High-throughput DNA Synthesis Detection via Mixed Library Sequencing
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Solution Overview
Problem
Current on-chip DNA synthesis technologies face high error rates and increased costs due to the complexity of oligonucleotide libraries and the inefficiency of traditional Sanger sequencing for accuracy measurement and product screening.
Innovation Solution
A high-throughput detection method utilizing mixed libraries and high-throughput sequencing technology to reduce costs and improve accuracy, involving the construction of mixed sequencing libraries, sequencing, and error removal processes to achieve base accuracy rates of 100%.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Sanger sequencing is used to measure accuracy rate and screen accurate fragments, then measurement precision is achieved, but cost increases significantly
Solution Approach 1:
The patent uses high-throughput sequencing technology to create digital copies and sequences of DNA fragments, replacing the need for expensive Sanger sequencing. By sequencing multiple clones in parallel and using bioinformatic assembly, the system achieves accurate consensus sequences at lower cost, directly addressing the contradiction between measurement precision and cost.
Solution Approach 2:
The patent combines multiple low-accuracy DNA fragments from different clones into a consensus sequence through bioinformatic assembly. By merging information from multiple sequences, the system achieves high measurement precision for the final assembled sequence while avoiding the need for expensive individual Sanger sequencing of each fragment.
2Reliability
If multiple clones are selected for Sanger sequencing to ensure high success rate, then reliability is improved, but productivity decreases
Solution Approach 1:
The patent sequences multiple clones in parallel using high-throughput sequencing technology, creating digital copies that can be processed simultaneously. This allows reliable consensus assembly from multiple sources without the sequential time constraints of Sanger sequencing, thereby maintaining high reliability while dramatically improving productivity.
Solution Approach 2:
The patent performs preliminary high-throughput sequencing of multiple clones before final assembly. By preparing and sequencing multiple candidate clones in advance, the system ensures that accurate sequences are available for assembly, maintaining high reliability while enabling parallel processing that improves overall productivity.
3Manufacturing precision
If traditional DNA synthesis and assembly methods are used, then manufacturing precision is maintained, but cost increases
Solution Approach 1:
The patent synthesizes multiple copies of DNA fragments on microarray chips and uses high-throughput sequencing to verify accuracy. By creating redundant copies and using computational assembly, the system achieves high manufacturing precision while reducing the cost per base pair compared to traditional methods that require expensive Sanger sequencing verification.
Solution Approach 2:
The patent changes the verification parameter from expensive Sanger sequencing to more cost-effective high-throughput sequencing. By altering the detection method while maintaining assembly accuracy through bioinformatic consensus, the system achieves the same manufacturing precision at lower cost.
4Quantity of substance
If on-chip DNA synthesis is used to reduce cost, then cost decreases, but measurement precision of accuracy rate deteriorates
Solution Approach 1:
The patent combines sequences from multiple clones synthesized on-chip into a consensus sequence through bioinformatic assembly. By merging information from multiple lower-precision individual sequences, the system achieves high measurement precision for the final assembled sequence while maintaining the cost advantages of on-chip synthesis.
Solution Approach 2:
The patent uses high-throughput sequencing to create accurate digital copies of the synthesized DNA fragments. By sequencing multiple copies and using computational consensus, the system overcomes the limitations of direct experimental verification, achieving high measurement precision at lower cost than traditional methods.
Data Source
AI summary
Disclosed is a high-throughput detection method for a DNA synthesis product. According to the method of the present invention, a high-throughput sequencing technology is applied to detection of a DNA chip synthesis product through a mixed library construction strategy, so that costs of product detection and accurate product screening are reduced.