Nanopore FET DNA Sequencing Device
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Solution Overview
Problem
Current DNA sequencing techniques, such as chain termination, pyrosequencing, and 454 Sequencing, rely on PCR, which limits their ability to accurately sequence long DNA strands due to primer annealing issues, RNA contamination, and secondary DNA structure reading problems, resulting in low nucleotide detection capacities, especially for repetitive genomes, and are slow and chemically expensive.
Innovation Solution
A nanopore-based DNA sequencing device with a nanopore integrated into the gate area of a field-effect transistor (FET) or quantum well transistor, using a voltage bias across fluid chambers to detect single nucleotides by modulating the source-drain current, eliminating the need for PCR and minimizing signal disturbances from stray capacitances and resistances.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional nanopore sequencing is used with a small pore diameter to detect single nucleotides, then measurement precision is improved, but device complexity increases due to the need for extremely small and thin pores
Solution Approach 1:
The patent combines the nanopore detection function with a field-effect transistor structure, merging the pore formation step into standard semiconductor manufacturing processes. The nanopore is integrated into the gate area of the FET, allowing the detector to function both as a transistor and as a nanopore sensor, thereby reducing device complexity while maintaining single-nucleotide resolution
Solution Approach 2:
The FET structure serves multiple functions: it provides the nanopore for DNA translocation, acts as the detection sensor through its channel current modulation, and offers standard semiconductor fabrication compatibility. This multi-functionality eliminates the need for separate complex pore structures while achieving high measurement precision
2Quantity of substance
If PCR-based sequencing techniques are used, then DNA amplification is achieved, but productivity decreases due to slow cycling steps and large chemical requirements
Solution Approach 1:
The patent extracts the DNA amplification step (PCR) from the sequencing process entirely. By using direct nanopore sequencing on native DNA molecules, the method eliminates the time-consuming PCR cycling steps and large chemical requirements, thereby dramatically improving productivity while still achieving sufficient DNA quantity for sequencing
Solution Approach 2:
The nanopore sequencing method enables continuous translocation and detection of DNA molecules through the pore without interruption by thermal cycling steps. DNA molecules can be sequenced in real-time as they pass through the nanopore, maintaining continuous useful action and significantly increasing sequencing throughput compared to discontinuous PCR cycles
3Quantity of substance
If PCR-based techniques are used for DNA sequencing, then DNA amplification is possible, but reliability decreases due to primer annealing issues, RNA contamination, and secondary structure problems
Solution Approach 1:
The patent removes PCR and all associated reliability issues from the sequencing process. By directly sequencing native DNA molecules through the nanopore without amplification, the method eliminates primer annealing problems, RNA contamination risks, and secondary structure formation that plague PCR-based techniques, thereby significantly improving sequencing reliability
Solution Approach 2:
The nanopore sequencing method allows DNA molecules to be sequenced in their native state without requiring external amplification services. The detector directly reads the sequence information as DNA translocates through the pore, with the DNA itself serving as the template without needing PCR-generated copies, thus improving reliability through self-service sequencing
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 direct, high-resolution detection of individual nucleotides, overcoming PCR limitations and achieving accurate, fast, and cost-effective whole-genome sequencing by utilizing the transistor's sub-nanometer thickness for precise nucleotide identification.
Implementation Method 1
A voltage bias across a membrane causes ions to flow through the nanopore 12 between two ion-containing solutions
Implementation Method 2
This device uses a nanopore for the confinement of a sample under test (for example nucleotides of a DNA strand) close to a sensor
Data Source
AI summary
A detector device and method of its fabrication are disclosed. Illustratively, an additional via is present through an insulator layer over a gate channel region which is on top of the channel region. The additional via is filled with conductor material. The conductor material is removed to form a chamber leading to one side of the gate channel region. Furthermore, a nanopore is etched from the chamber through the channel region.