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Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs

View ORCID ProfileT. Ono, K. Kamada, R. Hayashi, A. R. Piacenti, C. Gabbutt, N. Sriwilaijaroen, H. Hiramatsu, Y. Kanai, K. Inoue, S. Nakakita, T. Kawahara, Y. Ie, Y. Watanabe, Y. Suzuki, S. Contera, K. Matsumoto
doi: https://doi.org/10.1101/2020.03.18.996884
T. Ono
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
2JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan
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  • ORCID record for T. Ono
  • For correspondence: t-ono@sanken.osaka-u.ac.jp sonia.antoranzcontera@physics.ox.ac.uk k-matsumoto@sanken.osaka-u.ac.jp
K. Kamada
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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R. Hayashi
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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A. R. Piacenti
3Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford, OX1 3PU, UK
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C. Gabbutt
3Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford, OX1 3PU, UK
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N. Sriwilaijaroen
4Research Institute for Life and Health Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan
5Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand
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H. Hiramatsu
6Department of Clinical Engineering, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan
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Y. Kanai
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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K. Inoue
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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S. Nakakita
7Department of Functional Glycomics, Life Science Research Center, Kagawa University, Miki-cho, Kagawa 761-0793, Japan
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T. Kawahara
6Department of Clinical Engineering, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan
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Y. Ie
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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Y. Watanabe
8Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Y. Suzuki
4Research Institute for Life and Health Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan
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S. Contera
3Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford, OX1 3PU, UK
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  • For correspondence: t-ono@sanken.osaka-u.ac.jp sonia.antoranzcontera@physics.ox.ac.uk k-matsumoto@sanken.osaka-u.ac.jp
K. Matsumoto
1Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
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  • For correspondence: t-ono@sanken.osaka-u.ac.jp sonia.antoranzcontera@physics.ox.ac.uk k-matsumoto@sanken.osaka-u.ac.jp
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Abstract

Small solid-state devices are candidates for accelerating biomedical assays/drug discovery, however their potential remains unfulfilled. Here, we demonstrate that graphene-field effect transistors (FET) can be used to successfully detect the key molecular events underlying viral infections and the effect of antiviral drugs. Our device success is achieved by bio-mimicking the host-cell surface during an influenza infection at the graphene channel. In-situ AFM confirms the biological interactions at the sialic acid-functionalized graphene: viral hemagglutinin (HA) binds to sialic acid, and neuraminidase (NA) reacts with the sialic acid-HA complex. The graphene-FET detects HA binding to sialic acid, and NA cleavage of sialic acid. The inhibitory effect of the drug “zanamivir” on NA-sialic acid interactions is monitored in real-time; the reaction rate constant of NA-sialic acid reaction was successfully determined. We demonstrate that graphene-FETs are powerful platforms for measurement of biomolecular interactions and contribute to future deployment of solid-state devices in drug discovery/biosensing.

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Posted March 20, 2020.
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Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs
T. Ono, K. Kamada, R. Hayashi, A. R. Piacenti, C. Gabbutt, N. Sriwilaijaroen, H. Hiramatsu, Y. Kanai, K. Inoue, S. Nakakita, T. Kawahara, Y. Ie, Y. Watanabe, Y. Suzuki, S. Contera, K. Matsumoto
bioRxiv 2020.03.18.996884; doi: https://doi.org/10.1101/2020.03.18.996884
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Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs
T. Ono, K. Kamada, R. Hayashi, A. R. Piacenti, C. Gabbutt, N. Sriwilaijaroen, H. Hiramatsu, Y. Kanai, K. Inoue, S. Nakakita, T. Kawahara, Y. Ie, Y. Watanabe, Y. Suzuki, S. Contera, K. Matsumoto
bioRxiv 2020.03.18.996884; doi: https://doi.org/10.1101/2020.03.18.996884

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