Rotatable Solid Supports for Direct Nucleic Acid Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current next-generation sequencing technologies are hindered by time-consuming and resource-intensive library preparation processes, including nucleic acid fragmentation, repair, and platform-specific adaptor ligation, which limit their speed and throughput.
Innovation Solution
The development of synthetic strands with rotatable solid supports that bind to adenine, cytosine, guanine, and thymine/uracil nucleobases, enabling direct hybridization and sequencing without the need for fragmentation or repair, using a base strand comprising materials like carbon nanotubes or nanofibers, and position markers to indicate rotational positions for sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional library preparation procedures (fragmentation, repair, adaptor ligation) are used, then sequencing accuracy is maintained, but sequencing time increases and throughput decreases
Solution Approach 1:
The patent applies preliminary action by pre-assembling synthetic strands with rotatable solid supports that have pre-positioned nucleobase-binding moieties (A, C, G, T/U) and position markers. These synthetic strands are prepared in advance with all necessary components, eliminating the need for time-consuming library preparation steps including fragmentation, repair, and adaptor ligation during actual sequencing operations.
Solution Approach 2:
The invention extracts and eliminates the time-consuming library preparation steps (fragmentation, repair, adaptor ligation) from the sequencing workflow. By using pre-fabricated synthetic strands with integrated binding moieties and position markers, the patent removes these intermediate preparation procedures entirely, allowing direct hybridization to nucleic acids for immediate sequencing.
2Productivity
If conventional library preparation procedures are used, then complete nucleic acid processing is achieved, but sample loss increases
Solution Approach 1:
The synthetic strands are pre-assembled with all necessary functional components (rotatable solid supports, nucleobase-binding moieties, position markers) before use. This preliminary preparation ensures that the strands are ready for direct hybridization, minimizing handling steps and reducing sample loss that typically occurs during multiple library preparation operations.
3Speed
If rotatable solid supports with position markers are used, then sequencing speed increases, but device complexity increases
Solution Approach 1:
The patent segments the sequencing function into distinct modular components: rotatable solid supports, nucleobase-binding moieties (A, C, G, T/U), and position markers. Each solid support is an independent unit that can rotate to present the correct binding moiety, and each component has a specific function. This segmentation allows for systematic operation and detection while maintaining manageable complexity through functional modularity.
Solution Approach 2:
The solid supports are designed to be rotatable rather than fixed, introducing dynamic movement to the system. Each solid support can rotate to present the appropriate nucleobase-binding moiety to the target nucleic acid sequence. This dynamic capability enables the synthetic strand to adapt its configuration during hybridization, improving sequencing speed while the rotational mechanism itself remains a relatively simple mechanical degree of freedom.
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 reduces sequencing time and eliminates the need for polymerases and synthesis steps, enabling faster and more efficient nucleic acid sequencing with improved throughput.
Implementation Method 1
Hybridization between a synthetic strand and a nucleic acid via base pairing creates a duplex in which relative orientation of the position markers are fixed.
Data Source
AI summary
Provided are synthetic strands for nucleic acid sequencing. In some embodiments, the strands include a plurality of rotatable solid supports. The plurality of rotatable solid supports comprises solid supports each comprising on its surface a first moiety that binds to adenine (A), a second moiety that binds to cytosine (C), a third moiety that binds to guanine (G), a fourth moiety that binds to thymine (T), uracil (U), or both (T/U). Each of such solid supports further comprises on its surface a position marker that indicates the rotational position of the solid support, where the first, second, third, and fourth moieties are spaced about the circumference of the solid support. The solid supports enable hybridization of the synthetic strand to a nucleic acid. Also provided are methods of using the synthetic strands, as well as related compositions, kits, and nucleic acid sequencing systems.