Challenges of Quantitative In-Liquid Ultra-Microscopy in Physiological Conditions

Ultramicroscopy generally exploits some kind of scanning microscopy and, among them, techniques belonging to the Scanning Probe Microscopy family. In those techniques, a probe is raster scanned in the proximity of the sample while recording some probe-sample interaction. When the interaction happens in liquid, and especially in a salty liquid as required in biology, any measurement becomes extremely challenging. Among such techniques, Scanning Microwave Microscopy (SMM) is a technique enabling the characterization of sub-surface structures and the quantitative measurements of electromagnetic parameters, along with spectroscopic capabilities that can support life sciences in the investigation of physiopathological phenomena. The use of SMM however, is still limited to very few laboratories, and is very difficult in salty liquids. In this presentation we will discuss some recent advances, reporting findings about a recent technique, inverted Scanning Microwave Microscopy (iSMM), aimed to broaden the application beyond the current focus on surface physics and semiconductor technology. In this approach, a Copernican paradigm shift is adopted, since the measurement is performed over the sample holder (a transmission line) while the role of the probe is to locally perturb the electromagnetic field during a scan. With reduced requirements about the probe, iSMM is a valid solution to the use of SMM in biology; moreover, an iSMM can be obtained from any existing microscope, paving the way to democratization of SMM use.