Liquid Metal Thermal Cycler for Rapid PCR

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Solution Overview

Problem

Conventional thermal cyclers face inefficiencies in heat transfer and temperature uniformity, leading to non-specific amplification of nucleic acids and the need for bulky and expensive optical detection systems for real-time monitoring.

Innovation Solution

A thermal cycler design utilizing a liquid composition with high thermal conductivity, such as liquid metal, for rapid and uniform heat transfer, combined with an optical assembly for real-time signal detection from a discrete location within the sample vessel, allowing for precise temperature control and reduced optical system costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of energy

If a conventional metal heating block is used for thermal cycling, then the device structure is simple and robust, but the heat transfer efficiency is poor and temperature uniformity is insufficient

Engineering Contradiction:
Improveheat transfer efficiencyVSAvoiddevice structure
Core Design Contradiction:
Loss of energyVSDevice complexity

Solution Approach 1:

The patent changes the physical state of the heating medium from solid (conventional metal block) to liquid (metal or metal alloy), which fundamentally alters the heat transfer parameters. The liquid composition provides superior thermal conductivity and conformal contact with sample vessels, achieving rapid and uniform heat transfer while maintaining device simplicity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a liquid-based thermal cycling system where the liquid metal or metal alloy composition serves as the heating and cooling medium. This hydraulic approach allows the liquid to flow and conform to the sample vessel geometry, ensuring efficient thermal contact and uniform temperature distribution across all samples

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Speed

If conventional thermal cyclers are used, then the ramp time is slow, but the device structure is simpler

Engineering Contradiction:
Improveramp timeVSAvoiddevice structure
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The patent achieves rapid temperature ramping by changing from solid to liquid heating medium. The liquid metal's high thermal conductivity and ability to conformally contact sample vessels enables extremely fast heat transfer, reducing ramp times significantly while maintaining a relatively simple device structure without complex heating elements

Inventive Principle:
Principle #35Parameter changes

3Device complexity

If conventional thermal cyclers are used, then the optical detection system is bulky and expensive, but the temperature control is adequate

Engineering Contradiction:
Improveoptical detection systemVSAvoidreal-time signal detection
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent extracts the optical detection function from a separate, bulky detection system and integrates it directly into the sample vessel through the liquid metal medium. The liquid metal's optical properties enable signal detection from a discrete location, eliminating the need for complex external optical assemblies while maintaining real-time monitoring capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The liquid metal or metal alloy composition serves multiple functions simultaneously: it acts as the thermal cycling medium, provides optical signal detection, and enables real-time monitoring. This multi-functionality consolidates what would traditionally require separate systems into a single integrated solution

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

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 design enhances the specificity of PCR reactions by achieving rapid and uniform temperature changes, reducing non-specific hybridization, and enabling cost-effective real-time monitoring without the need to remove sample vessels from the heat block.

Implementation Method 1

a heat block comprising a liquid composition... rapid and uniform heat transfer

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 2

at least part of the wall is immersed in a liquid composition that reflects substantially all the signal striking the liquid composition

Methodology Applied
Scientific EffectOptical reflection: Reflection

Data Source

PatentUS9316586B2Apparatus for thermal cycling
Publication Date: 2016.04.19 CALIFORNIA INST OF TECH
  • US9316586B2 patent drawing
  • US9316586B2 patent drawing
  • US9316586B2 patent drawing

AI summary

This invention provides a system for performing PCR, and real time PCR in particular, with great speed and specificity. The system employs a heat block containing a liquid composition to rapidly transfer heat to and from reaction vessels. The system makes use of the reflective properties of the liquid metal to reflect signal from the PCR into the vessel and out the top. In this way, the signal can be measured by an optical assembly in real time without removing the vessels from the heat block.