Experimental study of protein translocation through MoS2 nanopores

Gu, Chaoming; Yu, Zhoubin; Li, Xiaojie; Zhu, Xiaoqin; Cao, Zhen; Liu, Yang; Jin, Chuanhong; Liu, Yang

doi:10.1063/1.5128499

Cited by 20 publications

(12 citation statements)

References 34 publications

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“…Basic electrical testing of TFT nanopores is conducted prior to their immersion in solutions (Figure S3 of the Supporting Information). The devices are subsequently assembled with the top and bottom fluidic reservoirs, which are wetted and filled with ionic solutions following the protocols described in previous works , and the Methods. Device characterization includes measuring the ionic current, I p , and the TFT drain current, I d , under various voltage biases, as shown in Figure a.…”

Section: Resultsmentioning

confidence: 99%

“…The chip is then mounted onto an open window in a printed circuit board (PCB) and sealed by polydimethylsiloxane (PDMS). The PCB is clamped between two polytetrafluoroethylene (PTFE) fluidic half cells and sealed by silicone O rings to form a gigaohm seal. ,, Photos of the assembly are given in Figure S4 of the Supporting Information. After wetting and filling ionic solution into the reservoirs, Ag/AgCl electrodes are immersed in the two reservoirs to supply the transmembrane bias.…”

Section: Methodsmentioning

confidence: 99%

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Monolithic Integration of Vertical Thin-Film Transistors in Nanopores for Charge Sensing of Single Biomolecules

Zhu

et al. 2021

ACS Nano

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We propose and fabricate solid-state nanopore devices that monolithically integrate solution-gated, vertical thin-film transistors (TFTs) inside the nanopores for charge-based sensing of translocating biomolecules. The TFTs consist of zinc oxide semiconductor channels and aluminum oxide gate dielectrics, which are both conformally deposited along the inner surfaces of the nanopores via atomic layer deposition. The resultant TFT channel lengths and nanopore diameters both reach the ∼10 nm range. In translocation experiments using λ-DNAs or bovine serum antibody (BSA) proteins, the TFT−nanopore devices demonstrate concurrent detection of the ion conductance blockade signals and modulation signals in the TFT electrical current. The TFT signals show opposite signs for the negatively charged DNAs and positively charged BSAs as well as staircase signal shapes that correspond to the folding and knotting of λ-DNAs. Further experiments under various electrical biases and solution ionic strengths show that the ion blockade signals and the TFT signals have different dependence upon these experimental conditions. The TFT signals are analyzed to be consistent with the field effect sensing of the biomolecular charge, and the induced mirror charge is estimated from the signal amplitudes. This study could be a step forward to achieve charge-based single-biomolecular technology for basic research as well as for biosensing applications. It may also stimulate the development of TFT technologies for conformal integration of semiconductor electronics at the front end of nanostructures.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Monolithic Integration of Vertical Thin-Film Transistors in Nanopores for Charge Sensing of Single Biomolecules

Zhu

et al. 2021

ACS Nano

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“…BSA translocations were identified by a drop in the current (contrary to the previous measurements with DNA, peptide, and nanoparticles, e.g., see Figure 3), suggesting that the pore blockade by BSA contributes more than charge screening in the recorded currents. Through conventional solid-state nanopores, translocation times below 2 ms 48,49 are reported. Translocation times with the FCNP were in the order of 250 to 500 ms (Figure 4j,k), that is, 2 orders of magnitude longer.…”

Section: Resultsmentioning

confidence: 99%

Force-Controlled Formation of Dynamic Nanopores for Single-Biomolecule Sensing and Single-Cell Secretomics

et al. 2020

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Nanopore sensing of single nucleotides has emerged as a promising single-molecule technology for DNA sequencing and proteomics. Despite the conceptual simplicity of nanopores, adoption of this technology for practical applications has been limited by a lack of pore size adjustability and inability to perform long-term recordings in complex solutions. Here we introduce a method for fast and precise ondemand formation of a nanopore with controllable size between 2-20 nm through force-controlled adjustment of the nanospace formed between the opening of a microfluidic device (made of silicon nitride) and a soft polymeric substrate. The introduced nanopore system enables stable measurements at arbitrary locations. By accurately positioning the nanopore in the proximity of single neurons and continuously recording single molecule translations over several hours we have demonstrated this is a powerful approach for single cell proteomics and secretomics.

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“…Thus, baseline processing is particularly important to extract maximum possible events, especially in vigorously fluctuating current profiles. Such current fluctuations are more apparent in 2D materials such as graphene, hexagonal boron nitride (h-BN), and molybdenum disulfide (MoS 2 ) and somewhat less in silicon nitride (Si x N y ) pores fabricated using controlled dielectric breakdown (CDB) and chemically tuned CDB (CT-CDB), as will be shown later. Thus, the noise level depends on the fabrication method and device architecture. , The noise and baseline fluctuations can be quantified through, for example, power spectral density graphs and root mean square of the open-pore current as a function of time.…”

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confidence: 88%

Nanopore Data Analysis: Baseline Construction and Abrupt Change-Based Multilevel Fitting

et al. 2021

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Solid-state nanopore technology delivers single-molecule resolution information, and the quality of the deliverables hinges on the capability of the analysis platform to extract maximum possible events and fit them appropriately. In this work, we present an analysis platform with four baseline fitting methods adaptive to a wide range of nanopore traces (including those with a step or abrupt changes where pre-existing platforms fail) to maximize extractable events (2× improvement in some cases) and multilevel event fitting capability. The baseline fitting methods, in the increasing order of robustness and computational cost, include arithmetic mean, linear fit, Gaussian smoothing, and Gaussian smoothing and regressed mixing. The performance was tested with ultra-stable to vigorously fluctuating current profiles, and the event count increased with increasing fitting robustness prominently for vigorously fluctuating profiles. Turning points of events were clustered using the dbscan method, followed by segmentation into preliminary levels based on abrupt changes in the signal level, which were then iteratively refined to deduce the final levels of the event. Finally, we show the utility of clustering for multilevel DNA data analysis, followed by the assessment of protein translocation profiles.

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Experimental study of protein translocation through MoS2 nanopores

Cited by 20 publications

References 34 publications

Monolithic Integration of Vertical Thin-Film Transistors in Nanopores for Charge Sensing of Single Biomolecules

Monolithic Integration of Vertical Thin-Film Transistors in Nanopores for Charge Sensing of Single Biomolecules

Force-Controlled Formation of Dynamic Nanopores for Single-Biomolecule Sensing and Single-Cell Secretomics

Nanopore Data Analysis: Baseline Construction and Abrupt Change-Based Multilevel Fitting

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