High-Throughput Fluorescence Imaging with Integrated Sample Heating
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Solution Overview
Problem
Current DNA sequencing and fluorescence imaging techniques face challenges such as time-consuming processes, occasional assay errors, and limited DNA/RNA material availability, which necessitate the need for high-throughput and efficient sample processing methods.
Innovation Solution
A high-throughput fluorescence imaging system with integrated sample heating capability, utilizing an image sensor wafer with multiple sensors and fluidic channels, along with a heating module for temperature control, enables parallel processing and amplification of samples through thermally mediated assays, allowing for efficient DNA sequencing and imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If DNA sequencing is performed sequentially to determine each base, then assay accuracy is maintained, but processing time increases and productivity decreases
Solution Approach 1:
The patent divides the DNA strand into multiple fragments and processes them in parallel across multiple fluidic channels. Each fragment undergoes independent PCR amplification and sequencing, allowing simultaneous determination of multiple bases rather than sequential processing. This segmentation enables high-throughput sequencing while maintaining assay accuracy through independent parallel reactions.
Solution Approach 2:
The imaging system integrates multiple functions into a single platform: PCR amplification, fluorescence imaging, and data analysis. The system can perform different assays (DNA sequencing, genotyping, expression analysis) using the same hardware infrastructure, enabling parallel processing of multiple samples with different assay types while maintaining reliability through standardized protocols.
2Productivity
If multiple samples are processed in parallel to reduce time, then productivity improves, but device complexity increases
Solution Approach 1:
The patent combines PCR amplification, fluorescence imaging, and data analysis capabilities into a single integrated system. Multiple fluidic channels are merged onto one imaging platform, allowing parallel processing of multiple samples simultaneously. The unified system reduces operational complexity compared to using separate instruments for each function while maintaining high throughput.
Solution Approach 2:
The system transitions from sequential one-dimensional processing to parallel two-dimensional processing by arranging multiple fluidic channels in a spatial array on the imaging substrate. This dimensional expansion allows simultaneous interrogation of multiple samples across the field of view, dramatically increasing throughput without proportionally increasing device complexity.
3Quantity of substance
If PCR amplification is used to increase DNA material, then quantity of substance improves, but thermal cycling complexity and time are required
Solution Approach 1:
The system employs isothermal amplification methods that maintain constant temperature rather than requiring thermal cycling. By changing the temperature parameter from variable (cycling between denaturation, annealing, and extension temperatures) to constant (single maintained temperature), the amplification process is simplified and time is reduced while achieving the same DNA quantity increase.
Solution Approach 2:
The patent replaces the mechanical thermal cycling system with a simpler isothermal heating system. Instead of repeatedly heating and cooling the samples through programmed temperature cycles, the system maintains a constant elevated temperature that enables continuous amplification, eliminating the mechanical complexity of thermal cycling while achieving rapid DNA amplification.
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 system facilitates rapid and accurate processing of multiple samples in parallel, reducing operation costs and improving sequencing efficiency while minimizing errors, by modulating temperature and capturing fluorescence images to detect sample components effectively.
Implementation Method 1
a heating module, thermally coupled with the image sensor wafer, for heating the samples
Implementation Method 2
fluorescence imaging is a commonly used technique for detecting components of a biological sample... Sample components of interest are labeled with fluorescent tags that emit fluorescence upon excitation with light
Data Source
AI summary
A method for high-throughput assay processing includes (a) modulating temperature of a plurality of samples disposed in a respective plurality of fluidic channels on an image sensor wafer, including a plurality of image sensors, by heating the image sensor wafer using a heating module thermally coupled with the image sensor wafer, to control reaction dynamics in the samples, and (b) capturing a plurality of fluorescence images of the samples, using the plurality of image sensors, to detect one or more components of the plurality of samples. A method for manufacturing a high-throughput fluorescence imaging system with sample heating capability includes (a) bonding a fluidic wafer, including a plurality of recesses, to an image sensor wafer including a plurality of image sensors, and (b) bonding a heating module, including a heater for generating heat, to the image sensor wafer to thermally couple the heater and the image sensor wafer.