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Microscopy - Making optimal use of photons and electrons

Periodic Reporting for period 2 - MicroMOUPE (Microscopy - Making optimal use of photons and electrons)

Reporting period: 2019-09-01 to 2021-02-28

MICROMOUPE stands for ‘Microscopy – Making Optimal Use of Photons and Electrons’. The project aims at enhancing both light and electron microscopy, with a focus on phase microscopy techniques. Phase microscopy with light is typically used to study the morphology of cells. More recently it has been advanced to the detection and characterization of single proteins. Phase microscopy with electrons is used in cryogenic electron microscopy, one of the most successful techniques for the determination of the atomic structure of proteins. MICROMOUPE aims at enhancing the sensitivity of these techniques using wave-front shaping and cavity enhanced microscopy.
Wave-front shaping: On the one hand, optical wave-front shaping techniques will be used to adapt a microscope to a specific sample, optimizing sensitivity throughout the field of view. On the other hand a wave-front shaping tool based on electron-light interaction will be developed for electron beams, opening up new possibilities for electron optics.
Cavity enhancement: Letting a probe particle interact with a sample multiple times, multiplies the signal, contrast, and signal/noise that is to be expected from such a measurement. This has obvious applications when it comes to the detection of faint signals. In addition to that, multi-passing also increases the signal/noise per interaction of a probe-particle with the sample, which is beneficial for fragile biological samples, where dose has to be minimized. Within the MICROMOUPE project full field of view cavity enhanced microscopes are being developed for optical protein detection, as well as for electron microscopy.
Within the first reporting period, the project MicroMOUPE was initiated at the University of Vienna. A team of physicists and biologists was formed to carry out the proposed research. The laboratory up and running, and first results are being generated, as reported on in numerous invited and contributed talks at international conferences by members of the newly established ‘Quantum Microscopy and Biophysics’ group.
Within these first 18 months, two optical microscopes were designed and set-up, one of them for pushing sensitivity limits of multi-pass microscopy, the other one for sensitivity enhanced measurements using wave-front shaping. The latter one is sketched in Figure 1: In a simple add-on to a commercial microscope, a spatial light modulator allows optimizing the microscope for a specific sample. Both microscopes are currently under test and are optimized with respect to their performance. In addition to that, different cavity enhanced microscopy schemes were analyzed theoretically.
When it comes to electron microscopy, a setup was installed that should allow us to test wave-front shaping based on ponderomotive potentials. Currently all necessary components of the setup are being tested individually, their full integration is one of the main goals for the next period. Additionally, an electron optical design for a first multi-pass TEM was finalized in co-operation with Stanford University and the QEM collaboration. This first prototype is now being built.
MICROMOUPE aims to push the state of the art both in light and in electron optics. The main goals are:
- Demonstration of cavity enhanced optical detection of single proteins beyond the single-pass shot-noise limit.
- Realization of a wave-front shaping device for electrons.
- Demonstration of a first prototype of a multi-pass transmission electron microscope.