Rotatable Molecular Disk Strands for Faster Nucleic Acid Sequencing
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Solution Overview
Problem
Next-generation sequencing technologies are hindered by time-consuming and resource-intensive template and library preparation processes, including nucleic acid fragmentation, repair, and adaptor ligation, leading to significant sample loss and limited throughput.
Innovation Solution
The use of synthetic strands comprising rotatable molecular disks that bind to nucleobases (A, C, G, T/U) and indicate sequence through rotational positions, eliminating the need for fragmentation, repair, and adaptor ligation, and enabling rapid nucleic acid sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional library preparation procedures (fragmentation, repair, adaptor ligation) are used, then sequencing can be performed on existing platforms, but sample loss increases and throughput is limited
Solution Approach 1:
The patent extracts and eliminates the problematic library preparation steps (fragmentation, repair, adaptor ligation) from the sequencing workflow. By using synthetic strands with pre-attached adaptors and universal binding sites, the invention removes the need for these intermediate processing steps that cause sample loss and reduce throughput.
Solution Approach 2:
The synthetic strands are pre-prepared with universal binding sites and adaptor sequences already integrated into their structure. This preliminary preparation eliminates the need for time-consuming library preparation steps performed on each sample, thereby increasing throughput and reducing sample loss.
2Productivity
If traditional library preparation procedures are used, then sequencing can be performed, but the time and resources required for template and library preparation increase
Solution Approach 1:
The patent removes the time-consuming library preparation steps (fragmentation, repair, adaptor ligation) from the sequencing workflow. By using synthetic strands with pre-attached adaptors and universal binding sites, the invention eliminates these intermediate processing steps that consume significant time and resources.
Solution Approach 2:
The synthetic strands are pre-prepared with universal binding sites and adaptor sequences already integrated into their structure. This preliminary preparation eliminates the need for time-consuming library preparation steps performed on each sample, thereby increasing sequencing speed and reducing preparation time.
3Loss of time
If rotatable molecular disks are used for sequencing, then sequencing time is reduced, but the complexity of the sequencing system increases
Solution Approach 1:
The patent uses synthetic strands as simplified copies or models that capture the essential sequencing function without requiring complex biological processes. The synthetic strands with rotatable molecular disks represent a simplified system that maintains sequencing capability while reducing time requirements, despite increased structural complexity of the synthetic components.
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 allows for significantly faster nucleic acid sequencing by directly hybridizing to nucleic acids, reducing sequencing time and resource requirements compared to existing methods.
Implementation Method 1
molecular disks each comprising a first moiety that binds to adenine (A), a second moiety that binds to cytosine (C), a third moiety that binds to guanine (G), and a fourth moiety that binds to thymine (T), uracil (U), or both (T/U)
Implementation Method 2
The molecular disks enable hybridization of the synthetic strand to a nucleic acid, where the rotational positions of the molecular disks indicate the sequence of the nucleic acid
Data Source
AI summary
Provided are synthetic strands for nucleic acid sequencing. In some embodiments, the strands include a plurality of rotatable molecular disks. The plurality of rotatable molecular disks comprises molecular disks each comprising a first moiety that binds to adenine (A), a second moiety that binds to cytosine (C), a third moiety that binds to guanine (G), and a fourth moiety that binds to thymine (T), uracil (U), or both (T/U). The first, second, third, and fourth moieties are spaced about the perimeter of the molecular disk. The molecular disks enable hybridization of the synthetic strand to a nucleic acid, where the rotational positions of the molecular disks indicate the sequence of the nucleic acid. Also provided are methods of using the synthetic strands, as well as related compositions, kits, and nucleic acid sequencing systems. Stem-loop structure-based sequencing methods and related compositions, kits, and nucleic acid sequencing systems are also provided.