Integration of a local drug delivery system in a micro-fabricated Brain-on-Chip device

Abstract

The process of generating new therapeutics is a complex, highly demanding, and economically challenging procedure. From every 10.000 drug candidates that are introduced to the preclinical phase, only 5 are chosen to be tested for clinical trials. In order to overcome the challenges with current drug screening and toxicity tests, Organ-On-Chip (OOC) systems have been developed. OOCs mainly include a biocompatible membrane or a substrate on which cells or tissue slices are cultured. To perform drug screening tests, the OOC devices need to have a microchannel for drug delivery.
As an example of this class of devices, Brain-On-Chip is presented in this thesis which is developed by TU Delft in collaboration with Leiden University Medical Centre (LUMC). The chip houses a brain slice and electrical activity of the brain tissue is studied before and after cortical spreading depression (CSD) induction. The device consists of a polydimethylsiloxane (PDMS) membrane embedding a microchannel. The PDMS membrane houses the brain tissue and the microchannel delivers chemical needed for CSD induction to a specific region of the tissue.
The main goal of this project is fabrication of the microchannel. To do so, an ultra-thick photoresist (PR) has been characterized which is used for the microchannel fabrication. Unlike most of current OOC fabrications, the Brian-on-chip device presented in this study is fabricated by a clean-room compatible procedure. This may result in a mass-production fabrication and a rapid commercialization. This study aims to validate the Brain-On-Chip by mice brain tissue provided by LUMC. To the best of authors’ knowledge, this is the first attempt to fabricate a clean-room compatible device for CSD induction.