Microfluidic Electrostatic Capture for Nucleic Acid Concentration

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Solution Overview

Problem

Current microfluidic devices are ineffective in efficiently extracting and concentrating low-abundance nucleic acids, such as miRNAs, from biological fluids at high flow rates, making them unsuitable for clinical applications due to high costs, time-consuming processes, and complexity, particularly for point-of-care diagnostics.

Innovation Solution

The development of microfluidic devices with electrically insulating substrates and electrodes that create electrostatic forces to capture and concentrate nucleic acids within microfluidic channels, allowing for high flow rates and efficient concentration of molecules without the need for PCR amplification, using electrostatic interactions and dielectrophoretic forces to immobilize and release nucleic acids into smaller chambers for detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microfluidic devices are used to extract and concentrate nucleic acids, then the extraction process can be performed, but the devices are ineffective at high flow rates and require time-consuming processes with low efficiency

Engineering Contradiction:
Improveextraction efficiencyVSAvoidprocessing time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent replaces conventional mechanical extraction methods with electrostatic field-based capture mechanisms. Electrodes generate electric fields that create electrostatic forces to rapidly capture and concentrate nucleic acids, eliminating the need for time-consuming mechanical steps while maintaining high extraction efficiency even at elevated flow rates

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

2Measurement precision

If PCR amplification is used to detect low-abundance nucleic acids, then detection sensitivity can be improved, but the process becomes more complex and time-consuming

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent performs preliminary concentration of nucleic acids using electrostatic capture before detection. By pre-concentrating the target molecules in a small volume within the microfluidic channel, the system achieves detection sensitivity comparable to or exceeding PCR amplification without requiring the complex amplification steps, thereby simplifying the overall detection process

Inventive Principle:
Principle #10Preliminary action

3Reliability

If conventional extraction methods are used, then nucleic acids can be extracted, but the process is costly and complex for point-of-care applications

Engineering Contradiction:
Improveextraction effectivenessVSAvoiddevice simplicity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent implements local electrostatic capture zones within the microfluidic channel where electrodes are positioned to create focused electric fields. This localized approach allows effective nucleic acid extraction to occur in specific regions while maintaining a simple overall device structure suitable for point-of-care manufacturing and deployment

Inventive Principle:
Principle #3Local quality

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

These devices achieve a 1000-fold increase in nucleic acid concentration, enabling sensitive and rapid detection of miRNAs and other biomolecules, suitable for early disease diagnosis, including cancers, with minimal invasiveness and cost-effectiveness, outperforming conventional methods in terms of throughput and efficiency.

Implementation Method 1

the array of electrodes are operable to produce an electric field across the microfluidic channel that creates an electrostatic attractive force on the nucleic acids to immobilize them in the capture region

Methodology Applied
Scientific EffectElectrostatic attractive force: Electrostatics

Implementation Method 2

using electrophoretic effects... electrostatic interactions and dielectrophoretic forces to immobilize and release nucleic acids

Methodology Applied
Scientific EffectDielectrophoretic forces:

Implementation Method 3

a filter region in the microfluidic channel between the first chamber region and the second chamber region and structured to include holes of a size preventing the particles to pass but allowing the nucleic acids to pass through

Methodology Applied
Scientific EffectSize-based filtration: Filter (physical)

Data Source

PatentUS9994839B2Microfluidic devices to extract, concentrate and isolate molecules
Publication Date: 2018.06.12 RGT UNIV OF CALIFORNIA
  • US9994839B2 patent drawing
  • US9994839B2 patent drawing
  • US9994839B2 patent drawing

AI summary

Methods, systems, and devices are disclosed for capturing, concentrating, and isolating molecules in a fluid. In one aspect, a device includes a substrate formed of a material that is electrically insulating, a microfluidic channel made of an electrically insulating material formed on the substrate to carry a biofluid containing molecules including nucleic acids, an array of electrodes formed on the surface along a parallel direction of the microfluidic channel constituting a capture region, in which the array of electrodes are operable to produce an electric field across the microfluidic channel that creates an electrostatic attractive force on the nucleic acids to immobilize them in the capture region, and a chamber formed on the substrate of the electrically insulating material and connected to the microfluidic channel, the chamber configured to have a volume less than that of the microfluidic channel, in which, when the nucleic acids are released from immobilization in the capture region, the released nucleic acids are collected in the chamber.