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      Nanopore extended field-effect transistor for selective single-molecule biosensing

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          Abstract

          There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry. We report on a polypyrrole functionalized nexFET, with controllable gate voltage that can be used to switch on/off, and slow down single-molecule DNA transport through a nanopore. This strategy enables higher molecular throughput, enhanced signal-to-noise, and even heightened selectivity via functionalization with an embedded receptor. This is shown for selective sensing of an anti-insulin antibody in the presence of its IgG isotype.

          Abstract

          Efficient detection of single molecules is vital to many biosensing technologies, which require analytical platforms with high selectivity and sensitivity. Ren et al. combine a nanopore sensor and a field-effect transistor, whereby gate voltage mediates DNA and protein transport through the nanopore.

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          Most cited references42

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          Electrostatic Focusing of Unlabeled DNA into Nanoscale Pores using a Salt Gradient

          Solid-state nanopores are sensors capable of analyzing individual unlabelled DNA molecules in solution. While the critical information obtained from nanopores (e.g., DNA sequence) is the signal collected during DNA translocation, the throughput of the method is determined by the rate at which molecules arrive and thread into the pores. Here we study the process of DNA capture into nanofabricated silicon nitride pores of molecular dimensions. For fixed analyte concentrations we find an increase in capture rate as the DNA length increases from 800 to 8,000 basepairs, a length-independent capture rate for longer molecules, and increasing capture rates when ionic gradients are established across the pore. In addition, we show that application of a 20-fold salt gradient enables detection of picomolar DNA concentrations at high throughput. The salt gradients enhance the electric field, focusing more molecules into the pore, thereby advancing the possibility of analyzing unamplified DNA samples using nanopores.
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            Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors.

            Small RNA molecules have an important role in gene regulation and RNA silencing therapy, but it is challenging to detect these molecules without the use of time-consuming radioactive labelling assays or error-prone amplification methods. Here, we present a platform for the rapid electronic detection of probe-hybridized microRNAs from cellular RNA. In this platform, a target microRNA is first hybridized to a probe. This probe:microRNA duplex is then enriched through binding to the viral protein p19. Finally, the abundance of the duplex is quantified using a nanopore. Reducing the thickness of the membrane containing the nanopore to 6 nm leads to increased signal amplitudes from biomolecules, and reducing the diameter of the nanopore to 3 nm allows the detection and discrimination of small nucleic acids based on differences in their physical dimensions. We demonstrate the potential of this approach by detecting picogram levels of a liver-specific miRNA from rat liver RNA.
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              Degenerate n-doping of few-layer transition metal dichalcogenides by potassium.

              We report here the first degenerate n-doping of few-layer MoS2 and WSe2 semiconductors by surface charge transfer using potassium. High-electron sheet densities of ~1.0 × 10(13) cm(-2) and 2.5 × 10(12) cm(-2) for MoS2 and WSe2 are obtained, respectively. In addition, top-gated WSe2 and MoS2 n-FETs with selective K doping at the metal source/drain contacts are fabricated and shown to exhibit low contact resistances. Uniquely, WSe2 n-FETs are reported for the first time, exhibiting an electron mobility of ~110 cm(2)/V·s, which is comparable to the hole mobility of previously reported p-FETs using the same material. Ab initio simulations were performed to understand K doping of MoS2 and WSe2 in comparison with graphene. The results here demonstrate the need of degenerate doping of few-layer chalcogenides to improve the contact resistances and further realize high performance and complementary channel electronics.
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                Author and article information

                Contributors
                yanjun.zhang@imperial.ac.uk
                alex.ivanov@imperial.ac.uk
                joshua.edel@imperial.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                19 September 2017
                19 September 2017
                2017
                : 8
                : 586
                Affiliations
                [1 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Department of Medicine, , Imperial College London, ; London, W12 0NN UK
                [2 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Department of Chemistry, , Imperial College London, ; London, SW7 2AZ UK
                [3 ]ISNI 0000 0004 1757 9434, GRID grid.412645.0, Tianjin Neurological Institute, , Tianjin Medical University General Hospital, ; Heping Qu, 300052 China
                [4 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Chemistry, , University of Cambridge, ; Cambridge, CB2 1EW UK
                [5 ]ISNI 0000 0001 0010 3972, GRID grid.35043.31, National University of Science & Technology MISIS, ; Moscow, 119049 Russia
                Author information
                http://orcid.org/0000-0003-1419-1381
                http://orcid.org/0000-0001-5870-8659
                Article
                549
                10.1038/s41467-017-00549-w
                5605549
                28928405
                c2b5eb13-131b-4122-87a7-0a0cdb826f0d
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 April 2017
                : 7 July 2017
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