Capillary Microfluidic Device for Nucleic Acid Concentration

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Solution Overview

Problem

Current point-of-care diagnostics devices face challenges in efficiently processing and concentrating nucleic acids from large sample volumes, requiring external instrumentation and complex sample handling, which limits their usability in resource-limited settings and simplifies the integration of sample preparation, amplification, and detection.

Innovation Solution

A capillary-driven microfluidic device that uses a slider mechanism with a porous membrane for solid-phase extraction and isothermal enzymatic amplification, allowing for the concentration of nucleic acids through wicking action, eliminating the need for pumps, valves, and manual pipetting, and enabling real-time fluorescence detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If nucleic acids are extracted and concentrated from large sample volumes using conventional methods (spin columns and centrifuges), then the nucleic acid concentration and purity are improved, but the device complexity and need for external instrumentation increase

Engineering Contradiction:
Improvenucleic acid concentrationVSAvoiddevice complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent combines multiple functions (extraction, concentration, purification) into a single integrated microfluidic device. The microfluidic chip integrates the porous membrane extraction medium, wicking pads, and reaction chambers into one compact unit, eliminating the need for separate spin columns and centrifuges while achieving the same nucleic acid concentration and purity goals.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The device uses capillary action through wicking pads to automatically draw liquids through the porous membrane and transport extracted nucleic acids to reaction chambers without requiring external centrifuges or pumps. The system self-regulates fluid flow based on capillary forces, eliminating the need for complex external instrumentation.

Inventive Principle:
Principle #25Self-service

2Measurement precision

If sample processing steps are separated and performed manually, then the detection precision is improved, but the operator intervention and time consumption increase

Engineering Contradiction:
Improvedetection precisionVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The microfluidic device enables continuous automated processing where lysate is continuously drawn through the porous membrane by wicking action, and extracted nucleic acids are continuously transported to reaction chambers. This continuous flow process eliminates manual intervention steps while maintaining detection precision through controlled capillary-driven fluid movement.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The wicking pad acts as an intermediary component that automatically mediates the transfer of extracted nucleic acids from the porous membrane to the reaction chamber. This intermediary mechanism eliminates the need for manual pipetting while ensuring precise delivery of nucleic acids to the amplification reaction.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If large sample volumes are processed to detect low viral loads, then the detection sensitivity is improved, but the reaction volume and enzyme consumption increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidenzyme consumption
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The device extracts and concentrates nucleic acids from large sample volumes (e.g., 500 µL) into a small elution volume using the porous membrane and wicking pad system. This extraction and concentration step allows subsequent amplification reactions to use minimal enzyme quantities while maintaining high detection sensitivity for low viral loads.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The porous membrane provides localized high-affinity binding sites for nucleic acid extraction, concentrating the target analyte in a specific location (the elution buffer at the membrane interface). This localized concentration enables sensitive detection with minimal reaction volumes and enzyme consumption.

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

The device effectively concentrates nucleic acids from large sample volumes into smaller reaction volumes, facilitating sensitive and specific detection, and simplifies the diagnostic process by integrating sample preparation and amplification, reducing operator intervention and the need for external equipment.

Implementation Method 1

a porous membrane for solid-phase extraction

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

concentration of nucleic acids through wicking action

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS11986820B2Point-of-care diagnostic methods using capillary-action microfluidic devices
Publication Date: 2024.05.21 MAUK MICHAEL G
  • US11986820B2 patent drawing
  • US11986820B2 patent drawing
  • US11986820B2 patent drawing

AI summary

Methods that integrates processing and an analysis of a sample are disclosed and include use of a testing device that integrates nucleic acid isolation, isothermal amplification and detection wherein a sample and reagents are transported through a capture/binding membrane by capillary forces and the positioning of a slidebar that supports said binding membrane. In the practice of the methods, flow control and fluid actuation are effected by the position of a slidebar of the device which makes a fluidic connection through the capture membrane situated between a reservoir of liquid on the device and an absorbing pad, and where a sequence of operations for sample loading, washing, optionally amplification, and optical detection of analytes can be done conveniently and rapidly at the point of care.