2019 EPFL doctorate Award - Finalist – Adrian Nievergelt

The observation of bio-molecular processes at a single-molecule level requires a microscope that is capable of resolving soft structures at nanometer precision. Additionally, a fast acquisition rate is required in order to be able to resolve the dynamic behavior of molecules, such as their motion, binding and unbinding as well as conformational changes. The atomic force microscope (AFM) is a mechanical microscope that uses a force sensor with a sharp tip to probe a surface point by point. Traditionally, AFM is a relatively slow technique. In my thesis I have developed instrumentation, techniques and analysis methods for high-speed atomic force microscopy, which is capable of obtaining images in a matter of seconds instead of minutes. The developed instrument is user friendly, open-source and capable of imaging delicate samples such as the dynamic assembly and disassembly of weakly-interacting proteins such as the centriolar scaffolding protein SAS-6. I have demonstrated the capabilities of the developed hardware on a broad variety of specimens, from polymer science over membrane biophysics and whole cell imaging to the self-assembly of molecules into larger ordered structures.