Microfluidic Rapid Thermal Cycling Device for Nucleic Acid Amplification

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Solution Overview

Problem

Current nucleic acid amplification techniques are cumbersome and costly, requiring lengthy thermal cycles that can take over an hour and are not suitable for rapid or point-of-care applications due to their size and complexity.

Innovation Solution

A rapid thermal cycling device with a microfluidic reaction chamber, dry reagent, and a high thermal conductivity heating element that allows for rapid heating and cooling of nucleic acid samples, enabling efficient nucleic acid amplification within a compact and cost-effective system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional thermal cycling equipment is used for nucleic acid amplification, then amplification can be achieved, but the process takes over an hour and the equipment is costly and cumbersome

Engineering Contradiction:
Improveamplification speedVSAvoidequipment complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The device segments the thermal cycling function into a microfluidic reaction chamber with integrated heating and cooling zones, allowing independent control of temperature zones within the same device. This segmentation enables rapid thermal cycling without requiring large, complex external equipment.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from conventional bulk thermal cycling to microfluidic dimension, where the reaction occurs in a miniaturized chamber with controlled fluid flow. This dimensional change enables faster heat transfer and reduced thermal mass, achieving rapid amplification in minutes rather than hours.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Loss of time

If thermal cycling time is reduced for rapid amplification, then point-of-care applications become feasible, but thermal control precision becomes more challenging

Engineering Contradiction:
Improveamplification timeVSAvoidthermal control precision
Core Design Contradiction:
Loss of timeVSManufacturing precision

Solution Approach 1:

The device changes the thermal parameters by using a thermally diffusive substrate material with high thermal conductivity, enabling rapid heat distribution throughout the microfluidic chamber. This parameter change allows fast thermal cycling while maintaining uniform temperature control across the reaction volume.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The heating element is immediately adjacent to and thermally coupled with the microfluidic reaction chamber, creating a direct thermal feedback pathway. This immediate thermal coupling enables precise control of temperature changes during rapid cycling, maintaining accuracy despite the reduced time scale.

Inventive Principle:
Principle #23Feedback

3Volume of moving object

If a compact device is designed for rapid thermal cycling, then portability is improved, but heat dissipation and thermal management become more difficult

Engineering Contradiction:
Improvedevice sizeVSAvoidheat dissipation efficiency
Core Design Contradiction:
Volume of moving objectVSLoss of energy

Solution Approach 1:

The device utilizes the phase transition properties of the fluid sample within the microfluidic chamber, where rapid heating and cooling cycles induce controlled phase changes that facilitate nucleic acid amplification. The small thermal mass of the microfluidic chamber enables efficient heat dissipation during cooling phases despite the compact size.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The thermally diffusive substrate acts as an intermediary between the heating element and the fluid sample, efficiently distributing thermal energy throughout the reaction chamber. This intermediary material enables effective heat management in the compact device by preventing localized overheating and facilitating uniform thermal cycling.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 nucleic acid amplification, reducing the amplification time to minutes and making it suitable for point-of-care diagnostics and forensic testing by utilizing a microfluidic reaction chamber with a thermally diffusive substrate and a heating element that can heat fluids at rates of up to 50,000,000 °C/s.

Implementation Method 1

a heating element immediately adjacent and thermally coupled to the microfluidic reaction chamber to heat a fluid when introduced therein

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 2

The substrate includes a thermal diffusing layer having a thermal conductivity that ranges from 20 W/m/K to 2,000 W/m/K as measured at PCR temperatures

Methodology Applied
Scientific EffectThermal diffusion: Conduction (thermal)

Data Source

PatentEP3824297B1Rapid thermal cycling devices
Publication Date: 2024.02.21 HEWLETT PACKARD DEVELOPMENT COMPANY LP
  • EP3824297B1 patent drawingFigure 1A~2
  • EP3824297B1 patent drawingFigure 3~4
  • EP3824297B1 patent drawingFigure 5

AI summary

A rapid thermal cycling device can include a microfluidic reaction chamber, a dry reagent, and a heating element. The microfluidic reaction chamber can be defined between a substrate and a cover having an average space therebetween from 4 µm to 150 µm. The dry reagent can be positioned within the microfluidic reaction chamber. The heating element can be thermally coupled to the microfluidic reaction chamber to heat a fluid when introduced therein.