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Dielectrophoretic formation of cell aggregates mimicking tumors for in vitro study of electrochemotherapy

Abstract : Electropulsation increases membrane permeability for ions and molecules, including DNA or low-permeant cytotoxic drugs. This mechanism is exploited in Electrochemotherapy (ETC), a treatment that consists in exposing cutaneous or subcutaneous tumors to electric pulses in order to enhance delivery of chemotherapeutic agents such as bleomycin or cisplatin into cancer cells. ECT is currently disseminated in more than 130 cancer centers in Europe and notably applied to the treatment of cutaneous metastases and of tumors located in complex anatomic sites such as head and neck. However, the full development of this therapeutic approach requires proper understanding of electric field impact on biological tissues. While in vitro studies performed on isolated cells provide useful information on how field pulses induce biological membrane permeabilization, more realistic 3D in vitro models are required to mimic the behavior of cells in a tumor or a tissue. 3D models can be used as a convenient approach for optimization of electropulsation protocols, offering a partial alternative to in vivo studies performed on sacrified animals.We present different microfluidic platforms allowing dielectrophoresisassisted formation of cell aggregates of regular size and shape. When specific experimental conditions are met (medium composition, electric field intensity and frequency), negative dielectrophoresis (DEP) allows efficient concentration of cells towards electric field minima and subsequent aggregation. This bottom-up assembly strategy offers several advantages with respect to the targeted application: first, DEP offers precise control of cell spatial organization, which can be adjusted by optimizing electrode design. Then, rapid establishment of cell-cell interactions is allowed thanks to dipoledipole attraction forces between neighboring cells. Lastly, the electrodes used for DEP can also be subsequently used to perform cell aggregate electroporation or characterization by electrorotation or impedance spectroscopy.Three different electrode configurations will be presented. The first one is composed of a planar quadrupolar electrode array fabricated by selectively coating a bipolar electrode array with a thin micropatterned membrane playing the role of an insulating layer. The second aims at further exploiting 3D effects by using thick electrodes made of carbon-doped PDMS. The last one is based on an original approach developed at EPFL, known as “liquid electrodes”. This configuration exploits planar electrodes fabricated on the bottom of deadend chambers placed on each side of a microfluidic channel and acting similarly to thick electrodes embedded in the channel walls.
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Submitted on : Monday, November 7, 2016 - 1:49:55 PM
Last modification on : Friday, May 13, 2022 - 5:34:02 PM


  • HAL Id : hal-01393391, version 1


François Buret, Jonathan Cottet, Marie Frénéa-Robin, Julien Marchalot, Samia Menad, et al.. Dielectrophoretic formation of cell aggregates mimicking tumors for in vitro study of electrochemotherapy. 10th EMF, Apr 2016, Lyon, France. ⟨hal-01393391⟩



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