Nanopore Sequencing Polymer End Modification
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Solution Overview
Problem
Current nanopore-based analysis methods face challenges in establishing efficient initial interactions between polymer analytes and nanopores, particularly for long polymers and those with three-dimensional structures, leading to reduced accessibility and capture rates.
Innovation Solution
The method involves applying an electric field to translocate polymers through a nanopore and measuring ion current patterns, with the polymer end domains modified to include charged moieties that enhance interaction rates by increasing the energetic favorability for capture, using charged moieties such as phosphate groups attached to the ends of DNA analytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If long polymer analytes are used for sequencing, then more complete genomic information is obtained, but the interaction rate with nanopores decreases proportionally to the length of the polymer
Solution Approach 1:
The patent applies local quality by modifying only the terminal ends of the polymer analyte with charged moieties (such as phosphates or amino groups) while leaving the rest of the polymer unchanged. This localized modification enhances the interaction rate at the critical capture point (the terminal end) without altering the overall polymer structure or sequence information, thereby resolving the contradiction between maintaining complete genomic information and improving interaction efficiency
Solution Approach 2:
The patent changes the electrostatic parameter (charge) at the terminal ends of the polymer analyte by adding charged moieties. This parameter change increases the electrostatic interaction with the nanopore, thereby improving the interaction rate and capture efficiency for long polymers without affecting the sequencing information content
2Stability of the object's composition
If biopolymers are in their native three-dimensional structures, then they maintain their natural conformation, but the accessibility of terminal end subunits for nanopore interaction is reduced
Solution Approach 1:
The patent applies local quality by selectively modifying only the terminal ends of the polymer with charged moieties. This localized approach enhances the accessibility and interaction capability at the terminal ends without requiring global denaturation or structural changes to the polymer, thereby maintaining the stability of the overall polymer composition while improving terminal end accessibility for nanopore capture
3Device complexity
If no charged moieties are added to polymer ends, then the polymer structure remains simple, but the energetic favorability for nanopore capture is reduced
Solution Approach 1:
The patent applies local quality by adding charged moieties only at the terminal ends of the polymer analyte rather than throughout the entire structure. This minimal, localized modification improves capture efficiency and reliability at the critical interaction point while keeping the overall polymer structure relatively simple and avoiding extensive chemical complexity
Solution Approach 2:
The patent applies preliminary action by pre-modifying the terminal ends of the polymer analyte with charged moieties before the nanopore capture process. This preliminary modification ensures that the polymer is pre-configured with enhanced electrostatic properties for favorable interaction with the nanopore, thereby improving capture efficiency and reliability from the outset
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 increases the interaction and capture rates of polymer analytes with nanopores, improving analysis efficiency and sequencing performance, especially for long polymers and low copy numbers.
Implementation Method 1
applying an electric field sufficient to translocate the polymer through a nanopore
Implementation Method 2
monitoring a signal, such as an electrical signal, that is influenced by the physical properties of the polymer subunits as the polymer analyte passes through the nanopore opening
Data Source
AI summary
The present disclosure provides methods and reagents for improving nanopore-based analyses of polymers. Specifically, the disclosure provides a method of analyzing a polymer that includes a polymer analyte that contains an end domain that has at least one charged moiety. The disclosure also provides a method of increasing the interaction rate between a polymer analyte and a nanopore, wherein the polymer analyte contains an end domain that has at least one charged moiety. The disclosure also provide compositions for use with the described methods, including adapter compositions that contain charged moieties, such as phosphate or sulfate groups, and that are configured to being linked to an polymer analyte domain.