Tumor Treating Fields

Figure 2 shows the numerical EM simulation of a single cell (non-mitotic) and of a dividing cell (mitotic) under TTFields treatment. Here, a simplified cell model is used. The shape of the cell model is spherical and it consists of a cell membrane (capacitance C = 29 pF) and a cytoplasm (ε_r = 80, σ = 1.3 S/m). The capacitive property of the cell membrane shields the interior of the cell from electric fields in low frequency ranges. As the frequency increases, the cell becomes permeable for the electric field. In the case of a mitotic cell, there is a relatively high electric field gradient at the cytokinetic cleavage furrow (CCF) when the electric field is polarized parallel to the mitotic axis. This gradient in electric field is assumed to cause dielectrophoretic forces (s. Figure 3) on cellular compartments which are polarizable or polar, as tubulin dimers.

Furthermore, in the case of the electric field oriented parallel to the mitotic axis, there is also a relatively high field magnitude in the CCF which results in a relatively high specific absorption rate (SAR), probably causing heating within this region. However, the cell model used here is a vast simplification of a real cell structure. By considering other cell compartments as well, further possible mechanisms of action can be worked out and evaluated in terms of significance in the frame of TTFields and cancer treatment.   

Figure 4 shows an equivalent electric circuit model of a dividing cell. The two daughter cells in this model consist of a cell membrane (C_m and R_m) and a cytoplasm (R_i). They are connected by the cleavage furrow (R_cf) and located in an extracellular medium (R_e). The lumped element parameters within this model depend on the electric properties of the respective cell compartments and their size. Thus, this model can be extended to several different cell types and provides the possibility to relate the electric behavior of the cell to the considered compartments. 

Figure 5 shows a schematic view on the experimental setup for in-vitro experiments with cells. Before designing and implementing electronics for this setup, the desired field distribution within the cell culture well has to be defined. In this version (s. Figure 5, left side numerical simulation [2]), two different polarization directions of the electric field vector are enabled by four electrodes. Furthermore, the cell cultivation area is located in a determined area (green circle within cell culture well) in order to irradiate cells under test with an almost homogeneous electric field (with magnitude E_RMS = 100 V/m). The design and implementation of the electronics as well as the programming of the graphical user interface for controlling complement the whole setup.

In cooperation with the Institute of biophysics of Leibniz University of Hannover and the neurologic clinic of the Hanover Medical School various different in-vitro and in-vivo experiments are conducted in the frame of TTFields research. The three cooperation partners complement each other with their expertise on the different major fields important for TTFields research.