Digital PCR Thermocycling Assembly for Fast Uniform Melt Analysis
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Solution Overview
Problem
Current workflows for analyzing bacterial infections require multiple days, leading to delayed treatment and potential drug resistance, necessitating a quicker system for antimicrobial susceptibility testing.
Innovation Solution
A thermooptical system with a thermocycling assembly and optical imaging system for rapid thermocycling and high temperature uniformity, enabling 8°C/sec ramp rates and uniform temperature control across a digital PCR cartridge for digital melt analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional thermocycling systems are used for digital PCR, then temperature control is achieved, but the processing time is too long (multiple days)
Solution Approach 1:
The system divides the thermal control into multiple independent heating zones along the thermal plate, allowing different regions to be heated simultaneously at different rates. This segmentation enables parallel processing of multiple samples at different temperature stages, dramatically reducing total processing time from days to minutes
Solution Approach 2:
The patent employs a liquid cooling system with channels that circulate temperature-controlled fluid beneath the thermal plate. This hydraulic approach enables rapid heat dissipation and precise temperature cycling, achieving the required 8°C/sec ramp rates and reducing processing time while maintaining temperature uniformity across all chambers
2Productivity
If rapid thermocycling is implemented, then processing time is reduced, but temperature uniformity across the thermal plate deteriorates
Solution Approach 1:
The thermal plate is divided into multiple heating zones with independent temperature control. During rapid heating, different zones can be activated sequentially or simultaneously at different power levels to achieve the target ramp rate while distributing thermal load evenly across the plate surface, preventing hot spots and maintaining uniformity
Solution Approach 2:
The liquid cooling system uses strategically positioned cooling channels beneath the thermal plate that provide active thermal management during rapid heating cycles. The circulating fluid absorbs excess heat from high-power heating zones and redistributes thermal energy, enabling 8°C/sec ramp rates while maintaining temperature uniformity across the entire plate surface
3Measurement precision
If conventional processing workflows are used, then accuracy is maintained, but treatment delay increases leading to drug resistance
Solution Approach 1:
The system integrates multiple detection functions (fluorescence imaging, temperature monitoring, melt analysis) into a single automated platform that processes all measurements during the rapid thermocycling run. This eliminates sequential processing steps and external culture requirements, achieving both speed (10-60 minutes) and accuracy through simultaneous multi-parameter measurement
Solution Approach 2:
The patent combines PCR amplification, real-time fluorescence detection, and melt analysis into a single integrated system. All measurements are captured during the rapid thermocycling process itself, eliminating the need for separate culture steps or additional instrumentation. This merging of functions achieves rapid processing (10-60 minutes) without compromising identification accuracy
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
Facilitates rapid PCR processing (10-60 minutes) and accurate digital melt analysis, allowing for quick identification of pathogen biomarkers and antimicrobial susceptibility testing without culture.
Implementation Method 1
thermal electric cooling elements disposed between the flat thermal plate and the heat sink, wherein the thermal electric cooling elements are configured to regulate a temperature of the flat thermal plate during the thermocycling
Implementation Method 2
a liquid cooling system coupled to the heat sink and configured to flow a liquid through the internal liquid conduit to facilitate rapid cooling of the flat thermal plate during thermocycling
Implementation Method 3
a flat thermal plate having a first side configured to contact and to thermally interface with a flat digital PCR cartridge including thousands of chambers for samples
Data Source
AI summary
A system includes a thermocycling assembly configured to perform thermocycling for a digital polymerase chain reaction (PCR). The thermocycling assembly includes a flat thermal plate having a first side configured to contact and to thermally interface with a flat digital PCR cartridge including thousands of chambers for samples. The thermocycling assembly also includes a heat sink disposed beneath the flat thermal plate including an internal liquid conduit. The thermocycling assembly further includes thermal electric cooling elements disposed between the flat thermal plate and the heat sink, wherein the thermal electric cooling elements are configured to regulate a temperature of the flat thermal plate during the thermocycling. The thermocycling assembly even further includes a liquid cooling system coupled to the heat sink and configured to flow a liquid through the internal liquid conduit to facilitate rapid cooling of the flat thermal plate during thermocycling.