Nanopore Functionalized Electrodes DNA Base Detection
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Solution Overview
Problem
Current DNA sequencing technologies face challenges in achieving high accuracy and long contiguous reads due to limitations in interpreting electrical signals from DNA passing through nanopores, particularly with biological nanopores being unstable and difficult to interpret, and synthetic nanopores requiring precise control of tunnel gaps and molecular recognition.
Innovation Solution
A system utilizing a nanopore with functionalized electrodes and affinity elements that form hydrogen bonds with DNA bases, allowing for dynamic control of the tunnel gap and molecular recognition, enabling the detection of specific bases through measurable electrical currents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If biological nanopores are used for DNA sequencing, then the system can detect DNA passage through nanopores, but the nanopores are unstable and produce difficult-to-interpret signals
Solution Approach 1:
The patent creates solid-state nanopores that replicate the function of biological nanopores while eliminating their instability. The solid-state structure provides a stable, manufacturable platform that maintains the essential DNA translocation capability without the fragility of biological membranes.
Solution Approach 2:
The patent employs disposable DNA oligonucleotides that are temporarily functionalized with affinity elements for sequencing, then discarded after use. This approach simplifies the system by using inexpensive, single-use components rather than requiring stable, reusable biological nanopores.
2Reliability
If synthetic nanopores are used for DNA sequencing, then nanopore stability is improved, but precise control of tunnel gaps and molecular recognition is required
Solution Approach 1:
The patent divides the recognition function into separate components: the solid-state nanopore provides stable translocation, while discrete affinity elements (attached to DNA oligonucleotides) provide molecular recognition. This segmentation eliminates the need for complex integrated tunnel gap control mechanisms.
Solution Approach 2:
The patent introduces affinity elements as intermediaries between the DNA target and the detection system. These elements temporarily bind to complementary sequences, enabling specific base identification without requiring direct electronic tunneling through precisely controlled gaps.
3Measurement precision
If functionalized affinity elements are used for molecular recognition, then base identification accuracy is improved, but the system complexity increases
Solution Approach 1:
The patent employs DNA oligonucleotides that self-functionalize with affinity elements through hybridization. The system uses the natural complementary base-pairing properties of DNA to automatically position recognition elements at the correct locations, eliminating the need for complex external positioning or alignment mechanisms.
Solution Approach 2:
The patent changes the chemical state of the DNA by temporarily attaching affinity elements to oligonucleotides. This chemical modification enables specific molecular recognition while maintaining the simplicity of the overall system architecture, as the functionalization is achieved through standard biochemical techniques rather than complex device engineering.
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 enables accurate characterization of DNA bases with high fidelity, achieving 99.99% accuracy and allowing for parallel operation of multiple nanopores for efficient DNA sequencing.
Implementation Method 1
forms a temporary electrical circuit that can be used to characterize that portion of the biopolymer
Implementation Method 2
a force of 55 pN (where a base-to-base separation of 0.6 nm for stretched DNA was used)
Implementation Method 3
the constriction is provided with a functionalized unit which, together with a newly translocated portion of the biopolymer, forms a temporary electrical circuit
Data Source
AI summary
An system for recognition of a translocating polymeric target molecule includes a device having at least one constriction that is sized to permit translocation of only a single copy of the molecule. A pair of spaced apart sensing electrodes border the constriction, which may be a nanopore. The first electrode is connected to a first affinity element and the second electrode is connected to a second affinity element. Each affinity element may connected to its corresponding electrode via one or more intermediary compounds, such as a linker molecule and/or an electrode attachment molecule. The first and second affinity elements are configured to temporarily form hydrogen bonds with first and second portions of the target molecule as the latter passes through the constriction. During translocation, the electrodes affinity elements and first and second portions of the target molecule complete an electrical circuit and allow a measurable electrical current to pass between the first and second electrodes. The time-varying nature of this electrical current, and the specific affinity elements employed, allow one to characterize the target molecule.