Improving safety of electroporation clinical useCVETKOSKA, ALEKSANDRA (Avtor) Reberšek, Matej (Mentor) Electroporationnerve stimulationmuscle contractionclinical electroporatorsstandardizationmedical safety standardsWhen cells are exposed to high-voltage electrical pulses, pores in the cell membrane are formed, leading to a transient increase in plasma membrane permeability. As a result, transmembrane transport of molecules that otherwise cannot pass through the membrane is enabled. This phenomenon, called membrane electroporation is currently taking a fast rise in medicine. We already have some well-established protocols, devices, and promising treatments. However, there are still some challenges that, if solved, may contribute to an even wider application of electroporation in medicine in the future. Therefore, the doctoral dissertation addresses some of the safety issues relevant to the clinical application of electroporation. The topics presented in the thesis relate to minimizing muscle contraction and pain sensation during pulse delivery, as well as safer and easier development and use of clinical electroporators. First, we investigated muscle contraction and pain sensation during delivery of short, high-frequency, bipolar pulses in healthy volunteers. Stimulation of muscles and nerves is a common challenge in electroporation-based therapies during treatments, as it can lead to movement of the electrodes and cause high levels of discomfort during the treatment. Our results confirmed that bipolar high-frequency pulses with a pulse duration of 1 or 2 µs reduce muscle contraction and pain sensation in contrast to the longer monopolar pulses currently used. Secondly, since there is no particular standard or regulation that specifically addresses the safety of medical devices for electroporation, we proposed guidelines for the design of clinical electroporators and defined the minimum requirements for their safe and efficient use that can be incorporated into the particular standards for clinical electroporators in the future. Finally, considering some of the guidelines and requirements for safe design and use of a clinical electroporator we designed and developed a new electroporation device for gene electrotransfer to cells in the skin. The work within the dissertation focused on developing new safety measures for the electroporator to protect the patient from excess output voltage, current or energy.20222022-12-21 09:00:00Doktorsko delo/naloga143444sl