Microfluidic dPCR System Bubble Removal via Sealing Liquid Flush

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Solution Overview

Problem

Gas bubbles in microfluidic devices during thermocycling cause experimental errors and false assay results due to cross-contamination and optical detection issues, and existing solutions are either insufficient or too complex.

Innovation Solution

A microfluidic system that uses a flow circuit with a pumping means to flush additional sealing liquid through the flow channel, removing existing or emerging gas bubbles and maintaining thermocycling efficiency by using a secondary sealing liquid source and a bubble trap to separate air from the sealing liquid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If thermocycling is performed in a microfluidic device, then DNA amplification is achieved, but gas bubbles form causing cross-contamination and false results

Engineering Contradiction:
Improveassay accuracyVSAvoidgas bubble formation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the harmful gas bubbles to drive the sealing liquid through the flow channel, converting the bubble formation problem into a useful flushing mechanism that clears bubbles from the system and maintains assay reliability

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The sealing liquid acts as an intermediary substance that both seals the reaction areas and serves as a carrier to transport and remove gas bubbles from the flow channel, resolving the contradiction between maintaining seals and removing bubbles

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If sealing liquid is used to prevent bubble formation, then cross-contamination is reduced, but system complexity increases

Engineering Contradiction:
Improveprevention of cross-contaminationVSAvoidsystem structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The sealing liquid performs multiple functions simultaneously: it seals the reaction areas to prevent cross-contamination, flushes gas bubbles through the channel, and maintains thermocycling efficiency, thereby reducing the need for additional separate components

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

Solution Approach 2:

The system uses the presence of gas bubbles themselves to drive the sealing liquid flow that removes the bubbles, creating a self-regulating mechanism that reduces the need for external pumping or control systems

Inventive Principle:
Principle #25Self-service

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

Significantly reduces or eliminates the negative influence of gas bubbles on test results, improving thermocycling efficiency and assay accuracy while simplifying the system structure.

Implementation Method 1

a pumping means connected to the flow circuit and adapted to pump the additional sealing liquid through the flow channel

Methodology Applied
Scientific EffectPumping: Pump

Implementation Method 2

a bubble trap connected to the flow circuit, for separation of air from sealing liquid

Methodology Applied
Scientific EffectGas-liquid separation: Cyclone Separation

Implementation Method 3

a thermal mount receiving the microfluidic device, for providing a thermocycling temperature profile to the array of reaction areas

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Data Source

PatentEP3610947B1Microfluidic system for digital polymerase chain reaction of a biological sample, and respective method
Publication Date: 2021.04.21 F HOFFMANN LA ROCHE & CO AG
  • EP3610947B1 patent drawingFigure 1~2
  • EP3610947B1 patent drawingFigure 3A~3B
  • EP3610947B1 patent drawingFigure 4A~4B

AI summary

A microfluidic system (1; 1') for dPCR of a biological sample and a respective method is provided by the present invention, the system (1; 1') comprising at least one microfluidic device (2) having an inlet (23), an outlet (24), a flow channel (25) connecting the inlet (23) to the outlet (24), and an array of reaction areas (26) in fluidic communication with the flow channel (25), a flow circuit (3) connectable to the microfluidic device (2), for flowing liquid through the flow channel (25) of the microfluidic device (2), a sample liquid source connectable to the microfluidic device (2), for providing the microfluidic device (2) with a sample liquid (27), a primary sealing liquid source connectable to the microfluidic device (2), for providing the microfluidic device (2) with initial sealing liquid (28) for sealing the sample liquid (27) inside the array of reaction areas (26), a secondary sealing liquid source (4) connectable to the microfluidic device (2), for providing the microfluidic device (2) with additional sealing liquid (29), and a pumping means (31) connected to the flow circuit (3) and adapted to pump said additional sealing liquid (29) through the flow channel (25).