Reciprocal-Flow Nucleic Acid Amplification Device for Rapid PCR

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Solution Overview

Problem

Current PCR and real-time PCR methods are slow and cumbersome, making them unsuitable for rapid, on-site genetic testing, particularly in clinical settings or for infectious disease outbreaks, due to their large size, high cost, and difficulty in automation, especially when detecting RNA viruses or performing multiplex reactions.

Innovation Solution

A reciprocal-flow-type nucleic acid amplification device with two temperature zones and microchannels, utilizing liquid delivery mechanisms like fans to facilitate rapid thermal cycling and fluorescence measurement, enabling high-speed, real-time PCR with a compact and portable design that can perform PCR, RT-PCR, and multiplex reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional PCR methods are used with thermal cycling, then nucleic acid amplification can be achieved, but the process is slow and takes 1-2 hours or more

Engineering Contradiction:
Improveamplification speedVSAvoidtesting time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent replaces the conventional thermal cycling mechanical system with a pressure-driven flow system. By applying pressure to drive sample solution through microchannels at controlled flow rates, the system eliminates the need for repeated heating and cooling cycles, achieving amplification in under 10 minutes instead of 1-2 hours.

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

Solution Approach 2:

The invention uses pressure control mechanisms to regulate sample solution flow through microchannels. By precisely controlling the pressure applied to the sample, the system maintains optimal flow rates for rapid amplification while enabling simple on/off control of the pressure source for efficient operation.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Productivity

If general-purpose thermal cycle devices are used, then PCR can be performed, but the devices are large and not suitable for portable use

Engineering Contradiction:
Improveamplification capabilityVSAvoiddevice size
Core Design Contradiction:
ProductivityVSWeight of moving object

Solution Approach 1:

The patent divides the amplification system into separate functional modules: pressure control mechanism, microchannel array, and detection system. This segmentation allows each component to be miniaturized and optimized independently, resulting in a compact portable device that fits in a small footprint while maintaining full amplification capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from the conventional three-dimensional thermal block design to a two-dimensional microchannel planar structure. By arranging multiple microchannels in parallel on a flat substrate, the system achieves high throughput amplification in a thin, portable format that is suitable for field deployment.

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

3Productivity

If conventional PCR devices are used, then amplification can be achieved, but the devices are expensive and complex

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

Solution Approach 1:

The patent employs passive flow control mechanisms where the microchannel geometry and pressure gradient automatically regulate sample flow without requiring complex active control systems. The system self-regulates flow rates through pressure equalization and gravity-assisted drainage, eliminating the need for expensive pumps, valves, and control electronics.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The microchannel array is designed to perform multiple functions: sample loading, pressure application, thermal exchange, and waste removal. By integrating these functions into a single unified structure, the device eliminates the need for separate components for each operation, reducing overall system complexity and cost.

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

4Ease of operation

If pressure is applied to drive sample solution, then flow control is achieved, but pressure equalization and waste removal become challenging

Engineering Contradiction:
Improveflow controlVSAvoidpressure management
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent implements periodic pressure application cycles: pressure is applied to drive sample through microchannels during the amplification phase, then pressure is released to equalize and allow waste removal. This rhythmic on/off pressure control simplifies the management of pressure equalization and waste evacuation without requiring complex continuous control systems.

Inventive Principle:
Principle #19Periodic action

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 achieves rapid and accurate nucleic acid amplification, allowing for quick on-site genetic testing with reduced costs and complexity, capable of performing real-time PCR in under 10 minutes, with precise position control and simultaneous fluorescence measurement, enhancing the detection of infectious diseases.

Implementation Method 1

liquid delivery mechanisms by which a plug sample solution is reciprocated between precise positions in the temperature zones through the microchannel

Methodology Applied
Scientific EffectPressure differential: Pressure Gradient

Implementation Method 2

measuring fluorescence intensity for each thermal cycle

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11781181B2Nucleic acid amplification device, nucleic acid amplification method, and chip for nucleic acid amplification
Publication Date: 2023.10.10 KYORIN PHARMACEUTICAL CO LTD
  • US11781181B2 patent drawing
  • US11781181B2 patent drawing
  • US11781181B2 patent drawing

AI summary

The present invention provides a reciprocal-flow-type nucleic acid amplification device comprising:heaters capable of forming a denaturation temperature zone and an extension/annealing temperature zone;a fluorescence detector capable of detecting movement of a sample solution between the two temperature zones;a pair of liquid delivery mechanisms that allow the sample solution to move between the two temperature zones and that are configured to be open to atmospheric pressure when liquid delivery stops; a substrate on which the chip for nucleic acid amplification according to claim 2 can be placed; and a control mechanism that controls driving of each liquid delivery mechanism by receiving an electrical signal from the fluorescence detector relating to movement of the sample solution from the control mechanism; the device being capable of performing real-time PCR by measuring fluorescence intensity for each thermal cycle.