Microdevices for Investigating Pulsed Electric Fields-Mediated Therapies at Cellular and Tissue Level

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Virginia Tech

Recent attempts to investigate living systems from a biophysical point of view has opened new windows for development of new diagnostic methods and therapies. Pulsed electric fields (PEFs) are a new class of therapies that take advantage of biophysical properties and have proven to be effective in drug delivery and treating several disorders including tumors. While animal models are commonly being used for development of new therapies, the high cost and complexity of these models along with the difficulties to control the electric field in the animal tissue are some of the obstacles toward the development of PEFs-based therapies. Microengineered models of organs or Organs-on-Chip have been recently introduced to overcome the hurdles of animal models and provide a flexible and cost-effective platform for early investigation of a variety of new therapies. In this study microfluidic platforms with integrated micro-sensors were designed, fabricated and employed to study the consequences of PEFs at the cellular level. These platforms were specifically used to study the effects of PEFs on the permeabilization of the blood-brain barrier for enhanced drug delivery to the brain. Different techniques such as fluorescent microscopy and electrical impedance spectroscopy were used to monitor the response of the cell monolayers under investigation. Irreversible electroporation is a new focal ablation therapy based on PEFs that has enabled ablation of tumors in a non-thermal, minimally invasive procedure. Despite promising achievements and treatment of more than 5500 human patients by this technique, real-time monitoring of the treatment progress in terms of the size of the ablated region is still needed. To address that necessity we have developed micro-sensor arrays that can be implemented on the ablation probe and give real-time feedback about the size of the ablated region by measuring the electrical impedance spectrum of the tissue.

Blood-brain barrier, Electroporation, Microfluidics, Drug delivery, Electrical impedance spectroscopy