Integrated Microfluidic Nucleic Acid Analysis System

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Solution Overview

Problem

Current nucleic acid diagnostics lack a multiplex, automated, integrated 'sample to result' system capable of processing raw biological samples, particularly for point-of-care applications, and no commercial instruments are available for field-portable nucleic acid processing.

Innovation Solution

A portable, integrated, and automated biodetection system that performs parallel detection of distinct nucleic acid sequences through multiple sequence amplification and simultaneous hybridization readout, utilizing microfluidic connection for sample lysis, purification, PCR, and detection modules with evanescent wave excitation and temperature-controlled hybridization, and is configured for rapid, multiplex analysis of various sample types.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a multiplex automated integrated system is developed for sample-to-result nucleic acid analysis, then productivity and analysis capability are improved, but device complexity increases

Engineering Contradiction:
Improveanalysis capabilityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent integrates multiple previously separate functions (sample preparation, amplification, and detection) into a single automated system. The system combines lysis, purification, PCR amplification, and microarray detection modules into one integrated platform that can simultaneously analyze multiple nucleic acid targets from a single sample, thereby improving productivity while managing complexity through functional consolidation

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The developed system serves multiple functions within a single platform: it can process various sample types (blood, saliva, environmental samples), perform different amplification reactions (PCR, reverse transcription), and detect multiple nucleic acid targets simultaneously through microarray hybridization. This multi-functionality allows the system to replace several separate devices, improving overall productivity despite the inherent complexity of integrating these diverse capabilities

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

2Ease of operation

If field-portable nucleic acid processing is implemented, then ease of operation and accessibility are improved, but manufacturing precision and reliability become more difficult to maintain

Engineering Contradiction:
ImproveportabilityVSAvoidprocessing precision
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The system is designed as a portable, self-contained unit that segments the complex nucleic acid analysis process into integrated modules (lysis, purification, amplification, detection) that can function together in a field-deployable format. This segmentation allows the system to be transported and operated in diverse locations while maintaining processing precision through controlled, automated operations within each module

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The automated system performs all critical functions without requiring skilled operators for each step. The integrated platform automatically executes sample processing, amplification, and detection protocols, reducing human error and maintaining manufacturing precision even when operated in field conditions by personnel without specialized training

Inventive Principle:
Principle #25Self-service

3Loss of time

If rapid analysis is achieved with results in under 120 minutes, then time efficiency is improved, but duration of each processing step must be optimized which increases complexity

Engineering Contradiction:
Improveanalysis timeVSAvoidprocess control complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The system implements continuous automated processing where sample lysis, purification, amplification, and detection occur in seamless succession without manual intervention between steps. The integrated design allows reactions to proceed continuously through connected modules, eliminating idle time and reducing total analysis time to under 120 minutes while the automation manages the complexity of coordinating these continuous processes

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

Sample preparation steps including lysis and purification are performed automatically and continuously as preliminary actions before amplification begins. The system pre-processes samples through integrated modules, ensuring they are ready for rapid amplification and detection, thereby reducing overall analysis time while the automated control system manages the complexity of coordinating these preliminary steps with subsequent reactions

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

Enables rapid, automated analysis of nucleic acid sequences from various samples without user intervention, achieving results in under 120 minutes with simultaneous analysis of over 50 target sequences, and is capable of processing samples from diverse sources including blood, saliva, and environmental samples.

Implementation Method 1

microarray detection optics comprising a microarray scanner employing evanescent wave excitation

Methodology Applied
Scientific EffectEvanescent wave:

Implementation Method 2

PCR module configured to perform reverse transcription and PCR in a single reaction

Methodology Applied
Scientific EffectTemperature cycling:

Implementation Method 3

automated hybridization processor configured to provide multiple stringencies via temperature

Methodology Applied
Scientific EffectTemperature control:

Data Source

PatentEP3132073B1Portable nucleic acid analysis system and high-performance microfluidic electroactive polymer actuators
Publication Date: 2021.06.30 SRI INTERNATIONAL
  • EP3132073B1 patent drawingFigure 1
  • EP3132073B1 patent drawingFigure 2A~2B
  • EP3132073B1 patent drawingFigure 2C~2D

AI summary

Devices, systems and methods for the parallel detection of a set of distinct nucleic acid sequences use multiple sequence amplification and simultaneous hybridization readout. An automated nucleic acid analysis system comprises in microfluidic connection sample lysis, purification, PCR and detection modules configured to detect in parallel distinct nucleic acid sequences via multiple sequence amplification and simultaneous microarray hybridization readout. High performance microfluidic electroactive polymer (µEAP) actuators comprising a dead-end fluid chamber in which the floor of the chamber is an electrode covered with an EAP layer of dielectric elastomer are configured for particle sorting.