## 4 The Role of Dielectrophoresis in the Characterization of Skin Tumor Cells  
### Theoretical Background  
The sorting and identification of various target particles, including tumor cells, has undergone an important evolution in recent years, with different methods now available. Depending on the employed external stimuli, there is a wide range of cell manipulation techniques currently in use, including dielectrophoresis (DEP). DEP is a non-invasive manipulation method suitable for measurements at the micro- and nanoscale level, with a great applicability potential in a large variety of bioparticles, including several types of tumor cells [73], CTCs [74], DNA [75], RNA [76] and other small particles, such as exosomes [77]. The applicability of DEP in skin tumor cell characterization relies on both the suitable technical aspects of this method for fragile living cells and the electrochemical properties of the particles. First described by [PERSON] [78] in the early 1950s, this method is currently living a veritable renaissance when thinking of its widely used application in the oncological field. The technique is based on the controlled motion of dielectrically polarized materials suspended in a fluid, which change their spatial and electric load position under a nonuniform electric field. The phenomenon, noticed in both direct and alternating current, is known as positive DEP (pDEP), if the object is displaced toward the stronger electric field [79], or negative DEP (nDEP), when the studied particle is displaced off the field [80]. In order to be a good candidate for DEP, the particle does not need to be electrically charged a priori. Under the presence of the nonuniform electric field gradient, the target particle will act as an electric dipole, so that the electric charges will segregate [81]. In addition to the particle/cell characteristics, DEP is also strongly related to the electrical properties of the suspension media, and the interfacial polarization mechanism expressed mathematically through the Maxwell\(-\)Wagner (MW) equation plays an important role [82]. \[\left\langle F_{DEP}^{\rightarrow}\right\rangle=2\pi R^{3}e_{m}Re\left[ \widetilde{f_{CM}}\right]\
abla\left|E_{rms}^{\rightarrow}\right|^{2}\]  
The use of DEP principles and upgraded microfluidic devices are suitable for cell sorting; theoretically, tumor cells have different responses to healthy ones in different electrical field gradients. As described in the above equation, DEP force depends on cellular factors, such as the electrical properties of the cell's membrane and cytoplasm, and cell's size, but also on extracellular factors, mainly suspense solution conductivity. The role of the Clausius-Mossotti (CM) factor in determining one particle's electrical behavior is detailed in other recent reviews [83,84]. Skin tumor cells broadly imitate the behavior of other tumor cells in the variable electric field. Cancer cells have different morphological properties than normal cells, thereby manifesting different electrical behavior (Figure 2). MM and NMSC cells have irregular shapes and sizes, structurally altered membranes, including folds and ruffles, modifications of the nucleus, and reduced cytoplasm/nucleus ratio. According to previous research [85], membranes' folding factor is a relevant parameter for characterizing the electrical behavior of tumor cells, as larger membrane surface area compared to normal variants alter measurements results by increasing the cell capacitance. Ionic conduction at the cellular level is also relevant when measurements are done in a broader spectrum, cytoplasm resistance decreasing with increased applied voltage as some studies suggest [86]. Cell viability interferes also with DEP results, this feature being particularly of interest when studying cancer cells. According to literature data, the efficacy assessment of antitumor drugs can be done via DEP, as anticancer medication lowers cell viability, thereby decreasing its impedance and most probably deteriorating its membrane and cytoplasm [87].