Characterization, modeling and performance prediction of an electric microfluidic cell Manipulation device

Abstract

Reliable and accurate methods for cell and tissue manipulation are fundamental for a wide range of scientific and commercial endeavors. Progress in this field is quickly reflected in sectors such as pharmaceutics, biotechnology or health care and yields substantial social benefits. AIT Austrian Institute of Technology develops a novel microuidic electrode concept for cell specific lysis and transfection, the so-called "Electrical Cell Manipulation Device" (ECMD). The ECMD produces finely dosed electric fields in the kV/cm range, at voltages of only 10-40 V. These strong electric fields cause a transient formation of pores in the cell membrane (permeabilization), which can be used for cell specific lysis as well as for the transport of active substances or plasmids into the cells, i.e. transfection. The system consists of two plane-parallel titanium electrodes passivated with a high-kappa dielectric. This passivation of thermally oxidized titanium leads to a decoupling of the target area from galvanic currents and frees the biological targets from unwanted electrochemical reactions. Otherwise, these lead to material detachment, bubble formation or changes in the pH-value. This countermeasure prevents the impairment or even destruction of markers or decomposition of samples, as well as unspecific side effects on cells. In order to better understand the system and optimize the process parameters, detailed electrotechnical modeling and quantification is required. The aim of this master's thesis is therefore to characterize the ECMD electrotechnically and to shed light on the essential (bio)physical processes. Furthermore, a model is created which is to provide conclusions on the actual effective internal field strength in dependence on conventional parameters such as voltage amplitude, frequency, waveform etc. In particular, an equivalent circuit diagram is derived which is based on the evaluation of extensive electrical impedance spectroscopy and is then simulated in PSpice®. In the final step, the findings and a comprehensive set of data from biological experiments are combined in the derivation of a statistical model in MATLAB®, which allows for predictions of the lysis rate under specification of all methodological parameters. The application of electric fields to biological samples promises high potential in the fields of biotechnology and medicine. During this thesis, the foundation was laid for a deeper understanding of the ECMD and the transient electric field strength within the electrolyte. These results may initiate further innovation by providing new input for better designs. Furthermore, the compiled prediction model may be extended to incorporate lysis rate predictions for different cell types and thus allow researchers or medical staff to conveniently eliminate arbitrary subsets of cells from a sample suspension.