EPFL Doctorate Award - 2024 - Samuel Mendes Leitão

For his developments in high-speed scanning ion conductance microscopy and the invention of scanning ion conductance spectroscopy.

Microscopy techniques, such as electron microscopy, super-resolution optical microscopy, and atomic force microscopy (AFM), have been applied to image the structure of cells in great detail. The major challenge is to obtain 3D information at nanometer resolution without affecting the viability of the cells and avoiding interference with the process. The thesis presents the development of a time-resolved scanning ion conductance microscope (SICM), from concept to prototype, capable of resolving spatiotemporal biological processes with unprecedented resolution and imaging speed. By integrating advances in nanopositioning, controls theory, microelectronics, and nanopore fabrication, the time-resolved SICM system enabled sub-5 nm resolution, performed high-speed imaging of 0.5 s per image, and allowed large imaging volumes of eukaryotic cells.

In addition to imaging, time-resolved SICM was successfully adapted for single-molecule spectroscopy using nanopores, creating a new technique called scanning ion conductance spectroscopy (SICS). SICS overcame limitations in nanopore technology by controlling the nanopores' position and the translocation speed of individual molecules. The increased detection capability with SICS has the potential to be transferable to other solid-state and biological nanopore methods, significantly improving diagnostic and sequencing applications.