Miniaturized PCR Chip with Segmented Thermal Control

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Solution Overview

Problem

Conventional thermal cyclers for PCR are expensive due to their large thermal mass and low heat conductivity, making them inefficient for high-throughput nucleic acid amplification, and they lack automated sealing and real-time monitoring capabilities.

Innovation Solution

Miniaturized chips with arrays of thermo-controllable units and micro wells, sealed using radiation-curable adhesives, integrated with indium tin oxide heaters and optical systems for precise temperature control and real-time monitoring of chemical reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If conventional thermal cyclers with metal heating blocks and cooling reservoirs are used, then temperature control for PCR is achieved, but the large thermal mass and low heat conductivity result in high electrical power consumption and reduced productivity

Engineering Contradiction:
Improvetemperature controlVSAvoidhigh-throughput amplification efficiency
Core Design Contradiction:
TemperatureVSProductivity

Solution Approach 1:

The invention divides the thermal cycler into multiple independent heating blocks, each capable of processing separate samples simultaneously. This segmentation allows parallel processing of multiple reactions, thereby increasing throughput while maintaining precise temperature control for each individual block.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces vertical stacking of multiple heating blocks in the z-dimension, allowing simultaneous processing of numerous samples in a compact footprint. This dimensional approach increases productivity without proportionally increasing the thermal mass of individual heating elements.

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

2Temperature

If conventional thermal cyclers with metal heating blocks are used, then temperature control is achieved, but the large thermal mass requires high level of electrical power

Engineering Contradiction:
Improvetemperature controlVSAvoidelectrical power consumption
Core Design Contradiction:
TemperatureVSUse of energy by stationary object

Solution Approach 1:

By dividing the heating system into multiple smaller, independent heating blocks, each block has reduced thermal mass compared to a single large block. This allows each segment to heat and cool more efficiently with lower power consumption while maintaining the required temperature control precision for PCR reactions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each heating block is designed with localized thermal optimization, using materials and geometries tailored to minimize thermal mass while maintaining effective temperature control. This local optimization reduces the power required for each individual block compared to a monolithic design.

Inventive Principle:
Principle #3Local quality

3Volume of stationary object

If channel- or chamber-based miniaturized devices are used, then thermal mass is reduced and reaction volume is minimized, but the channels or chambers are not amenable to automated sealing that prevents evaporation and cross contamination

Engineering Contradiction:
Improvereaction volumeVSAvoidautomated sealing capability
Core Design Contradiction:
Volume of stationary objectVSEase of manufacture

Solution Approach 1:

The device uses discrete micro-wells as separate reaction chambers, each capable of being independently sealed. This segmented architecture allows automated sealing mechanisms to access and seal each well individually, preventing evaporation and cross-contamination while maintaining miniaturization benefits.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces a sealing mechanism that acts as an intermediary between the micro-well array and the environment. This sealing system can be automatically applied to each well after sample loading, providing evaporation prevention and cross-contamination protection without requiring complex integrated seals in the chip fabrication.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Productivity

If conventional thermal cyclers are used, then PCR reactions can be performed, but real-time monitoring of the amplification reaction is not available

Engineering Contradiction:
Improveamplification capabilityVSAvoidreal-time monitoring capability
Core Design Contradiction:
ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The heating blocks are designed to serve multiple functions: thermal processing of samples and simultaneous optical detection of amplification reactions. Integrated optical paths allow the same device structure to perform both heating and monitoring, enabling real-time PCR without adding separate monitoring equipment.

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

Solution Approach 2:

The system incorporates real-time optical detection that provides feedback on the progress of amplification reactions. This feedback mechanism allows monitoring of reaction kinetics and endpoint detection, enabling quantitative analysis of PCR amplification as it occurs rather than requiring post-reaction analysis.

Inventive Principle:
Principle #23Feedback

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

Enables high-throughput, cost-effective nucleic acid amplification with precise temperature control and real-time monitoring, reducing thermal cycling time and preventing evaporation and cross-contamination.

Implementation Method 1

a heating element in thermal contact with the micro well

Methodology Applied
Scientific EffectJoule heating: Joule Heating

Implementation Method 2

sealed by (a) applying a radiation-curable adhesive along peripheral dimensions defining an open surface of the micro well; (b) placing a cover to encompass the peripheral dimensions that define the open surface of the micro well; and (c) exposing the micro well to a radiation bean to effect the sealing

Methodology Applied
Scientific EffectPhotopolymerisation: Photopolymerisation

Data Source

PatentUS7622296B2Apparatus and method for multiplex analysis
Publication Date: 2009.11.24 TAKARA BIO USA INC
  • US7622296B2 patent drawing
  • US7622296B2 patent drawing
  • US7622296B2 patent drawing

AI summary

The present invention provides miniaturized instruments for conducting chemical reactions where control of the reaction temperature is desired or required. Specifically, this invention provides chips and optical systems for performing and monitoring temperature-dependent chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost amplification of nucleic acids.