Nucleic Acid Sequencing via Immobilized Template Segmentation
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Solution Overview
Problem
Current nucleic acid sequencing technologies are expensive and lack the speed, accuracy, and long read lengths necessary for efficient diagnostics and treatment of genetic diseases.
Innovation Solution
A method for high-throughput nucleic acid sequencing that involves immobilizing nucleic acid molecules with sequence homology to a target molecule on a support coupled to a detector. The method incorporates a subset of nucleotides or nucleotide analogs with a detectable moiety and a terminating subunit, and another subset without these features, allowing for sequence determination through detection of the detectable moiety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing sequencing technology is used, then sequencing can be performed, but the cost is expensive and the speed and accuracy are insufficient for diagnostic applications
Solution Approach 1:
The patent segments the nucleic acid template into multiple copies immobilized on a solid support, allowing parallel sequencing reactions. Each nucleic acid molecule is individually addressed and sequenced simultaneously, improving both accuracy through multiple measurements and speed through parallel processing
Solution Approach 2:
The patent introduces a solid support as an intermediary between the nucleic acid template and the detection system. The support immobilizes nucleic acid molecules and positions them for detection, enabling accurate and efficient sequencing while reducing background noise and improving signal detection
2Length of moving object
If existing sequencing technology is used, then sequencing can be performed, but the read length is limited and cannot achieve long sequence reads
Solution Approach 1:
The patent performs preliminary actions by immobilizing multiple copies of the nucleic acid template on the support before sequencing begins. This preparation allows the sequencing reaction to proceed continuously without repeated template preparation steps, enabling longer read lengths and reducing total sequencing time
Solution Approach 2:
The patent maintains continuous useful action by keeping nucleic acid molecules immobilized on the support throughout the sequencing process. The continuous presence of templates allows uninterrupted sequencing reactions and signal detection, achieving both long read lengths and high speed
3Ease of manufacture
If existing sequencing technology is used, then sequencing can be performed, but the cost is too high for widespread clinical application
Solution Approach 1:
The patent uses copying by immobilizing multiple copies of the nucleic acid template on the solid support. This allows a single template to generate multiple sequencing signals, increasing throughput and reducing the cost per sequence while maintaining high accuracy through signal averaging
Solution Approach 2:
The patent creates a universal platform where the solid support can accommodate various nucleic acid templates and sequencing reactions. This multi-functional system can process different samples and applications using the same infrastructure, reducing overall costs and enabling high-throughput clinical applications
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
Enables the determination of nucleic acid sequences of relatively long lengths with high accuracy, addressing the limitations of existing sequencing technologies in terms of speed, cost, and read length.
Implementation Method 1
each of the first subset of nucleotides or nucleotide analogs comprises a detectable moiety and a terminating subunit
Data Source
AI summary
The present disclosure provides methods and systems for determining a nucleic acid sequence of a target nucleic acid molecule. A method for sequencing a target nucleic acid molecule comprises subjecting a plurality of nucleic acid molecules exhibiting sequence homology to the target nucleic acid molecule to at most 4000 cycles a nucleic acid extension reaction while measuring detectable signals from the plurality of nucleic acid molecules. The detectable signals may correspond to individual nucleotides or nucleotide analogs incorporated into the plurality of nucleic acid molecules during the nucleic acid extension reaction. The detectable signals may be used to generate a sequence of the target nucleic acid molecule at a length of at least about 500 bases and an accuracy of at least about 97%.