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Design Principles of DNA-Barcodes for Nanopore-FET Readout, Based on Molecular Dynamics and TCAD Simulations
Aderik Voorspoels1,2, Juliette Gevers1,2, Sybren Santermans1
1Imec, Kapeldreef 75, B-3001 Leuven, Belgium.
The Journal of Physical Chemistry. A
|May 7, 2024
Summary
This study demonstrates a new DNA barcode design for nanopore field-effect transistor (NP-FET) sensors. Optimized NP-FETs achieve a record 78 kbit·s-1 bit-rate for high-throughput DNA analysis.
Area of Science:
- Nanotechnology and Nanoscience
- Molecular Biology and Genetics
- Electrical Engineering and Computer Science
Background:
- Nanopore field-effect transistor (NP-FET) devices offer sensitive, parallelized, on-chip readout for single-molecule sensing.
- NP-FETs are promising for large-scale molecular analysis, including proteomics and high-throughput DNA barcode readout.
- Current understanding of NP-FET bit-rate capabilities for DNA barcode sensing is limited.
Purpose of the Study:
- To investigate the bit-rate performance of NP-FET devices for DNA-based barcode sensing.
- To design and optimize DNA barcodes, considering label size and spacing, for enhanced NP-FET readout.
- To establish a new benchmark for NP-FET bit-rate capabilities in DNA analysis.
Main Methods:
- Design of DNA barcodes using dumbbell-like DNA structures labeled onto double-stranded DNA.
- Molecular dynamics (MD) simulations to account for DNA origami conformational fluctuations in label size selection.
- Development of an experimentally informed 3D continuum nanofluidic-nanoelectronic device model to predict ionic current and FET signals.
- Simulation of a generic NP-FET with a 14 nm pore under experimental conditions.
Main Results:
- A DNA barcode design for a 14 nm pore NP-FET was developed.
- Optimizing label spacing to half the pore length achieved a bit-rate of 78 kbit·s-1.
- This bit-rate significantly surpasses the current state-of-the-art (≈40 kbit·s-1) with potential for further improvement.
- NP-FET readout offers advantages including larger signal size and sinusoidal signal shape.
Conclusions:
- The study establishes a new record for NP-FET bit-rate performance in DNA barcode sensing.
- Optimized DNA barcode design and NP-FET parameters are crucial for achieving high-throughput molecular analysis.
- NP-FET technology demonstrates significant potential for advancing sensitive, rapid, and parallelized molecular detection.
