Integrated Microfluidic Device for SARS-CoV-2 Detection

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Solution Overview

Problem

Current SARS-CoV-2 detection methods, such as RT-PCR, are time-consuming, labor-intensive, and require well-trained technicians, while alternative methods like antigen and antibody testing lack specificity and sensitivity, and are not suitable for early-stage detection. Additionally, existing devices for SARS-CoV-2 detection are not fully automated and require manual intervention, lacking both qualitative and quantitative detection capabilities.

Innovation Solution

An integrated microfluidic device comprising a microfluidic chip with LAMP composition, a flow control module, and a temperature control module, which automates the detection process, utilizing primers and RNA capture reagents to perform loop-mediated isothermal amplification and RNA extraction, and includes an optical detection module for fluorescence-based quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If RT-PCR is used for SARS-CoV-2 detection, then sensitivity and specificity are improved, but detection time and labor requirements increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the complex thermal cycling mechanical system of RT-PCR with an isothermal amplification system using LAMP (loop-mediated isothermal amplification) and RPA (recombinase polymerase amplification) reactions that proceed at constant temperatures (65°C for LAMP, 37°C for RPA), eliminating the need for programmable thermal cyclers and reducing detection time to under 30 minutes while maintaining high sensitivity

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

Solution Approach 2:

The patent changes the temperature parameter from variable (thermal cycling in RT-PCR) to constant (isothermal conditions in LAMP/RPA), enabling simpler device operation and faster detection. The system uses temperature control modules to maintain constant temperatures appropriate for different amplification reactions, reducing complexity while preserving detection accuracy

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If manual intervention is used in detection devices, then operational flexibility is maintained, but ease of operation and automation decrease

Engineering Contradiction:
Improveautomation levelVSAvoidsystem integration
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent merges multiple detection functions (nucleic acid extraction, amplification, and detection) into a single integrated microfluidic chip system. The chip contains integrated chambers for sample processing, magnetic bead-based extraction, LAMP/RPA amplification, and fluorescent detection, all controlled by a centralized microcontroller that automates fluid handling and data analysis, eliminating manual intervention while managing complexity through integration

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system incorporates automated fluid handling using magnetic actuation to drive reagent and sample flow through the microfluidic channels without manual pumping. Magnetic beads perform self-directed separation and concentration functions, and the microcontroller automatically analyzes fluorescent signals and generates diagnostic results, enabling the system to serve itself with minimal human input

Inventive Principle:
Principle #25Self-service

3Productivity

If antibody testing is used for SARS-CoV-2 detection, then simplicity and speed are improved, but sensitivity and early-stage detection capability deteriorate

Engineering Contradiction:
Improvedetection speedVSAvoiddetection sensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs nucleic acid amplification (LAMP/RPA) before detection, creating a large number of copies of viral genetic material from minimal starting material. This preliminary amplification step enables highly sensitive detection of early-stage infections where viral load is low, while the subsequent fluorescent detection maintains rapid results within 30 minutes

Inventive Principle:
Principle #10Preliminary action

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 enables rapid, automated, and sensitive detection of SARS-CoV-2 with high specificity, capable of both qualitative and quantitative analysis, suitable for early-stage detection and operated by ordinary personnel, reducing the need for extensive training and manual intervention.

Implementation Method 1

the chambers comprise a plurality of first functional chambers containing a loop-mediated isothermal amplification (LAMP) composition, and the LAMP composition in each of the first functional chambers comprises primers of SEQ ID NO. 1 to NO. 4

Methodology Applied
Scientific EffectLoop-mediated isothermal amplification (LAMP):

Implementation Method 2

which automates the detection process, utilizing primers and RNA capture reagents to perform loop-mediated isothermal amplification and RNA extraction, and includes an optical detection module for fluorescence-based quantification

Methodology Applied
Scientific EffectFluorescence detection: Fluorescence

Data Source

PatentUS20230226543A1Microfluidic device for SARS-COV-2 detection and method using the same
Publication Date: 2023.07.20 NATIONAL TSING HUA UNIVERSITY
  • US20230226543A1 patent drawing
  • US20230226543A1 patent drawing
  • US20230226543A1 patent drawing

AI summary

Provided is an integrated microfluidic device for SARS-CoV-2 detection. Also provided is a method for detecting SARS-CoV-2 by using the same, comprising viral lysis, RNA extraction, and reverse-transcription loop-mediated isothermal amplification (RT-LAMP). The integrated microfluidic device of the present disclosure is small in size, automatically operatable, and easy to use by ordinary people, and the present disclosure can achieve rapid detection with high sensitivity and specificity.