Patterned Substrate Nucleic Acid Fragmentation
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Solution Overview
Problem
Current methods for generating nucleic acid fragments of uniform length are complex and not compatible with multi-well plate formats or laboratory information management systems, making them inefficient for automation and tracking.
Innovation Solution
The method involves linearly stretching nucleic acids over substrates with consistently spaced cleavage regions and then cleaving them to produce uniform fragments, using techniques like photolithographic patterning, molecular combing, or surface-tethered stretching, followed by collection of the fragments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If traditional methods are used to generate nucleic acid fragments, then fragment generation is achieved, but the process is complex and not compatible with automation systems
Solution Approach 1:
The patent replaces complex mechanical and manual operations with a simplified surface-based system. Nucleic acids are stretched on patterned surfaces with defined geometry, eliminating the need for complex mechanical fragment generation equipment. This substitution enables automation compatibility while reducing process complexity.
Solution Approach 2:
The invention changes the physical state and configuration parameters of nucleic acids by stretching them on patterned surfaces. This parameter change from random coil to linear stretched conformation enables precise fragment length control through surface pattern geometry, simplifying the overall process and enabling automation.
2Productivity
If manual methods are used for nucleic acid fragmentation, then flexibility is maintained, but efficiency and throughput are reduced
Solution Approach 1:
The patent segments the nucleic acid molecules by stretching them across patterned surfaces with defined cleavage regions. This segmentation approach allows parallel processing of multiple molecules simultaneously on the surface, dramatically increasing throughput while maintaining operational simplicity through standardized surface patterns.
Solution Approach 2:
The invention transitions from one-dimensional manual manipulation to two-dimensional surface-based processing. Nucleic acids are stretched across surface patterns, enabling parallel fragment generation across the surface area, which increases productivity while maintaining ease of operation through standardized surface protocols.
3Manufacturing precision
If non-uniform fragmentation is used, then process simplicity is maintained, but sequencing accuracy and computational requirements increase
Solution Approach 1:
The patent applies local quality by creating specific regions on the surface with defined cleavage patterns. Different areas of the surface have specific geometric features that control fragment length at local positions, achieving uniform fragment generation while using relatively simple overall surface structures.
Solution Approach 2:
The invention performs preliminary action by pre-patterning surfaces with defined cleavage regions before nucleic acid processing. This pre-established geometric framework ensures uniform fragment length without requiring complex real-time control during the fragmentation process, balancing precision with manageable system complexity.
Data Source
AI summary
Methods of generating nucleic acid fragments of substantially uniform length from sample nucleic acids comprising linearly stretching the sample nucleic acids over a substrate having a plurality of cleavage regions separated by relatively consistent distances, cleaving the linearly stretched sample nucleic acids at the cleavage regions, and collecting the resulting nucleic acid fragments. The method may further include collecting and concentrating the resultant nucleic acid fragments of substantially uniform length.