Quaternary Directory Oligo Selection System
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Solution Overview
Problem
Current PCR-based methods lack an efficient search strategy for selectively amplifying target DNA and are inefficient in managing primer sequence length, leading to suboptimal nucleotide allocation and sequencing rates.
Innovation Solution
The introduction of a quaternary directory system for oligo subsets, inspired by computer science directory management, allows for hierarchical search and selection of oligo subsets using reversible and irreversible terminators, reducing the need for extensive primer regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR-based methods are used for selective amplification, then sensitivity and specificity are improved, but the search efficiency and sequencing rate deteriorate
Solution Approach 1:
The patent segments the oligo library into hierarchical subsets using a directory system. Instead of treating all oligos uniformly, it organizes them into levels (e.g., Level 1: A/G/C/T, Level 2: AA/AG/AC/AT, etc.), allowing selective amplification at different hierarchical levels. This segmentation enables efficient search strategies that can target specific subsets without processing the entire library, thereby improving sequencing rate while maintaining specificity.
Solution Approach 2:
The patent introduces a hierarchical dimension to the traditional linear primer binding approach. By adding the directory level dimension, the system can select oligos based on multiple criteria simultaneously (e.g., first base, second base, etc.), transforming the selection process from simple presence/absence detection to multi-level hierarchical search, which improves both efficiency and accuracy.
2Measurement precision
If primer sequence length is increased to secure specificity, then detection accuracy is improved, but nucleotide allocation efficiency deteriorates
Solution Approach 1:
The patent segments the primer binding region into multiple hierarchical levels, where each level corresponds to a specific nucleotide position. Instead of requiring a long continuous primer sequence, the system uses shorter primers that bind at different hierarchical levels. For example, a Level 1 primer binds to the first nucleotide, while a Level 2 primer binds to the second nucleotide, allowing the same specificity to be achieved with shorter primers at each level.
Solution Approach 2:
The patent applies partial action by using primers that bind to only specific portions of the oligo sequence at hierarchical levels. Rather than requiring primers to span the entire target region, the system uses partial binding at each level to achieve cumulative specificity. This partial action approach reduces the total nucleotide allocation required while maintaining the desired detection accuracy.
3Adaptability or versatility
If universal primer regions are assigned to both ends to amplify entire oligo library, then coverage is improved, but primer region allocation becomes inefficient
Solution Approach 1:
The patent segments the primer region allocation into hierarchical levels, where each level has its own dedicated primer binding sites. Instead of using universal primers at both ends for the entire library, the system allocates specific primer regions at each hierarchical level (Level 1, Level 2, etc.). This segmentation allows the same primer region to be reused across multiple oligos at different levels, reducing overall complexity while maintaining comprehensive coverage.
Solution Approach 2:
The patent applies universality by designing primer regions that can serve multiple functions at different hierarchical levels. A primer region at Level 1 can bind to multiple oligos that share the same first nucleotide, and this same region can be used for Level 2 primers that bind to oligos with specific second nucleotides. This multi-functional design reduces the total number of unique primer regions needed while maintaining broad coverage across the entire oligo library.
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 enables efficient, selective, and specific detection and expansion of oligo subsets, improving sequencing rates and minimizing nucleotide allocation, thus enhancing the scalability and programmability of oligo selection processes.
Implementation Method 1
a composition for selecting a target nucleic acid from a complex mixture of nucleic acids by selective hybridization
Data Source
AI summary
The polymerase chain reaction (PCR) has limitations, including a lack of efficient search strategies and inefficiencies in securing primer sequence lengths, despite its high sensitivity and specificity. Therefore, the present invention has been devised to address these issues, concerning a composition for the selection of the desired nucleic acid and a method for nucleic acid selection using it. By using the composition and method of the present invention, it becomes possible to hierarchically, efficiently, and selectively detect and amplify subsets of oligonucleotides with high specificity, which is expected to be widely utilized in the overall bio/medical field.