Microfluorometer Fluidic System for High-Throughput Sequencing
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Solution Overview
Problem
Current nucleic acid sequencing technologies are hindered by high costs and slow throughput, making them impractical for large-scale genetic correlation studies and clinical applications, where rapid and inexpensive sequencing is necessary to determine individual genomic sequences and correlate them with phenotypes.
Innovation Solution
A detection apparatus comprising a microfluorometer with a fluidic system that delivers reagents from a reagent cartridge to a flow cell, enabling wide-field image detection and sequencing-by-synthesis protocols, which includes a manifold body with fluidic channels, reagent sippers, and a valve for efficient reagent management and imaging of nucleic acid features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional sequencing techniques are used, then sequencing accuracy is maintained, but sequencing cost is high and throughput is slow
Solution Approach 1:
The system divides the sequencing process into discrete cycles, each handling a specific nucleotide type (A, C, G, T). The flow cell is segmented into multiple regions that can be independently imaged, and reagents are delivered through separate channels for each nucleotide type. This segmentation enables parallel processing and increases throughput while maintaining manageable system complexity.
Solution Approach 2:
The sequencing process uses periodic action through cyclic repetition of four distinct steps (first, second, third, and fourth cycles) where each cycle introduces a specific nucleotide type. This periodic structure allows systematic data collection across all nucleotide positions, enabling high-throughput sequencing while organizing complexity into repeatable, manageable units.
2Loss of time
If conventional sequencing techniques are used, then comprehensive genomic data is obtained, but time consumption is excessive
Solution Approach 1:
The system maintains continuous useful action by implementing automated reagent delivery and continuous imaging throughout the sequencing process. The fluidic system continuously supplies reagents without interruption, and the imaging system continuously captures fluorescence signals across all flow cell regions. This continuity eliminates idle time between operations while maintaining accurate base calling through consistent signal detection.
Solution Approach 2:
The system performs preliminary actions by pre-loading all necessary reagents into the flow cell before the actual sequencing begins. The priming process prepares the flow cell with appropriate buffers and reagents in advance, and the system pre-positions imaging and fluidic components for immediate operation. This preliminary preparation eliminates setup time during the actual sequencing run while ensuring all conditions are optimized for accurate measurement.
3Productivity
If high-throughput sequencing is implemented, then cost per sequence is reduced, but system complexity increases
Solution Approach 1:
The system implements universality through multi-functional components that perform multiple operations. The flow cell serves both as a reaction chamber and an imaging substrate. The fluidic system handles both reagent delivery and waste removal. The imaging system captures data across multiple flow cell regions simultaneously. This multi-functionality increases throughput while reducing the number of separate components needed, thereby managing operational complexity.
Solution Approach 2:
The system incorporates self-service features through automated reagent delivery and imaging acquisition. The fluidic system automatically supplies reagents based on the sequencing cycle without manual intervention. The imaging system automatically captures and processes images across all flow cell regions. This automation reduces operational complexity by eliminating manual steps while maintaining high throughput through continuous automated operation.
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 solution reduces sequencing costs and increases throughput, allowing for rapid and accurate determination of genomic sequences, facilitating clinical relevance and accessibility in genetic correlation studies and patient treatment decisions.
Implementation Method 1
a microfluorometer having an objective, an excitation radiation source, and a detector. The microfluorometer is configured for wide-field image detection... The objective is configured to direct excitation radiation from the radiation source to the flow cell and to direct emission from the flow cell to the detector.
Data Source
AI summary
Detection apparatus includes a microfluorometer having an objective, an excitation radiation source, and a detector. The detection apparatus also includes a fluidic system for delivering reagents from a reagent cartridge to a flow cell. The fluidic system includes a manifold body having a plurality of fluidic channels configured for fluid communication between the reagent cartridge and the flow cell. The fluidic system also includes a plurality of reagent sippers. The fluidic system also includes a valve configured to mediate fluid between reagent reservoirs and the flow cell. The detection apparatus also includes a flow cell latch clamp module having a clamp cover for holding the flow cell. The objective is configured to direct excitation radiation from the radiation source to the flow cell and to direct emission from the flow cell to the detector. The microfluorometer is movable to acquire wide-field images of different areas of the flow cell.