1. High voltage nanosecond Pulsed Electric Field (nsPEF) electroporation systems
- Author
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Davies, Ilan, Hancock, Christopher, and Palego, Cristiano
- Subjects
Nanoseond Electroporation ,Electroporation ,Pulsed Electric Fields ,Fast Switches ,High Voltages ,Fast Pulses - Abstract
The work presented in this thesis contributes to the field of nanosecond electroporation research and has the potential to help address the global issue of cancer. The work focuses on the design and development of two nanosecond pulsed electric field electroporation systems that support the delivery of nanosecond width pulsed electric fields into biological cell line populations (in-vitro) and bulk tissue (in-vivo). Both the slow and fast electroporation systems have been optimized to deliver high voltages, in excess of 1 kV and nanosecond (10 ns to 300 ns) pulses across 50 Ω load impedance, which is representative of the biological load. The slow nsPEF electroporation system design is based on the fast-switching of Silicon Carbide power MOSFETs connected in a push-pull configuration with the gates driven by suitable optocoupler gate drivers. This work demonstrates that the system can produce a user-selected number of pulsed electric fields from 100 ns to 300 ns duration, with amplitudes in excess of 1 kV, at a user-selected repetition frequency, from 1 Hz to 50 Hz across a 50 Ω load impedances. The fast nsPEF electroporation system design uses a combination of relatively slow charging and rapid discharging of a coaxial transmission line with a stack of avalanche transistors operating as a fast-switching element. The system has been demonstrated to produce a user-selected number of positive, negative, or simultaneously generate positive and negative polarity pulsed electric fields, from 10 ns to 300 ns in duration, with amplitudes in excess of 1 kV, at user-selected repetition frequencies across a 50 Ω load impedance. The nanosecond pulsed electric field electroporation systems developed in this work have the potential for use in cell manipulation and control of cell physiology. Unlike current radiofrequency, microwave and conventional cancer treatment methods of chemotherapy and radiotherapy, the nanosecond pulsed electric field generated provides the possibility to non-thermally irreversibly electroporate cells suspended in a fluid and bulk tissue. The in-vitro and in-vivo results obtained from a biological cell line and bulk tissue indicate the nanosecond pulsed electric fields can be used to open cell membranes and allow materials, such as chemotherapy drugs, to be locally introduced into the cells. It has also been shown that cells can be non-thermally ablated without damage to collagen. In this instance porcine liver was used as a representative bulk tissue model. This work led to the filing of multiple patent applications, thirteen conference papers and one journal paper in the IEEE European Microwave Conference (EuMC). This work has contributed to the field of nanosecond electroporation research and the development of nanosecond electroporation as an alternative non-thermal energy-based therapeutic for cancer treatment.
- Published
- 2023