Adapter Molecule for Nanopore DNA Sequencing Reciprocation
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Solution Overview
Problem
The nanopore DNA sequencing method faces challenges in reliably reciprocating biomolecules through the nanopore for accurate analysis due to fast passage speed, which complicates the measurement of blocking currents derived from each base.
Innovation Solution
An adapter molecule with a three-dimensional structure formation domain and fall-off prevention portions is used to bind to the biomolecule, allowing for controlled reciprocation through the nanopore by forming a stable complex that prevents falling out and enables accurate analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If DNA strands pass through the nanopore at natural speed, then the nanopore sequencing method achieves high output and low running cost, but the passage speed is too fast (1 μs or less per base) to sufficiently measure the blocking current derived from each base
Solution Approach 1:
The patent introduces adapter molecules as intermediary components that bind to the ends of DNA strands. These adapter molecules contain specific structures (hairpin structures, complementary sequences) that enable controlled reciprocating motion of the DNA through the nanopore. The adapter acts as a mediator between the DNA and the nanopore system, allowing the DNA to be conveyed back and forth multiple times for repeated measurement, thereby improving measurement accuracy without requiring changes to the DNA itself or the nanopore structure.
2Measurement precision
If the passage speed of DNA through the nanopore is increased to 100 μs or more per base for accurate measurement, then the measurement accuracy improves, but the natural fast passage speed (1 μs or less per base) cannot be sufficiently controlled
Solution Approach 1:
The patent implements periodic reciprocating motion of the DNA strand through the nanopore. The adapter molecules enable the DNA to pass through the nanopore multiple times in a periodic manner, with each pass providing measurement opportunities. This periodic action allows the system to accumulate measurement data over multiple passes, effectively controlling the measurement timing and improving accuracy while maintaining the natural fast passage speed of the DNA.
Solution Approach 2:
The adapter molecules are pre-bound to the ends of the DNA strands before the sequencing process. These adapters contain pre-configured structures (such as hairpin loops and complementary sequences) that enable the reciprocating motion. By preparing the DNA-adapter complex in advance, the system eliminates the need for real-time control mechanisms during the actual sequencing, simplifying the operation while ensuring controlled reciprocation.
3Measurement precision
If adapter molecules are used to control reciprocation of biomolecules through the nanopore, then measurement accuracy improves, but the device complexity increases due to the need for adapter molecules and their complex structures
Solution Approach 1:
The adapter molecules are designed to be self-assembling and self-functional. The hairpin structures and complementary sequences in the adapters enable automatic formation of the required structures through base pairing and hybridization. The adapters self-regulate the reciprocating motion without requiring external control mechanisms, and the system uses the natural properties of the adapter-DNA complex to achieve controlled passage through the nanopore. This self-service approach reduces the need for complex external control systems.
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
The adapter molecule complex enables reliable and accurate analysis of biomolecules by controlling their passage through the nanopore, improving measurement accuracy and preventing errors in base sequence determination.
Implementation Method 1
a three-dimensional structure formation domain consisting of a single-stranded nucleotide
Implementation Method 2
the biomolecule is transferred to the second liquid tank through the nanopore according to a diffusion phenomenon and the generated potential gradient
Implementation Method 3
a potential gradient is generated in the nanopore in accordance with the applied voltage
Data Source
AI summary
A biomolecule is more easily and reliably reciprocated in a nanopore. An adapter molecule that directly or indirectly binds to a biomolecule to be analyzed comprises a three-dimensional structure formation domain consisting of a single-stranded nucleotide.