Systems and methods using external heater systems in microfluidic devices

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Solution Overview

Problem

Current microfluidic heating systems face challenges in achieving uniform temperature control, leading to non-reproducible melt curves and limited throughput in nucleic acid analysis, particularly in PCR and high-resolution melt analysis, due to non-uniform heating and large heater blocks.

Innovation Solution

The implementation of a microfluidic device with thin-film resistive temperature detectors (RTDs) and a heat spreader configured for symmetric heating, using materials like copper, aluminum, and anisotropic conductive materials to ensure uniform temperature distribution across microchannels, and the use of a comprehensive heating system with a heat spreader and interconnection materials to promote thermal uniformity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If conventional heater blocks are used for heating microfluidic devices, then heating capability is provided, but temperature uniformity across microchannels deteriorates

Engineering Contradiction:
Improvetemperature uniformityVSAvoidheating system structure
Core Design Contradiction:
TemperatureVSDevice complexity

Solution Approach 1:

The heater block is segmented into multiple independent heating zones, each with its own heater element positioned adjacent to specific microchannels. This allows independent temperature control for different channel groups, ensuring uniform heating across all channels while maintaining a relatively simple overall structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the heater block are designed with different heating characteristics to match the specific thermal requirements of adjacent microchannels. Each heating zone is optimized locally to provide the appropriate temperature profile for its associated channels, achieving global temperature uniformity through local optimization.

Inventive Principle:
Principle #3Local quality

2Reliability

If heater blocks are used for thermal cycling, then PCR reactions can be performed, but melt curve reproducibility deteriorates due to non-uniform heating

Engineering Contradiction:
Improvemelt curve reproducibilityVSAvoidtemperature control precision
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

Temperature sensors are positioned adjacent to the microchannels to provide real-time feedback on the actual temperature experienced by the samples. This feedback is used to dynamically adjust the heating power of each heating zone, compensating for thermal variations and ensuring reproducible melt curves. The system continuously monitors and corrects temperature deviations during PCR and melt analysis.

Inventive Principle:
Principle #23Feedback

3Productivity

If large heater blocks are used, then heating capacity is sufficient, but processing time increases and throughput is limited

Engineering Contradiction:
Improveprocessing throughputVSAvoidthermal cycling time
Core Design Contradiction:
ProductivityVSDuration of action of moving object

Solution Approach 1:

The heater block is divided into multiple independent heating zones that can be controlled separately. This allows parallel thermal processing of multiple microchannel groups simultaneously, reducing the overall thermal cycling time while maintaining sufficient heating capacity for all channels.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The heating system transitions from static, uniform heating to dynamic, zone-specific heating control. Each heating zone can independently adjust its power output based on real-time temperature feedback, enabling faster thermal response times and reduced processing cycles while maintaining temperature uniformity across all microchannels.

Inventive Principle:
Principle #15Dynamics

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

This approach enables highly reproducible melt curves and improved genotyping by ensuring uniform temperature profiles across all microchannels, reducing processing time and increasing throughput in nucleic acid analysis.

Implementation Method 1

thin-film resistive temperature detectors (RTDs)

Methodology Applied
Scientific EffectResistive temperature detection: Electrical Resistance

Implementation Method 2

heat spreader configured for symmetric heating, using materials like copper, aluminum, and anisotropic conductive materials to ensure uniform temperature distribution

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Data Source

PatentEP2710859B1Systems and methods using external heater systems in microfluidic devices
Publication Date: 2019.09.04 CANON US LIFE SCIENCES INC
  • EP2710859B1 patent drawingFigure 1
  • EP2710859B1 patent drawingFigure 2
  • EP2710859B1 patent drawingFigure 3

AI summary

The present invention relates to methods and systems that result in high quality, reproducible, thermal melt analysis on a microfluidic platform. The present invention relates to methods and systems using thermal systems including heat spreading devices, including interconnection methods and materials developed to connect heat spreaders to microfluidic devices. The present invention also relates to methods and systems for controlling, measuring, and calibrating the thermal systems of the present invention.