Multimer Structure for Accurate Short Nucleic Acid Sequencing
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Solution Overview
Problem
Nanopore sequencing technologies face challenges in accurately sequencing short nucleic acid fragments due to high error rates and inability to distinguish between mutations and errors introduced during PCR amplification, limiting their suitability for diagnosing genetic diseases.
Innovation Solution
A multimer structure comprising multiple units with unique indices, identifiers, and end-marking sequences allows for accurate sequencing of short nucleic acid segments by platforms designed for long nucleic acid fragments, enabling error differentiation and origin identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If nanopore sequencing is used to sequence short nucleic acid fragments, then sequencing speed and simplicity are improved, but sequencing accuracy deteriorates
Solution Approach 1:
The patent divides the sequencing process into multiple segments by using multiple indices and identifiers attached to different portions of the nucleic acid fragment. This allows the short fragment to be sequenced multiple times from different origins, and the results are combined to achieve high accuracy while maintaining the speed advantage of nanopore sequencing.
Solution Approach 2:
The patent creates multiple copies of the same nucleic acid fragment by attaching different indices and identifiers to it, then sequences each copy separately. By comparing the sequences from multiple copies, the system can distinguish between true mutations and sequencing errors, thereby improving accuracy without sacrificing speed.
2Quantity of substance
If PCR amplification is used to prepare nucleic acid fragments for sequencing, then sufficient material is obtained, but sequencing errors are introduced
Solution Approach 1:
The patent introduces indices and identifiers as intermediary elements that are attached to the nucleic acid fragments before sequencing. These intermediaries allow the system to track the origin of each fragment and distinguish between fragments that went through PCR amplification and those that did not, enabling error differentiation while maintaining adequate material quantity.
Solution Approach 2:
The patent implements a feedback mechanism where the sequence data from multiple indexed fragments is analyzed and compared. This feedback allows the system to identify and filter out errors introduced during PCR amplification, retaining only the accurate sequences for diagnostic purposes.
3Measurement precision
If multiple indices and identifiers are attached to nucleic acid segments, then error differentiation capability is improved, but preparation complexity increases
Solution Approach 1:
The patent merges multiple functions into a single integrated approach by combining indices, identifiers, and the nucleic acid fragment into a unified structure. This allows the system to achieve error differentiation capability while managing preparation complexity through a coordinated, multi-component system rather than separate independent processes.
Data Source
AI summary
A multimer configured to allow sequencing and sequence analysis of at least one nucleic acid segment, the multimer comprising multiple units, wherein each unit comprising: a segment comprising a target nucleic acid sequence to be sequenced and analyzed; and at least one separator positioned at least at one side of the segment. Additional embodiments of the multimer and the unit as well as method for preparing the unit and multimer, and method for analyzing sequences of the multimer and unit, are disclosed herein.