Xpandomer Expansion for Nucleic Acid Sequencing Throughput
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Solution Overview
Problem
Current DNA sequencing technologies, such as Sanger Sequencing and second-generation methods, face challenges in throughput, cost, and read length, making them inadequate for applications like whole genome sequencing in personalized medicine.
Innovation Solution
The method involves synthesizing a surrogate polymer, called an Xpandomer, which encodes nucleic acid information by template-directed assembly, increasing the linear separation of sequence data elements and facilitating detection through expanded length and enhanced signal strength.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If Sanger sequencing or second-generation methods are used, then sequencing can be performed with current technology, but throughput is limited and cost is high
Solution Approach 1:
The patent segments the sequencing process into two distinct phases: (1) template-directed assembly of nucleic acid information onto a surrogate polymer backbone, and (2) detection of the assembled structure. This segmentation allows parallel processing of multiple templates simultaneously, dramatically increasing throughput while reducing per-base cost through economies of scale
Solution Approach 2:
The patent introduces a surrogate polymer backbone as an intermediary carrier that temporarily holds the assembled nucleic acid information. This mediator enables the decoupling of assembly and detection steps, allowing high-throughput parallel assembly followed by efficient detection, thereby improving both throughput and cost-effectiveness
2Measurement precision
If nucleic acid sequences are determined using current methods, then sequence data can be obtained, but spatial resolution and detection accuracy are insufficient
Solution Approach 1:
The patent transitions from detecting individual nucleotide positions in one dimension to detecting the overall structure and composition of assembled nucleic acid information in multiple dimensions. The surrogate polymer backbone provides additional spatial dimensions for signal detection, enhancing spatial resolution and reducing information loss through redundant encoding
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 improves spatial resolution and sequencing accuracy, enabling high-throughput and cost-effective sequencing of nucleic acids by expanding the nucleotide separation and amplifying signal strength, suitable for applications like whole genome sequencing.
Implementation Method 1
a) providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to a contiguous nucleotide sequence
Implementation Method 2
b) cleaving the at least one selectively cleavable bond to yield an Xpandomer of a length longer than the plurality of the subunits of the daughter strand
Implementation Method 3
detecting the reporter elements of the Xpandomer
Data Source
AI summary
Nucleic acid sequencing methods and related products are disclosed. Methods for sequencing a target nucleic acid comprise providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to a contiguous nucleotide sequence of all or a portion of the target nucleic acid, wherein the individual subunits comprise a tether, at least one probe or nucleobase residue, and at least one selectively cleavable bond. The selectively cleavable bond(s) is/are cleaved to yield an Xpandomer of a length longer than the plurality of the subunits of the daughter strand, the Xpandomer comprising the tethers and reporter elements for parsing genetic information in a sequence corresponding to the contiguous nucleotide sequence of all or a portion of the target nucleic acid. Reporter elements of the Xpandomer are then detected. Corresponding products, including Xpandomers are also disclosed.