Zero-Mode Waveguide with Built-In Electrodes for DNA Capture
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Solution Overview
Problem
Current single-molecule DNA sequencing technologies face challenges with loading efficiency and length bias, requiring high DNA input and purified libraries to mitigate short DNA length bias, and existing zero-mode waveguides are mechanically fragile and prone to optical background noise.
Innovation Solution
The development of zero-mode waveguides with built-in electrodes that apply an electric field using a thin metallic film and dielectric spacer, allowing for efficient electrophoretic DNA capture at picogram levels without the need for free-standing membranes, enhancing mechanical stability and reducing optical noise.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If free-standing membranes are used in zero-mode waveguides, then DNA capture efficiency is improved, but mechanical stability deteriorates
Solution Approach 1:
The patent replaces the mechanical free-standing membrane structure with an electric field-based capture mechanism. Built-in electrodes generate electric fields that draw DNA molecules into the waveguide, eliminating the need for mechanically fragile membranes while maintaining high capture efficiency.
Solution Approach 2:
The invention changes the fundamental capture mechanism from passive mechanical diffusion through membranes to active electrophoretic capture using electric fields. This parameter change allows for both high efficiency and mechanical stability by using electrical forces rather than mechanical structures.
2Productivity
If conventional zero-mode waveguides are used, then DNA sequencing is performed, but optical background noise increases
Solution Approach 1:
The patent extracts and removes the source of optical background noise by eliminating free-standing membranes and using built-in electrodes instead. This extraction of the harmful element reduces optical noise while preserving the sequencing functionality.
3Productivity
If high DNA input is used, then loading efficiency is improved, but cost and complexity increase
Solution Approach 1:
The patent replaces passive mechanical loading with active electrophoretic loading using built-in electrodes. This substitution enables efficient DNA capture at low input concentrations by using electrical fields to actively draw molecules into the waveguide, reducing the quantity of DNA required.
4Productivity
If electrophoretic DNA capture is implemented, then DNA loading efficiency is improved, but device complexity increases
Solution Approach 1:
The patent merges the electrode structure directly into the waveguide fabrication process, combining multiple functions into a single integrated structure. This merging reduces overall device complexity by eliminating separate membrane components and simplifying the fabrication steps.
Solution Approach 2:
The built-in electrodes serve multiple functions: they provide electrical contact for electrophoretic capture, serve as structural elements of the waveguide, and enable precise positioning of DNA molecules. This multi-functionality reduces the need for additional components, simplifying the overall device.
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 improves DNA loading efficiency by several orders of magnitude, reduces fabrication costs, and enables high-throughput sequencing with reduced length bias, allowing for accurate radial positioning and longer device lifetime.
Implementation Method 1
Application of a voltage to the electrode layer with the use of proper electrolyte allows efficient electrophoretic DNA capture at picogram levels
Implementation Method 2
the electrically conductive layer, when energized with a given polarity relative to an electrically conductive element in a sample at the sample interface layer, produces an electric field from the electrically conductive layer through the well to the electrically conductive element
Data Source
AI summary
A system and apparatus are provided for sensing a molecule in a sample for identifying the molecule in the sample. Also provided is a method of manufacturing an apparatus for sensing a molecule in a sample. The system and apparatus may contain a composition of a mixture of a buffer solution and a sample solution containing a sample. The apparatus contains a series of wells. The sample is deposited into the system and a molecule having an electric charge in the sample attaches to a layer in a well of the apparatus, allowing for a sensor connected to the apparatus to identify the molecule.