Microfluidic Digital PCR Device with Programmable Thermal Zones

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Solution Overview

Problem

Current micro-fluidic PCR devices face limitations in controlling the duration and temperature of PCR cycles, flow speed, and processed volume, with fixed designs that cannot adapt to varying experimental requirements, restricting their versatility in performing both batch and continuous PCR.

Innovation Solution

A micro-fluidic device with a semiconductor substrate, a single heating element connected to a temperature control unit, and an adaptable droplet generator that allows cycling through multiple temperature values and adjusts flow rate, enabling full control over PCR parameters and facilitating both batch and continuous PCR operations without design changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If multiple heating elements with fixed locations are used to heat different zones, then temperature control is achieved, but the compactness of the system is reduced due to required spacing between elements

Engineering Contradiction:
Improvetemperature controlVSAvoidsystem compactness
Core Design Contradiction:
TemperatureVSArea of stationary object

Solution Approach 1:

The single heating element is divided into multiple independently controllable heating zones along the fluidic channel. Each zone can be controlled separately to provide different temperatures at different locations, achieving the function of multiple heating elements while maintaining a compact single-element structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The heating element transitions from a static single-temperature design to a dynamic multi-zone design where different segments can be independently controlled. This allows the system to adapt temperature distribution dynamically along the channel without requiring physical separation of multiple elements.

Inventive Principle:
Principle #15Dynamics

2Productivity

If the flow speed of the fluid sample is modified, then processing time changes, but the duration of all temperature steps is changed proportionally, preventing independent optimization of individual PCR steps

Engineering Contradiction:
Improveprocessing speedVSAvoidtemperature step duration control
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The fluidic channel is divided into multiple heating zones corresponding to different PCR temperature steps. Each zone can independently control the residence time of the fluid at its specific temperature, allowing different duration settings for each PCR step regardless of overall flow speed.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system incorporates sensors and control mechanisms that monitor fluid position and temperature zone activation. This feedback allows the system to adjust heating element activation timing to maintain optimal residence times in each zone even when overall flow speed varies.

Inventive Principle:
Principle #23Feedback

3Ease of manufacture

If a fixed design is used for the micro-fluidic device, then manufacturing is simplified, but the device cannot adapt to varying experimental requirements for different PCR protocols

Engineering Contradiction:
Improvedevice fabricationVSAvoidPCR protocol flexibility
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The micro-fluidic device incorporates a single heating element with multiple independently controllable zones that can be programmed to perform different temperature profiles. This universal design allows the same physical device to execute various PCR protocols (batch and continuous) without hardware changes, achieving versatility through software/control programming.

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

Solution Approach 2:

The device transitions from a static fixed-protocol design to a dynamic programmable design where heating zones can be activated and deactivated in different sequences and durations. This allows the same physical structure to adapt to multiple experimental requirements through dynamic control parameter adjustment.

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 solution provides flexible control over PCR parameters, allowing for precise optimization of PCR cycles, increased versatility, and efficient processing of fluid samples, enabling both batch and continuous PCR operations within the same device setup.

Implementation Method 1

the heating element is a single heating element connected to a temperature control unit configured to cycle the temperature of the complete first micro-fluidic channel through at least two temperature values

Methodology Applied
Scientific EffectThermal cycling:

Implementation Method 2

While propagating through the micro-fluidic channel, DNA present in the fluid sample in the fluidic channel is amplified

Methodology Applied
Scientific EffectPCR amplification:

Implementation Method 3

a droplet generator connected to the inlet of the first micro-fluidic channel for generating droplets and pumping generated droplets at a flow rate into the first micro-fluidic channel

Methodology Applied
Scientific EffectDroplet generation:

Implementation Method 4

the flow rate of the droplet generator is adaptable

Methodology Applied
Scientific EffectFlow rate control:

Data Source

PatentUS11266990B2Device and method for performing digital PCR
Publication Date: 2022.03.08 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • US11266990B2 patent drawing
  • US11266990B2 patent drawing
  • US11266990B2 patent drawing

AI summary

A micro-fluidic device 100 for performing digital PCR is presented. The device comprises: a semiconductor substrate; a first micro-fluidic channel 104, comprising an inlet 102 and an outlet 103, embedded in the semiconductor substrate; a heating element 101 thermally coupled to the first micro-fluidic channel 104; a droplet generator 107 connected to the inlet 102 of the first micro-fluidic channel 104 for generating droplets and pumping generated droplets at a flow rate into the first micro-fluidic channel 104; characterized in that: the heating element 101 is a single heating element connected to a temperature control unit 111 configured to cycle the temperature of the complete first micro-fluidic channel 104 through at least two temperature values; and wherein the flow rate of the droplet generator 107 is adaptable. Further, a method to perform digital PCR is presented using the micro-fluidic device 100.