Parallel Nucleic Acid Sequencing With Concurrent Chemistry and Imaging
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Solution Overview
Problem
Existing genetic sequencing techniques are highly time-intensive and costly, limiting the speed and reliability of genomic information acquisition.
Innovation Solution
A method and system for nucleic acid sequencing that includes automated nucleic acid sequencing operations, quality evaluation, and adaptive control of sequencing procedures based on detected parameters, using systems with integrated fluidics, imaging, and quality evaluation circuitry to enhance throughput and reduce costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If existing genetic sequencing techniques are used, then sequencing can be performed, but the process is highly time-intensive and costly
Solution Approach 1:
The system segments the sequencing process into multiple parallel flow cells, each capable of independent sequencing reactions. Multiple flow cells can be imaged simultaneously by the imaging system, enabling parallel processing of multiple samples or multiple sequencing cycles, thereby dramatically increasing throughput while reducing overall sequencing time
Solution Approach 2:
The system performs preliminary actions by pre-positioning multiple flow cells in the imaging system and pre-loading reagents into the fluidics system before sequencing begins. The imaging system is pre-configured with multiple cameras positioned to capture images of all flow cells simultaneously, eliminating setup time during the sequencing process and maximizing productivity
Solution Approach 3:
The system changes the parameter of parallelism by implementing multiple flow cells that can be imaged simultaneously rather than sequentially. The fluidics system delivers reagents to multiple flow cells in parallel, and the imaging system captures data from all flow cells at the same time, transforming the sequencing process from a sequential operation to a parallel one, thereby increasing throughput and reducing time
2Productivity
If existing genetic sequencing techniques are used, then sequencing can be performed, but the process is highly costly
Solution Approach 1:
The fluidics system is designed as a universal platform that can deliver multiple different reagents (nucleotides, enzymes, buffers) to multiple flow cells using a shared set of dispensing mechanisms. The imaging system serves multiple flow cells simultaneously with a single multi-camera setup. This multi-functionality reduces the need for duplicate equipment for each flow cell, thereby reducing overall reagent consumption and system cost while maintaining high throughput
Solution Approach 2:
The system merges multiple sequencing operations into a single integrated platform where multiple flow cells share common reagent delivery and imaging resources. Instead of having separate systems for each flow cell, the fluidics system combines reagent delivery to multiple cells, and the imaging system combines multiple cameras into a single integrated imaging station. This consolidation reduces redundant reagent consumption and lowers overall system cost while increasing productivity
3Productivity
If automated sequencing operations are implemented, then throughput increases, but system complexity increases
Solution Approach 1:
The system implements feedback control where the imaging system continuously monitors the sequencing reactions in real-time across multiple flow cells. The captured images are analyzed to determine reaction progress, and this information feeds back to the fluidics system to control reagent delivery timing and concentration. This automated feedback loop enables high throughput sequencing while managing system complexity through intelligent control rather than purely mechanical complexity
Solution Approach 2:
The system replaces complex mechanical manipulation with optical detection and computational analysis. Instead of mechanically moving samples through multiple processing stages, the system uses a stationary multi-flow-cell configuration with optical imaging to monitor and control the sequencing reactions. The fluidics system uses programmed reagent delivery rather than complex mechanical assembly/disassembly, reducing mechanical complexity while maintaining high throughput through automated optical monitoring and control
Data Source
AI summary
A system for sequencing nucleic acid comprising a plurality of stations and a system control. The system control configured to direct the first substrate to progress and retrogress between the first processing station and the imaging station, direct the second substrate to progress and retrogress between the second processing station and the imaging station, and direct a chemistry cycle of a first sequencing procedure to occur within one of the first processing station or the second processing station while an imaging cycle of a second sequencing procedure occurs within the imaging station.