Microarray Probe Redistribution for Uniform Nucleic Acid Enrichment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nucleic acid microarray technologies face challenges in achieving uniform enrichment of target sequences, leading to biased capture and downstream application issues, where some targets are disproportionately represented, affecting sequencing and other genetic analyses.
Innovation Solution
The development of microarray designs with redistributed probes that balance probe density across target regions to ensure uniform or intentionally non-uniform enrichment, using immobilized nucleic acid probes on solid supports like microarray slides or beads, allowing for hybridization, washing, and elution to enrich specific nucleic acid sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional microarray probe designs are used, then target nucleic acid enrichment is achieved, but uniformity of enrichment deteriorates due to biased capture where some targets are disproportionately represented
Solution Approach 1:
The patent applies local quality by redistributing probes non-uniformly across the microarray based on local characteristics of target regions. Probes are concentrated in regions with lower capture efficiency and thinned in regions with higher capture efficiency, so that each local area has appropriate probe density for its specific capture characteristics, achieving uniform overall enrichment.
Solution Approach 2:
The patent changes the spatial distribution parameter of probes from uniform to non-uniform arrangement. By adjusting probe density as a variable parameter across different regions of the microarray, the system compensates for regional variations in capture efficiency and achieves uniform enrichment of target nucleic acids.
2Reliability
If probe density is increased in all regions, then capture sensitivity is improved, but uniformity of enrichment deteriorates due to over-representation of certain targets
Solution Approach 1:
Instead of uniformly increasing probe density, the patent applies local quality by selectively concentrating probes only in regions that require it. Regions with low capture efficiency receive additional probes, while regions with high capture efficiency receive fewer probes, maintaining appropriate local probe densities that preserve both sensitivity and uniformity.
Solution Approach 2:
The patent applies partial action by providing probes to only those regions where they are needed based on capture efficiency analysis. Rather than excessively increasing probe density everywhere, the system applies probes partially and selectively to regions with deficient capture performance, avoiding waste and maintaining uniformity.
3Manufacturing precision
If probe redistribution is performed to achieve uniform enrichment, then uniformity of enrichment is improved, but device complexity increases due to redesigned microarray probe distribution
Solution Approach 1:
The patent applies preliminary action by performing probe redistribution design before the microarray is synthesized. The non-uniform probe distribution pattern is predetermined and built into the microarray construction process, eliminating the need for post-synthesis modifications and reducing overall system complexity despite the sophisticated probe arrangement.
Solution Approach 2:
The patent changes the probe distribution parameter from conventional uniform patterns to optimized non-uniform patterns that account for regional capture characteristics. This parameter change is implemented during microarray design and synthesis, avoiding subsequent complex manipulation steps and reducing operational complexity.
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 improves the uniformity of enrichment, ensuring that sequencing reads have approximately uniform distribution over target regions, enhancing the quality and utility of nucleic acid samples for downstream applications like sequencing and SNP detection.
Implementation Method 1
hybridizing the sample to probes immobilized on a solid support
Data Source
AI summary
The present invention provides methods and compositions for the enrichment of target nucleic acids in a microarray system. In particular, the present invention provides methods and compositions for uniform enrichment of target nucleic acid molecules in a microarray format. The present invention also provides for intentionally non-uniform enrichment among target nucleic acid molecules.