Microparticle Delivery to Transmembrane Pores for Nanopore Sequencing
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Solution Overview
Problem
Current DNA sequencing technologies are slow and expensive due to reliance on amplification techniques and high quantities of fluorescent chemicals, and they struggle with efficient analyte delivery to transmembrane pores, limiting their sensitivity and efficiency.
Innovation Solution
The method involves attaching an analyte to a microparticle, which is then delivered to a transmembrane pore in a membrane, significantly reducing the amount of analyte required for detection and enhancing delivery efficiency by several orders of magnitude.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If amplification techniques are used to produce large volumes of polynucleotide, then detection sensitivity is improved, but sequencing speed and cost efficiency deteriorate
Solution Approach 1:
The invention extracts and eliminates the amplification step from the sequencing workflow by using nanopore technology that can directly detect single polynucleotide molecules without requiring large volumes of amplified DNA, thereby improving sequencing speed while maintaining detection sensitivity
Solution Approach 2:
The nanopore acts as an intermediary detection mechanism that translates single-molecule polynucleotide passage into measurable electrical current changes, enabling direct detection without amplification and resolving the contradiction between sensitivity and speed
2Measurement precision
If high quantities of fluorescent chemicals are used for signal detection, then detection sensitivity is improved, but cost and complexity increase
Solution Approach 1:
The invention replaces the chemical-based fluorescent detection system with an electrical measurement system using nanopores, where polynucleotide passage through the pore causes characteristic current blockades that can be detected without any fluorescent chemicals, thereby reducing both cost and complexity while maintaining sensitivity
Solution Approach 2:
The nanopore serves as an electrical intermediary that converts polynucleotide molecular information into electrical current signals, eliminating the need for fluorescent chemical mediators and simplifying the detection system
3Device complexity
If conventional analyte delivery methods are used, then system simplicity is maintained, but delivery efficiency and sensitivity deteriorate
Solution Approach 1:
The invention applies preliminary action by functionalizing microparticles with polynucleotide-binding proteins before introducing them to the nanopore system, which pre-concentrates and directs the analyte to the detection zone, thereby dramatically improving delivery efficiency without complicating the overall system
Solution Approach 2:
The functionalized microparticle acts as an intermediary carrier that bridges the gap between bulk solution and the nanopore detection zone, using protein-mediated binding to efficiently deliver polynucleotides to the pore while maintaining system simplicity
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 allows for ultra-low concentration analyte detection, increasing sequencing efficiency and reducing sample preparation complexity, enabling the characterization and sequencing of polynucleotides at much lower concentrations than previously possible.
Implementation Method 1
delivering the microparticle towards the membrane and thereby delivering the analyte to the transmembrane pore
Implementation Method 2
When a potential is applied across a nanopore, there is a change in the current flow when an analyte, such as a nucleotide, resides transiently in the barrel for a certain period of time
Data Source
AI summary
The invention relates to a new method of delivering an analyte to a transmembrane pore in a membrane. The method involves the use of microparticles.