Graphene Nanogap for Single-Molecule DNA Sequencing
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Solution Overview
Problem
Current DNA sequencing technologies are time and resource intensive due to short read lengths, require DNA amplification which can introduce errors, and struggle with sequencing large homopolymeric segments like telomeres.
Innovation Solution
The development of graphene nanogaps for DNA sequencing, which allows for the measurement of transverse conductance of individual DNA bases as they translocate through the nanogap, enabling single-molecule sequencing without amplification and potentially achieving longer read lengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Sanger sequencing method is used, then sequencing accuracy is achieved, but read length is short and process is time-intensive
Solution Approach 1:
The patent replaces the mechanical/chemical Sanger sequencing process with a nanopore-based electrical measurement system. DNA molecules translocate through a nanopore under an electric field, and different bases are identified by their distinct electrical signals as they pass through the pore, eliminating the need for chain-terminating nucleotides and gel electrophoresis.
Solution Approach 2:
The patent changes the measurement parameter from optical/chemical detection in Sanger sequencing to electrical conductance measurement in nanopore sequencing. By applying a voltage across the nanopore and measuring current changes as bases translocate, the system achieves both long read lengths and base identification accuracy through electrical signal variations.
2Quantity of substance
If DNA amplification (PCR) is performed, then sufficient DNA material is obtained, but errors are introduced and cost increases
Solution Approach 1:
The nanopore sequencing device can process single DNA molecules directly without requiring amplification. The system is designed to sequence individual molecules as they translocate through the nanopore, eliminating the need for PCR amplification steps that introduce errors and increase costs.
Solution Approach 2:
The patent extracts the amplification step from the sequencing workflow entirely. By designing the nanopore system to handle single molecules directly, the harmful amplification process is removed, allowing sequencing of native DNA without introducing polymerase errors or artifacts.
3Productivity
If miniaturization with microfluidics is implemented, then readout speed improves and material volume reduces, but device complexity increases
Solution Approach 1:
The patent replaces complex microfluidic systems with a simpler nanopore-based electrical measurement system. Instead of using microfluidics to control and detect DNA, the system uses a nanopore in a membrane with electrodes on either side, where DNA translocation is driven by an electric field and detected by current measurements.
Solution Approach 2:
The patent uses electrical signal variations (analogous to color changes in optical detection) to identify different bases. As each base translocates through the nanopore, it produces a characteristic electrical signal pattern that allows base identification without requiring complex optical detection systems.
4Measurement precision
If transverse conductance measurement is used, then single-base resolution is achieved, but fabrication of aligned nanoelectrodes is challenging
Solution Approach 1:
The patent merges the nanopore membrane and the electrode system into a single integrated structure. The nanopore is formed in a thin membrane with electrodes deposited on both sides, eliminating the need for separate, precisely aligned nanoelectrodes. The membrane itself becomes the structural element that positions the measurement point.
Solution Approach 2:
The nanopore membrane acts as an intermediary between the electrodes and the DNA molecule. Instead of requiring direct electrode-DNA contact or precise nanoelectrode alignment, the membrane with its embedded nanopore provides a stable, reproducible measurement interface where DNA translocation can be detected electrically.
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 potentially enables rapid, cost-effective, and accurate DNA sequencing with longer read lengths, avoiding the limitations of current technologies such as PCR amplification and short Sanger read lengths.
Implementation Method 1
measurement of transverse conductance of individual DNA bases as they translocate through the nanogap
Implementation Method 2
a DNA molecule translocates through it under the influence of an applied transmembrane electric field acting on the negatively charged backbone
Data Source
AI summary
Processes for conductive material nanogap formation have been developed that include: providing a base material, wherein the base material is either solid or comprises a micropore that extends through the first layered material, and wherein the micropore comprises a top opening, a bottom opening, and a volume boundary, applying a conductive material sheet to the first layered material, wherein the conductive material sheet covers the top opening of the micropore, applying two conducting electrodes to the conductive material sheet, so that each one of the conducting electrodes is positioned on either side of the micropore, applying an etch mask that covers at least a part of the conductive material sheet, the top opening of the micropore (if present), or a combination thereof, applying a passivation layer over at least the etch mask, fabricating a hole in the passivation layer directly above the top opening of the micropore, and applying at least one voltage pulse through the at least one conducting electrode to create a nanogap in the conductive material sheet, wherein the nanogap is over and open to the top opening of the micropore. In some embodiments, the micropore and the nanogap are fabricated simultaneously.