Voltage-Enhanced Nucleic Acid Detection on Patterned Conductive Substrates

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Solution Overview

Problem

Conventional nucleic acid array technologies are limited by inefficient loading of biological samples due to exposure to contaminants and fixed binding forces, which restrict the topological distribution and positioning of nucleic acid molecules.

Innovation Solution

The use of electrically conductive substrates with patterned attachment sites and controlled voltage application to enhance the affinity and positioning of nucleic acid molecules, allowing for precise control of electrostatic forces and varying the binding conditions for efficient analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If chemical surface treatment methods are used to create array substrates, then the substrate can be manufactured with discrete attachment sites, but the loading efficiency of biological samples is limited due to exposure to contaminants and fixed binding forces

Engineering Contradiction:
Improvesubstrate manufacturingVSAvoidloading efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent replaces chemical surface treatment methods with an electronic field-based system. A conductive substrate with patterned insulative regions creates localized electric fields that attract and concentrate nucleic acid molecules through electrostatic forces, eliminating the need for chemical surface modifications and enabling efficient loading without contaminant exposure.

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

Solution Approach 2:

The patent applies voltage to the conductive substrate to dynamically control the electrostatic attraction strength. By adjusting the voltage parameter, the binding forces between the substrate and nucleic acid molecules can be optimized for maximum loading efficiency, and the same substrate can be reused by adjusting voltage parameters for different experimental conditions.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If fixed chemical binding forces are used on the substrate surface, then nucleic acid molecules can be attached to discrete sites, but the topological distribution and positioning of molecules cannot be varied

Engineering Contradiction:
Improvediscrete site definitionVSAvoidtopological distribution control
Core Design Contradiction:
Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The patent transforms the static chemical binding system into a dynamic electronic field system. The conductive substrate with patterned insulative regions allows real-time adjustment of electric field distribution through voltage application, enabling dynamic control of nucleic acid molecule positioning and topological distribution without altering the physical substrate structure.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

By changing the voltage parameter applied to different regions of the conductive substrate, the patent can dynamically adjust the electrostatic attraction strength and spatial distribution. This allows flexible control of molecule positioning and arrangement patterns, providing adaptability for various experimental configurations while maintaining precise discrete site definition through the patterned insulative regions.

Inventive Principle:
Principle #35Parameter changes

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-density, precise analysis of nucleic acid constructs with improved efficiency in probe hybridization and sequence identification, allowing for multiple uses of the substrate and efficient data acquisition.

Implementation Method 1

the attractive forces of the binding of the biological molecules to the surface cannot be varied, since the forces are limited to the fixed, initial amine density on the surface

Methodology Applied
Scientific EffectElectrostatic forces: Electrostatics

Data Source

PatentUS9551026B2Method for nucleic acid detection using voltage enhancement
Publication Date: 2017.01.24 COMPLETE GENOMICS INC
  • US9551026B2 patent drawing
  • US9551026B2 patent drawing
  • US9551026B2 patent drawing

AI summary

Methods are provided for carrying out DNA sequencing on a device having upper and lower conductive layers separated by an insulative layer. Holes in the upper conductive layer create discrete attachment sites for DNA fragments. Voltage is applied to the surface to control affinity between the attachment sites and the DNA fragments, and to compact the DNA fragments for discrete optical detection.