Metallic Sample Holder for Rapid Thermal Cycling in Nucleic Acid Detection

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Solution Overview

Problem

Conventional sample holders for nucleic acid amplification tests, such as PCR, face challenges in achieving precise temperature control and rapid thermal cycling due to their large thermal mass and inefficient heat transfer, leading to potential side reactions and inaccurate temperature monitoring.

Innovation Solution

A metallic sample holder with an array of wells, where each well is thermally connected to ensure uniform temperature across sectors, allowing for efficient heating and cooling, and is designed for automated sample preparation with specific patterns for nucleic acid detection, including sectors for different test kits and primers for simultaneous detection of multiple nucleic acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional thermal blocks with large thermal mass are used, then temperature stability is improved, but thermal cycling speed deteriorates

Engineering Contradiction:
Improvetemperature stabilityVSAvoidthermal cycling speed
Core Design Contradiction:
Stability of the object's compositionVSSpeed

Solution Approach 1:

The invention divides the sample holder into multiple independent wells, each capable of holding small sample volumes. This segmentation allows each well to be thermally processed independently and rapidly, eliminating the need to heat/cool large thermal masses while maintaining temperature stability through precise control of individual well temperatures during thermal cycling

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the sample volume parameter from conventional large volumes (in tubes or plates) to micro-volumes (nanoliter scale). This parameter change reduces the thermal mass significantly, enabling fast thermal cycling speeds while maintaining adequate temperature stability for PCR reactions through the small volume's rapid thermal response

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If conventional sample holders with tubes or plates are used, then sample capacity is improved, but temperature control precision deteriorates

Engineering Contradiction:
Improvesample capacityVSAvoidtemperature control precision
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The sample holder is segmented into multiple discrete wells, each designed to hold a specific small sample volume. This segmentation enables precise temperature control for each well independently, as the small thermal mass of each well responds quickly and uniformly to heating/cooling, eliminating temperature gradients that plague conventional large-volume holders

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention replaces conventional mechanical thermal blocks with Peltier elements that provide direct, precise thermal control at the well level. This substitution enables accurate temperature monitoring and control for each sample well, achieving the temperature precision needed for NAAT while maintaining the capacity to process multiple samples simultaneously

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Power

If Peltier elements with large thermal mass are used, then heating capacity is improved, but cooling speed deteriorates

Engineering Contradiction:
Improveheating capacityVSAvoidcooling speed
Core Design Contradiction:
PowerVSSpeed

Solution Approach 1:

The invention changes the sample volume parameter to nanoliter scale, which dramatically reduces the thermal mass that needs to be heated or cooled. This parameter change allows Peltier elements to achieve both high heating capacity and fast cooling speed, as the small sample volumes respond rapidly to thermal input changes without requiring large thermal masses

Inventive Principle:
Principle #35Parameter changes

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 metallic sample holder enables precise and rapid thermal cycling, preventing side reactions and improving the accuracy of nucleic acid detection by maintaining uniform temperature across sample volumes, thus enhancing the efficiency of nucleic acid amplification tests like PCR.

Implementation Method 1

A metallic sample holder with an array of wells, where each well is thermally connected to ensure uniform temperature across sectors

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 2

One or more Peltier units are used to heat or cool the thermal block that has a thermal mass at least one hundred times larger than the thermal mass of sample volumes captured within the tubes or plates

Methodology Applied
Scientific EffectPeltier effect: Peltier Effect

Data Source

PatentUS20230332257A1A metallic sample holder, a probe for performng detection reactions, and apparatus for receiving the sample holder
Publication Date: 2023.10.19 ETH ZURICH
  • US20230332257A1 patent drawing
  • US20230332257A1 patent drawing
  • US20230332257A1 patent drawing

AI summary

A metallic sample holder includes an array of wells, wherein each well of the array is adapted to capture a sample volume. A first sector of the array comprises wells that are loaded with a first reagent of a first dried or freeze-dried nucleic acid amplification test reagent. A second sector of the array comprises wells that are loaded with a second reagent of a second dried or freeze-dried nucleic acid amplification test reagent.