@article{a39e4292e6cd4018b17e9618adacc703,
title = "Sapphire-supported nanopores for low-noise DNA sensing",
abstract = "Solid-state nanopores have broad applications from single-molecule biosensing to diagnostics and sequencing. The high capacitive noise from conventionally used conductive silicon substrates, however, has seriously limited both their sensing accuracy and recording speed. A new approach is proposed here for forming nanopore membranes on insulating sapphire wafers to promote low-noise nanopore sensing. Anisotropic wet etching of sapphire through micro-patterned triangular masks is used to demonstrate the feasibility of scalable formation of small (<25 μm) membranes with a size deviation of less than 7 μm over two 2-inch wafers. For validation, a sapphire-supported (SaS) nanopore chip with a 100 times larger membrane area than conventional nanopores was tested, which showed 130 times smaller capacitance (10 pF) and 2.6 times smaller root-mean-square (RMS) noise current (18–21 pA over 100 kHz bandwidth, with 50–150 mV bias) when compared to a silicon-supported (SiS) nanopore (~1.3 nF, and 46–51 pA RMS noise). Tested with 1k base-pair double-stranded DNA, the SaS nanopore enabled sensing at microsecond speed with a signal-to-noise ratio of 21, compared to 11 from a SiS nanopore. This SaS nanopore presents a manufacturable nanoelectronic platform feasible for high-speed and low-noise sensing of a variety of biomolecules.",
keywords = "DNA sensing, Low capacitance, Low noise, Sapphire etching, Scalable membrane fabrication, Signal-to-noise ratio",
author = "Pengkun Xia and Jiawei Zuo and Pravin Paudel and Shinhyuk Choi and Xiahui Chen and {Rahman Laskar}, {Md Ashiqur} and Jing Bai and Weisi Song and Im, {Jong One} and Chao Wang",
note = "Funding Information: This work is partially supported by the Arizona State University ( ASU ) startup funds to Chao Wang. Pengkun Xia, Jiawei Zuo, Xiahui Chen, Shinhyuk Choi, Jing Bai and Md Ashiqur Rahman Laskar acknowledge support from National Science Foundation under grant no. 1711412 , 1809997 , 1838443 , 1847324 , 2020464 , and 2027215 . The nanopore chips were fabricated in the NanoFab and Eyring Materials Center (EMC) at Arizona State University. Access to the NanoFab and/or EMC was supported, in part, by NSF grant no. ECCS-1542160. We thank Amanda Hoyt, John Crozier, and Jonathan Klane for their help in establishing the sapphire etching protocol. We thank Dr. Gustavo Stolovitzky at IBM, Prof. Amit Meller at Technion - Israel Institute of Technology, Dr. Yann Astier and Dr. Juraj Topolancik from Roche Sequencing Solutions, Dr. Stuart Lindsay at ASU, and Dr. Pei Pang (currently with Roswell Biotechnologies) at ASU for fruitful technical discussions. We appreciate Sunanda Vittal for proof-reading the manuscript. Funding Information: Solid-state nanopores have broad applications from single-molecule biosensing to diagnostics and sequencing. The high capacitive noise from conventionally used conductive silicon substrates, however, has seriously limited both their sensing accuracy and recording speed. A new approach is proposed here for forming nanopore membranes on insulating sapphire wafers to promote low-noise nanopore sensing. Anisotropic wet etching of sapphire through micro-patterned triangular masks is used to demonstrate the feasibility of scalable formation of small (<25 ?m) membranes with a size deviation of less than 7 ?m over two 2-inch wafers. For validation, a sapphire-supported (SaS) nanopore chip with a 100 times larger membrane area than conventional nanopores was tested, which showed 130 times smaller capacitance (10 pF) and 2.6 times smaller root-mean-square (RMS) noise current (18?21 pA over 100 kHz bandwidth, with 50?150 mV bias) when compared to a silicon-supported (SiS) nanopore (~1.3 nF, and 46?51 pA RMS noise). Tested with 1k base-pair double-stranded DNA, the SaS nanopore enabled sensing at microsecond speed with a signal-to-noise ratio of 21, compared to 11 from a SiS nanopore. This SaS nanopore presents a manufacturable nanoelectronic platform feasible for high-speed and low-noise sensing of a variety of biomolecules.This work is partially supported by the Arizona State University (ASU) startup funds to Chao Wang. Pengkun Xia, Jiawei Zuo, Xiahui Chen, Shinhyuk Choi, Jing Bai and Md Ashiqur Rahman Laskar acknowledge support from National Science Foundation under grant no. 1711412, 1809997, 1838443, 1847324, 2020464, and 2027215. The nanopore chips were fabricated in the NanoFab and Eyring Materials Center (EMC) at Arizona State University. Access to the NanoFab and/or EMC was supported, in part, by NSF grant no. ECCS-1542160. We thank Amanda Hoyt, John Crozier, and Jonathan Klane for their help in establishing the sapphire etching protocol. We thank Dr. Gustavo Stolovitzky at IBM, Prof. Amit Meller at Technion - Israel Institute of Technology, Dr. Yann Astier and Dr. Juraj Topolancik from Roche Sequencing Solutions, Dr. Stuart Lindsay at ASU, and Dr. Pei Pang (currently with Roswell Biotechnologies) at ASU for fruitful technical discussions. We appreciate Sunanda Vittal for proof-reading the manuscript. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",
year = "2021",
month = feb,
day = "15",
doi = "10.1016/j.bios.2020.112829",
language = "English (US)",
volume = "174",
journal = "Biosensors and Bioelectronics",
issn = "0956-5663",
publisher = "Elsevier Ltd",
}