219B2 patent drawing

AI summary

Provided herein are systems and methods for sequencing, amplifying, detecting, analyzing, and/or performing sample preparation procedures for nucleic acids and other biomolecules.