Solution-Based Nucleic Acid Enrichment via Probe Extraction
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Solution Overview
Problem
Current nucleic acid microarray technologies face challenges in efficiently enriching targeted sequences due to substrate-associated variability, making it difficult to identify genetic variants and mutations associated with diseases, particularly in complex genomic regions like those found in cancer or genetic disorders.
Innovation Solution
The method involves using immobilized nucleic acid probes to capture target sequences from genomic samples in a solution-based format, allowing for the reduction of genetic complexity through hybridization, washing, and elution, followed by further amplification and analysis, providing a cost-effective and flexible approach for genetic analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If substrate-based microarray technology is used for sequence enrichment, then high-density parallel synthesis of oligonucleotide features is achieved, but substrate-associated variability and complexity reduce measurement precision and ease of operation
Solution Approach 1:
The patent extracts the oligonucleotide probes from the substrate-based microarray environment and transfers them to a solution-based format. This extraction eliminates substrate-associated variability while preserving the probes' hybridization functionality, thereby improving measurement precision without sacrificing productivity
Solution Approach 2:
The patent introduces solution-based hybridization as an intermediary step between probe synthesis and target sequence capture. This intermediary approach decouples the synthesis process from the enrichment process, allowing high-density parallel synthesis to be maintained while eliminating substrate variability that compromises measurement precision
2Productivity
If substrate-based microarray technology is used for sequence enrichment, then high-density parallel synthesis of oligonucleotide features is achieved, but device complexity and operational difficulty increase
Solution Approach 1:
By extracting probes from the complex substrate-based microarray system and placing them in solution, the patent dramatically simplifies the operational workflow. The solution-based format eliminates multiple substrate handling steps, washing protocols, and alignment requirements, making the enrichment process more straightforward while maintaining high productivity
Solution Approach 2:
The patent employs solution-based hybridization where probes and target sequences interact in liquid phase, allowing for simpler mixing, incubation, and separation operations compared to substrate-based methods. This hydraulic approach replaces complex mechanical substrate manipulation with fluid-based processes that are easier to standardize and automate
3Measurement precision
If whole genome resequencing is performed to identify genetic variants, then comprehensive variant detection is achieved, but time consumption and cost increase significantly
Solution Approach 1:
The patent extracts and enriches only the specific target sequences containing potential variants from the whole genome, rather than analyzing the entire genome. This targeted extraction approach maintains comprehensive variant detection capability for regions of interest while dramatically reducing the time and resources required compared to whole genome resequencing
Solution Approach 2:
Instead of performing complete whole genome resequencing, the patent applies partial action by focusing enrichment and analysis only on specific genomic regions of interest. This partial approach achieves sufficient variant detection completeness for clinical and research applications while reducing time consumption and costs
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 enables detailed genetic analysis of enriched target nucleic acids, facilitating the identification of genetic variants and mutations, and is applicable in various research and therapeutic contexts, including cancer and genetic disorder studies.
Implementation Method 1
The method involves using immobilized nucleic acid probes to capture target sequences from genomic samples in a solution-based format, allowing for the reduction of genetic complexity through hybridization
Data Source
AI summary
The present invention provides methods and systems for the capture and enrichment of target nucleic acids and analysis of the enriched target nucleic acids. In particular, the present invention provides for the enrichment of targeted sequences in a solution based format.