A novel in vitro device to deliver induced electromagnetic fields to cell and tissue cultures

Rea Ravin; Teddy X. Cai; Randall H. Pursley; Marcial Garmendia-Cedillos; Tom Pohida; Raisa Z. Freidlin; Herui Wang; Zhengping Zhuang; Amber J. Giles; Nathan H. Williamson; Mark R. Gilbert; Peter J. Basser

doi:10.1016/j.bpj.2020.11.002

arXiv · 2011.09698

A novel in vitro device to deliver induced electromagnetic fields to cell and tissue cultures

Rea Ravin·Teddy X. Cai·Randall H. Pursley·Marcial Garmendia-Cedillos·Tom Pohida·Raisa Z. Freidlin·Herui Wang·Zhengping Zhuang·Amber J. Giles·Nathan H. Williamson·Mark R. Gilbert·Peter J. Basser

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Abstract

We have developed a novel in vitro instrument that can deliver intermediate frequency (100 - 400 kHz), moderate intensity (up to and exceeding 6.5 V/cm pk-pk) electric fields (EFs) to cell and tissue cultures generated using induced electromagnetic fields (EMFs) in a solenoid coil. A major application of these EFs is as an emerging cancer treatment modality. In vitro studies by Novocure Ltd. reported that intermediate frequency (100 - 300 kHz), low amplitude (1 - 3 V/cm) EFs, which they called "Tumor Treating Fields" (TTFields), had an anti-mitotic effect on glioblastoma multiforme (GBM) cells. The effect was found to increase with increasing EF amplitude. Despite continued theoretical, preclinical, and clinical study, the mechanism of action remains incompletely understood. Previous in vitro studies of "TTFields" have used attached, capacitively coupled electrodes to deliver alternating EFs to cell and tissue cultures. This contacting delivery method suffers from a poorly characterized EF profile and conductive heating that limits the duration and amplitude of the applied EFs. In contrast, our device delivers EFs with a well-characterized radial profile in a non-contacting manner, eliminating conductive heating and enabling thermally regulated EF delivery. To test and demonstrate our system, we generated continuous 200 kHz EMF with an EF amplitude profile spanning 0 - 6.5 V/cm pk-pk and applied them to human thyroid cell cultures for 72 hours. We observed moderate reduction in cell density (< 10%) at low EF amplitudes (< 4 V/cm) and a greater reduction in cell density of up to 25% at higher amplitudes (4 - 6.5 V/cm). Our device can be extended to other EF frequency and amplitude regimes. Future studies with this device should contribute to the ongoing debate about the efficacy and mechanism(s) of action of "TTFields" by better isolating the effects of EFs.

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Rea Ravin, Teddy X. Cai, Randall H. Pursley, Marcial Garmendia-Cedillos, Tom Pohida, Raisa Z. Freidlin, Herui Wang, Zhengping Zhuang, Amber J. Giles, Nathan H. Williamson, Mark R. Gilbert, Peter J. Basser. 2020-11-19. A novel in vitro device to deliver induced electromagnetic fields to cell and tissue cultures. https://doi.org/10.1016/j.bpj.2020.11.002

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