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1. False negative and false positive free nanopore fabrication via adaptive learning of the controlled dielectric breakdown

   Rosha, Kamyar; Tang, Zifan; Guan, Weihua (May 2019, Transducer 2019)

   We investigate the current transport characteristics in the electrolyte-dielectric-electrolyte structure commonly used in the in-situ controlled breakdown (CBD) fabrication of solid-state nanopores. It is found that the stochastic breakdown process could lead to fidelity issues of false positives (an incorrect indication of a true nanopore formation) and false negatives (inability to detect initial nanopore formation). Robust and deterministic detection of initial physical breakdown to alleviate false positives and false negatives is critical for precise nanopore size control. To this end, we report a high fidelity moving Z-Score method based CBD fabrication of solid-state nanopore. We demonstrate 100% success rate of realizing the initial nanopore conductance of 3±1 nS (corresponds to the size of 1.7±0.6 nm) regardless of the dielectric membrane characteristics. Our study also elucidates the Joule heating is the dominant mechanism for electric field-based nanopore enlargement. Single DNA molecule sensing using nanopores fabricated by this method was successfully demonstrated. We anticipate the moving Z-Score based CBD method could enable broader access to the solid state nanopore-based single molecule analysis. 

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2. Sapphire-Supported Nanopores for Low-Noise DNA Sensing

   https://doi.org/10.1109/MEMS51782.2021.9375372  

   Xia, Pengkun; Zuo, Jiawei; Choi, Shinhyuk; Chen, Xiahui; Bai, Jing; Wang, Chao (January 2021, 2021 IEEE 34th International Conference on Micro Electro Mechanical Systems (MEMS))

   null (Ed.)

   Solid-state nanopore sensors have broad applications from single-molecule biosensing to diagnostics and sequencing. Prevalent nanopore sensors are fabricated on silicon (Si) substrates through micromachining, however, the high capacitive noise resulting from Si conductivity has seriously limited both their sensing accuracy and recording speed. A new approach is proposed here for forming nanopore membranes on insulating sapphire wafers by anisotropic wet etching of sapphire through micro-patterned triangular masks. Reproducible formation of small membranes with an average dimension of ~10 μm are demonstrated. For validation, a sapphire-supported (SaS) nanopore chip, with a 100 times larger membrane area than silicon-supported (SiS) nanopore, showed 130 times smaller capacitance (10 pF) and ~2.5 times smaller rootmean-square (RMS) noise current (~20 pA over 100 kHz bandwidth). Tested with 1k bp 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 platform feasible for biosensing as well as a wide variety of MEMS applications. 

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3. Attention Mobilization as a Modulator of Listening Effort: Evidence from Pupillometry

   Johns, M. A.; Calloway, R. C.; Karunathilake, I. M.; Decruy, L. P.; Anderson, S.; Simon, J. Z.; Kuchinsky, S. E. (March 2024, Trends in hearing)

   Listening to speech in noise can require substantial mental effort, even among younger normal-hearing adults. The task-evoked pupil response (TEPR) has been shown to track the increased effort exerted to recognize words or sentences in increasing noise. However, few studies have examined the trajectory of listening effort across longer, more natural, stretches of speech, or the extent to which expectations about upcoming listening difficulty modulate the TEPR. Seventeen younger normal-hearing adults listened to 60-s-long audiobook passages, repeated three times in a row, at two different signal-to-noise ratios (SNRs) while pupil size was recorded. There was a significant interaction between SNR, repetition, and baseline pupil size on sustained listening effort. At lower baseline pupil sizes, potentially reflecting lower attention mobilization, TEPRs were more sustained in the harder SNR condition, particularly when attention mobilization remained low by the third presentation. At intermediate baseline pupil sizes, differences between conditions were largely absent, suggesting these listeners had optimally mobilized their attention for both SNRs. Lastly, at higher baseline pupil sizes, potentially reflecting over-mobilization of attention, the effect of SNR was initially reversed for the second and third presentations: participants initially appeared to disengage in the harder SNR condition, resulting in reduced TEPRs that recovered in the second half of the story. Together, these findings suggest that the unfolding of listening effort over time depends critically on the extent to which individuals have successfully mobilized their attention in anticipation of difficult listening conditions. 

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4. Noise in nanopore sensors: Sources, models, reduction, and benchmarking

   https://doi.org/10.1016/j.npe.2019.12.008  

   Liang, Shengfa; Xiang, Feibin; Tang, Zifan; Nouri, Reza; He, Xiaodong; Dong, Ming; Guan, Weihua (December 2019, Nanotechnology and Precision Engineering)

   Label-free nanopore sensors have emerged as a new generation technology of DNA sequencing and have been widely used for single molecule analysis. Since the first α-hemolysin biological nanopore, various types of nanopores made of different materials have been under extensive development. Noise represents a common challenge among all types of nanopore sensors. The nanopore noise can be decomposed into four components in the frequency domain (1/f noise, white noise, dielectric noise, and amplifier noise). In this work, we reviewed and summarized the physical models, origins, and reduction methods for each of these noise components. For the first time, we quantitatively benchmarked the root mean square (RMS) noise levels for different types of nanopores, demonstrating a clear material-dependent RMS noise. We anticipate this review article will enhance the understanding of nanopore sensor noises and provide an informative tutorial for developing future nanopore sensors with a high signal-to-noise ratio. 

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5. Over One Million DNA and Protein Events Through Ultra‐Stable Chemically‐Tuned Solid‐State Nanopores

   https://doi.org/10.1002/smll.202300198  

   Saharia, Jugal; Bandara, Yapa Mudiyanselage Nuwan Dhananjaya Yapa; Karawdeniya, Buddini Iroshika; Dwyer, Jason Rodger; Kim, Min Jun (April 2023, Small)

   Abstract Stability, long lifetime, resilience against clogging, low noise, and low cost are five critical cornerstones of solid‐state nanopore technology. Here, a fabrication protocol is described wherein >1 million events are obtained from a single solid‐state nanopore with both DNA and protein at the highest available lowpass filter (LPF, 100 kHz) of the Axopatch 200B–the highest event count mentioned in literature. Moreover, a total of ≈8.1 million events are reported in this work encompassing the two analyte classes. With the 100 kHz LPF, the temporally attenuated population is negligible while with the more ubiquitous 10 kHz, ≈91% of the events are attenuated. With DNA experiments, the pores are operational for hours (typically >7 h) while the average pore growth is merely ≈0.16 ± 0.1 nm h⁻¹. The current noise is exceptionally stable with traces typically showing <10 pA h⁻¹increase in noise. Furthermore, a real‐time method to clean and revive pores clogged with analyte with the added benefit of minimal pore growth during cleaning (< 5% of the original diameter) is showcased. The enormity of the data collected herein presents a significant advancement to solid‐state pore performance and will be useful for future ventures such as machine learning where large amounts of pristine data are a prerequisite. 

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