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Force-Controlled Formation of Dynamic Nanopores for Single-Biomolecule Sensing and Single-Cell Secretomics
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    Force-Controlled Formation of Dynamic Nanopores for Single-Biomolecule Sensing and Single-Cell Secretomics
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    • Tilman Schlotter
      Tilman Schlotter
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
    • Sean Weaver
      Sean Weaver
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
      More by Sean Weaver
    • Csaba Forró
      Csaba Forró
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
      Department of Chemistry, Stanford University, Stanford, California 94305, United States
      More by Csaba Forró
    • Dmitry Momotenko
      Dmitry Momotenko
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
    • János Vörös
      János Vörös
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
    • Tomaso Zambelli*
      Tomaso Zambelli
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
      *Email: [email protected]
    • Morteza Aramesh*
      Morteza Aramesh
      Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, 8092 Zürich, Switzerland
      Laboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, 8093 Zürich, Switzerland
      *Email: [email protected]
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    ACS Nano

    Cite this: ACS Nano 2020, 14, 10, 12993–13003
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    https://doi.org/10.1021/acsnano.0c04281
    Published September 11, 2020
    Copyright © 2020 American Chemical Society

    Abstract

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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 an inability to perform long-term recordings in complex solutions. Here we introduce a method for fast and precise on-demand formation of a nanopore with controllable size between 2 and 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.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.0c04281.

    • Experimental and data analysis, estimation of the nanopore size, FCNP formation on different PDMS substrates, noise characterization and electrochemical measurements in different solutions, translocation of nanoparticles and biomolecules, recording next to neurons (PDF)

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    This article is cited by 10 publications.

    1. Alexander Kiy, Shankar Dutt, Kasimir P. Gregory, Christian Notthoff, Maria Eugenia Toimil-Molares, Patrick Kluth. The Effect of Electrolyte Properties on Ionic Transport through Solid-State Nanopores: Experiment and Simulation. Langmuir 2024, 40 (40) , 20888-20896. https://doi.org/10.1021/acs.langmuir.4c01347
    2. Tilman Schlotter, Tom Kloter, Julian Hengsteler, Kyungae Yang, Lijian Zhan, Sujeni Ragavan, Haiying Hu, Xinyu Zhang, Jens Duru, János Vörös, Tomaso Zambelli, Nako Nakatsuka. Aptamer-Functionalized Interface Nanopores Enable Amino Acid-Specific Peptide Detection. ACS Nano 2024, 18 (8) , 6286-6297. https://doi.org/10.1021/acsnano.3c10679
    3. Kinga Dora Kovacs, Balint Beres, Nicolett Kanyo, Balint Szabó, Beatrix Peter, Szilvia Bősze, Inna Szekacs, Robert Horvath. Single-cell classification based on label-free high-resolution optical data of cell adhesion kinetics. Scientific Reports 2024, 14 (1) https://doi.org/10.1038/s41598-024-61257-2
    4. Xue Zhang, Zhuoqun Su, Yan Zhao, Di Wu, Yongning Wu, Guoliang Li. Recent advances of nanopore technique in single cell analysis. The Analyst 2024, 149 (5) , 1350-1363. https://doi.org/10.1039/D3AN01973J
    5. Annie Sahota, Anthony Monteza Cabrejos, Zoe Kwan, Binoy Paulose Nadappuram, Aleksandar P. Ivanov, Joshua B. Edel. Recent advances in single-cell subcellular sampling. Chemical Communications 2023, 59 (36) , 5312-5328. https://doi.org/10.1039/D3CC00573A
    6. Weichen Wei, Xuejiao Wang. Ion‐specific effects in confined nanochannels and neural network. Aggregate 2023, 4 (2) https://doi.org/10.1002/agt2.302
    7. Annina Stuber, Tilman Schlotter, Julian Hengsteler, Nako Nakatsuka. Solid-State Nanopores for Biomolecular Analysis and Detection. 2023, 283-316. https://doi.org/10.1007/10_2023_240
    8. Changjian Zhao, Kaiju Li, Xingyu Mou, Yibo Zhu, Chuan Chen, Ming Zhang, Yu Wang, Ke Zhou, Yingying Sheng, Hao Liu, Yunjin Bai, Xinqiong Li, Cuisong Zhou, Dong Deng, Jianping Wu, Hai-Chen Wu, Rui Bao, Jia Geng. High-fidelity biosensing of dNTPs and nucleic acids by controllable subnanometer channel PaMscS. Biosensors and Bioelectronics 2022, 200 , 113894. https://doi.org/10.1016/j.bios.2021.113894
    9. Mi Li, Lianqing Liu, Tomaso Zambelli. FluidFM for single-cell biophysics. Nano Research 2022, 15 (2) , 773-786. https://doi.org/10.1007/s12274-021-3573-y
    10. Christine Müller-Renno, Diana Remmel, Mario Braun, Kajohn Boonrod, Gabi Krczal, Christiane Ziegler. Producing Plant Virus Patterns with Defined 2D Structure. physica status solidi (a) 2021, 218 (18) https://doi.org/10.1002/pssa.202100259

    ACS Nano

    Cite this: ACS Nano 2020, 14, 10, 12993–13003
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.0c04281
    Published September 11, 2020
    Copyright © 2020 American Chemical Society

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