Microwave Sensors for the Dielectric Characterization of Biological Cells
As extensively discussed in the relevant literature, microwave cell characterization offers the distinct advantage of being non-destructive and label-free. This is expected to open-up new opportunities in biomedical and biotechnological applications. Measurements on both cell suspensions and single cells in microfluidic channels have been reported and differences in the (electromagnetic) response of healthy and dead cells have been documented. However, so far only little effort has been spent at single-cell level in determining a unique signature, like the permittivity. The influence of the cell size and of its inhomogeneity has not been addressed at all. We aim at closing this gap by developing (miniaturized) high-frequency sensors and characterization methods with which the broadband dielectric properties of single cells can be determined independently of their size. It shall be taken into account that cells are irregularly shaped, squeezable, and possibly inhomogeneous. To reach these goals we propose two complementary approaches. The first one shall rely on a planar sensor probing only a part of the cell, but not the surrounding culture medium. For a comprehensive examination, the cell shall be probed from different directions/angles. For this, it is to be rotated, which shall be done electrically by means of electrorotation. This will be combined with dielectrophoresis to yield a very flexible means to manipulate and position the cells.In the second approach, the cell shall be probed with a homogeneous field. For this, the sensor shall be a parallel plate capacitor provided with properly biased guard electrodes, a well-proven way to mitigate the negative effect of fringing fields at low frequencies. The sensor shall thus illuminate the whole cell – or at least significant portions of it. A simple three way single cell mechanical trap is to be integrated in this approach.In both approaches, the broadband permittivity shall be extracted by means of measurement-based equivalent circuit models. For this, a simple calibration procedure, which has been developed at our institute, shall be adapted. A (statistical) comparison of the results from the two approaches is expected to provide clues regarding their meaningfulness. This will help classifying, interpreting, and understanding the results obtained with cells of different pathological state.The ultimate objective of this project phase is to find a permittivity footprint for different commercially available cell lines and to differentiate, as far as possible, between different pathological states of cells, which could be healthy, dead, cancerous, or affected by electroporation. In a possible second project phase, the measurements and methods shall be applied to study primary cells.