Multiple Primer Sequencing for Data Rate and Density
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Solution Overview
Problem
Current Next-Generation Sequencing technologies, such as sequencing by synthesis (SBS), face limitations in data rate and density, particularly when dealing with large genomes, necessitating further improvements to efficiently process and analyze genetic information.
Innovation Solution
A method involving multiple primers bound at different positions on the same nucleic acid strand, allowing for simultaneous extension reads and the use of uniquely labeled nucleotide analogues to enhance data density and rate, utilizing enzymes like polymerase or ligase for sequencing by synthesis or ligation, and processing signal data to allocate bases to extension reads.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If multiple primers are used to sequence the same nucleic acid strand, then data rate and density are significantly increased, but the complexity of the sequencing system increases
Solution Approach 1:
The sequencing process is segmented by using multiple primers that bind at different positions along the nucleic acid strand. Each primer initiates a separate extension read, allowing parallel sequencing of multiple regions simultaneously. This segmentation enables the system to process larger genomes faster by dividing the sequencing task into concurrent operations rather than sequential ones.
Solution Approach 2:
Multiple extension reads generated from different primers binding sites are merged and integrated into a single comprehensive sequence determination. The system combines data from all extension reads, allocating bases to the correct read based on their origin, thereby achieving high data rate while maintaining sequence accuracy through consolidation of parallel results.
2Productivity
If multiple primers bound at different positions are used for simultaneous extension reads, then data density is increased, but the difficulty of detecting and measuring signals increases
Solution Approach 1:
The sequencing reads are segmented by assigning each extension read to a specific primer binding site. This segmentation allows the system to track and measure signals from different locations independently, then allocate them to the correct read during data processing. The segmentation approach maintains signal detection clarity even when multiple primers are used simultaneously.
Solution Approach 2:
The system uses the primer binding positions as intermediary markers to distinguish and track signals from different extension reads. By anchoring each read to its originating primer site, the system can reliably measure and detect signals without confusion, even when multiple extension reactions occur simultaneously in the same sequencing well.
3Speed
If multiple extension reads are performed simultaneously, then sequencing speed increases, but the complexity of processing and allocating bases to correct reads increases
Solution Approach 1:
The system performs preliminary action by pre-establishing the binding positions and identities of multiple primers before sequencing begins. This preliminary configuration allows the system to automatically allocate bases to the correct extension reads during data processing, as the primer-mapping relationships are already defined. This pre-prepared framework simplifies the complex task of sorting and assigning parallel sequencing data.
Solution Approach 2:
The system uses feedback mechanisms to track which primer generated which extension read and to verify the accuracy of base allocation. By monitoring the sequencing process and comparing results against expected patterns from known primer binding sites, the system can correct errors and ensure accurate base assignment, thereby managing processing complexity while maintaining high sequencing speed.
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 approach significantly increases the data rate and density of sequencing, enabling more efficient and accurate determination of nucleic acid sequences, particularly for large genomes, by allowing multiple base calls at each location and simultaneous identification of nucleotide bases.
Implementation Method 1
utilizing enzymes like polymerase or ligase for sequencing by synthesis or ligation
Data Source
AI summary
The present invention relates to a sequencing method which allows for increased rates of sequencing and an increase in the density of sequencing data. The system may be based on next generation sequencing methods such as sequencing by synthesis (SBS) but uses multiple primers bound at different positions on the same nucleic acid strand.