Fabrication Technologies of 3-Dimesional Electrodes for a Heart-on-Chip Application

Abstract

Organs-on-Chips (OoCs) are micro-engineered devices in which small samples of human-organ tissue are cultured on the substrate. A chip is designed in such a way that it can emulate the in-vivo physiological environment for disease modeling and drug screening. OoC technology can be incorporated into the drug development process from early drug discovery to pre-clinical drug screening. This cutting-edge technology can reduce the use of laboratory animals as animal models do not accurately recapitulate the in-vivo physiology and pathology of the human body. Current microfabrication techniques integrate features like microfluidics and micropumps into OoC devices to provide the necessary perfusion. Additionally, it is possible to monitor the behavior of cells or tissue by incorporating sensors into the platform.
Cardiovascular diseases are a leading cause of death worldwide, which calls for an ideal in-vitro screening model for cardiotoxicity. The MUSbit™ device, an OoC developed by Bi/ond, incorporates a 3D muscle microtissue anchored to two pillars designed to align the tissue. The device consists of a microfluidic channel to offer the necessary perfusion to mimic the blood flow through the heart. Bi/ond aims to electrically pace the cardiovascular bundle via the two pillars and record the electrical activity of the cardiac cells. This is achieved by combining an electrode and the pillar. Thus, a 3D electrode in integrated into the platform. Compared to 2-D microelectrode arrays (MEAs), 3D electrodes have a larger surface area, lowering the electrode impedance and increasing the signal-to-noise ratio (SNR).
The existing method of Bi/ond incorporates the electrode underneath the pillar via a cavity ( also known as the basement) in silicon fabricated using Deep Reactive Ion Etching (DRIE). This thesis focused on combining the electrode underneath the pillar by optimizing the critical steps in the fabrication process. The basement provides a form of adhesion for the pillars towards the later stages of the process. Due to the limitations concerning the step coverage of the different layers deposited over the current profile of the cavity, the design was modified. In this project, two main goals were defined and achieved. Firstly, the basement design was optimized by wet etching the silicon using potassium hydroxide (KOH) to obtain a cavity with a slanted sidewall. The photolithography on the layers and the step coverage of the deposited layers on the cavity were investigated. Experiments were performed to observe the effect of the modified basement design on the pillars (without the electrode). Secondly, the feasibility of integrating the electrode underneath the pillar without a basement was assessed. The photomask of the essential layers (except the metal) was designed accordingly. Finally, the influence of the alternative designs on the pillars was tested to verify their viability. Both approaches showed that it is practical to implement the techniques which can be compatible with the process of Bi/ond. The several microfabrication tests presented in this work set a foundation to incorporate the electrodes into the platform, making ground for future studies.