ID: 2226

• Title:
  Application of Bioelectronic- electroporation Lesion Ablation to target Temporal lobe Epilepsy
  
  Authors:
  

  Matta, Rita- Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France
  Kaszas, Attila- Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France 
  Baca, Martin- Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France
  Moreau, David- Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France
  O'Connor, Rodney- Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France

  
  
  Abstract:
  INTRODUCTION
  
  The primary method of treatment for patients suffering from drug-resistant focal-onset epilepsy is resective surgery, which could impact neurocognitive function [1]. Irreversible electroporation (IRE) is a proven method of focal ablation that circumvents the primary concerns regarding focal RF and laser ablation [2]. Moreover, flexible transparent electrodes are crucial in biomedical applications, for biocompatibility, reduced mechanical stress, better interfacing with soft tissues, optical accessibility, and minimal signal distortion. We propose a flexible implant incorporating organic electrodes [3] that are initially micro-fabricated in a controlled clean room environment. To simplify the process,reduce waste, and enhance efficiency, we employ advanced printing techniques for the subsequent production of the electrodes, coupled with the utilization of microneedles to facilitate deeper brain stimulation. Through the implementation of these diverse probes, our primary objective is to employ IRE as a means of achieving focal ablation of epilepsy, while simultaneously mitigating potential damage to the surrounding brain tissue.
  
  
  
  METHODS
  
  For the devices made in cleanroom environment, Parylene C was deposited on a clean glass slide via chemical vapor deposition process. Gold electrodes and connection leads were patterned through the use of classical photolithography techniques, and deposited through thermal evaporation. After the deposition of a second, insulating layer of Parylene C, electrodes active sites and contacts were opened with the use of reactive ion etching. Finally, PEDOT:PSS, a conductive polymer with both ionic and electronic conductivities, was deposited on the top of the electrodes.
  
  In the second method, the entire probe was printed using a Fujifilm DMP 2831 inkjet printer, utilizing conductive and dielectric ink formulations. This approach ensured a reproducible, efficient, and cost-effective process for printing the probe. The microneedles were fabricated utilizing a hybrid technique combining the capabilities of a Phrozen Sonic Mini 8K printer and PaC coating to achieve optimal results.
  
  
  
  Subsequently, the devices will be interconnected using a Zero Insertion Force (ZIF) cable and a specialized micro packaging technique, forming a robust packaging solution with high barrier properties to effectively withstand light, liquid, and heat.
  
  
  
  RESULTS AND FIGURES
  
  Two-photon calcium imaging was used in anesthetized mice in which flexible bioelectric devices have been implanted. IRE protocols were applied and calcium signals were measured. As a result, Two different signals were observed: within 200um in the vicinity of the electrodes a strong and fast calcium signal was triggered, and intracellular calcium ion concentration remained high, suggesting cells were damaged. Beyond those 200 um, transient calcium signals were observed with a small delay, with return to baseline, suggesting no damage occurred.
  
  
  
  
  
  Keywords:
  epilepsy, printable devices, flexible devices, irreversible electroporation, ablation
  
  Refs:
  [1] P. Kwan and M. Brodie, Early identification of refractory epilepsy, The New England Journal of Medicine, vol. 3, no. 342, pp. 314-319, 2000. [2] M. Howenstein and K. Sato, Complications of Radiofrequency Ablation of Hepatic, Pulmonary, and Renal Neoplasms, Semin intervent Radiol, vol. 3, no. 27, pp. 285-295, 2010. [3] C. Proctor, A. Kaszas, I. Del Agua, A.-M. Pappa, C. Bernard, A. Williamson and G. Malliaras, Electrophoretic drug delivery for seizure control, Science Advances, vol. 4, 2018.
  
  Topic 1:
  5. Exposure devices and methods
  
  Topic 2:
  12. Biomedical applications