NCAFM2023 Programme Booklet

Monday 1620 - 1640

SCANNNG ION CONDUCTANCE MICROSCOPY (SICM) FOR BIOLOGICAL AND MATERIAL SCIENCE APPLICATIONS

Petr Gorelkin 1,2 , Alexander Erofeev 1,2, Vasilii Kolmogorov 2 , Pavel Novak 1,3 , Andrew Shevchuk 1,3 , Christopher Edwards 1,3 , Yuri Korchev 1,3 1 ICAPPIC Limited, The Fisheries, Mentmore Terrace, London, E8 3PN, United Kingdom 2 National University of Science and Technology “MISiS”, Moscow, Russia Imperial College London, Du Cane Road, London, W12 0NN, United Kingdom Email: pg@icappic.com

The SICM probe a nanopipette is ideally suited for performing nanoscale assays on the cell surface. These include patch-clamp recording from individual surface structures, iontophoretic delivery of reagents, or pressure micro-application via the pipette to probe mechanical properties of the cell or to deliver reagents. Until now, these advantages of SICM have never been fully explored in such important preparations as brain slices or cell cultures with a complex surface topology because the requirement for a relatively flat specimen surface has been intrinsic to standard scanning probe techniques. We can clearly resolve fine dendritic segments, even those “suspended” in space [1]. In order to unambiguously identify synaptic connections, we combined this new imaging mode with fluorescence and nanomechanical imaging [2]. We observed how the mechanical properties of single cells changed in the presence of drugs acting on a cytoskeleton [3]. We observed how the mechanical properties of single cells changed in the presence of drugs acting on various parts of the cytoskeleton. We have also shown the possibility of applying low-stress SICM for long-term nanomechanical mapping in real-time and the visualization of the dynamic process related to the changes in the mechanical properties of the living cells. This technology is fast enough to observe relatively rapid biological events. We have successfully combined scanning nanopipettes with principles of electrophysiology, fluorescence microscopy, electrochemistry, electrophoresis, and electroosmosis to investigate single channels and receptors in cellular membranes, to deliver biomolecules to precisely defined locations in cell cultures, and to perform single cell analysis [4]. Also, we have demonstrated applications of scanning ion conductance microscopy for nanoscale activity mapping of electrodes for ion batteries and investigating of nanoscale electrochemical properties of novel materials. With recent progress in nanopore-based biosensing and sequencing, and nanopipette-based 3D printing we are only just beginning to open a new window into the life at nanoscale and realizing new possibilities for engineering of interfaces between single cells and man-made electronics for therapeutic and diagnostic purposes or synthesis of entirely novel bioelectrical circuits and materials.

References [1] P. Novak et al., Nature Methods., 6(4), 279-81 (2009) [2] V.S. Kolmogorov et al., Nanoscale, 13, 6558-6568 (2021) [3] A.E. Machulkin et al., J. Med. Chem. 64, 23, 17123–17145, (2021) [4] Y. Zhang et al., Nature Communications, 10, 5610 (2019)

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