Integrated Capacitance Sensing for in vitro Characterization of Tumor-Treating Fields

Tumor treating fields (TTFields) are an electric field-based cancer treatment that has inhibitory effects on the tumors’ growth, mainly by arresting cell proliferation or by destroying cells undergoing mitosis. This approach has been approved by the U.S. Food and Drug Administration for treating certain solid tumors. Despite this success, there remains a gap in the scientific knowledge regarding the mechanisms of TTField therapy unlike traditional chemotherapeutic drugs. As such, there are ongoing efforts aimed at studying TTFields in vitro and in animal models in order to elucidate their effects at the molecular level. Due to TTFields’ limited side effects, there are related efforts investigating combinational treatments in case TTFields improve chemotherapy or radiation efficacy.

To support cancer researchers, this dissertation proposes a novel technology platform that will improve current 2D in vitro TTField assay capabilities. Our approach features an integrated platform that combines miniaturized electrodes for TTField pattern generation, a cell culture well for housing cells under study, and a CMOS-integrated capacitance sensor array for measuring cell proliferation in real time. The device forms a lab-on-CMOS microsystem capable of autonomously monitoring cell cultures undergoing TTField treatment for extended durations.

To create a functioning microsystem we needed to address several challenges: firstly com bining TTFields and integrated capacitance sensing while maintaining biocompatibility, secondly engineering the miniaturized electrodes for uniform TTField exposure, and thirdly designing high spatial resolution capacitance pixels while avoiding cross coupling, which entangles measurements. We demonstrated the prototype using MDA-MB-231 (breast cancer) cells under the effect of TTFields and doxorubicin. To confirm the capacitance results we also collected ground truth images using custom techniques that automatically maintain microscope focus in spite of media evaporation.