Near Field Scanning Microwave Microscopy in Biology for Cellular and Subcellular Characterization

Near field Scanning Microwave Microscopy (SMM) is emerging as an important complementary technique for the experimental characterization of biological samples, down to nano-scale. Working with cells or biological tissues poses several problems, especially if samples are to be scanned in-vivo in physiological environment (liquid buffer). Working with relaxed operating conditions, like scanning dried samples (or samples while drying), could be less difficult, but still highly challenging. For instance, whenever using STM-assisted SMM there may be conflicting constraints, like the use of low bias to avoid electrochemical reactions and to avoid amplifier saturation from ionic currents, which is in contrast with the need of high bias to allow the detection of non-conducting surfaces. From a more general point of view, the present work proposes a wide discussion on some of the main challenges of the SMM technique, in particular: achieving quantitative measurements during imaging, looking “underneath” the surface (subsurface probing), and imaging transient and dynamical phenomena. Both STM- and AFM-based implementations of microwave microscopy are considered for comparison. The calibration issue, a central point of any SMM measurement, is also addressed, by considering the capability of the system to provide quantitative data about the surface electrical features, and by trying to disentangle the sample information from topography or from unwanted electromagnetic signals – reflected back to the probe tip. In this context, a possible approach for time-domain calibration is described, starting from a broadband measurement which allows spectroscopic analysis and Time-Domain Reflectometry (TDR). Several examples about microwave scanning of biological scans are reported.