Organ-on-Chips (OOCs) are micro-fabricated devices that combine micro-engineering with in-vitro cell culturing. This combination results in an in-vitro model that mimics the minimal functional unit of a human organ. OOC devices are expected to provide accurate and predictive screening tools that will eventually reduce false negatives and false positives during drug research and development. By exploiting the accuracy of micro-fabrication techniques, multiple features such as micro-channels, micro-fluidics, micro-topologies, micro-pumps, etc., can be embedded in the device to replicate the biological conditions experienced by the cells in an in vivo human tissue. Moreover, it is possible to monitor the behavior and viability of the cells in the model through sensors embedded in the device.
The Cytostretch device, an OOC developed by TU Delft and Philips, consists of a stretchable membrane fabricated on a silicon chip and equipped with microelectrode arrays (MEA) and micro-grooves. This device provides a customizable platform for multiple organ models. The Cytostretch Silicon-based fabrication should guarantee a large-scale fabrication and a rapid commercialization. However, the design choices compromise the electrochemical performance of the Titanium Nitride MEA on the device. In order to solve this problem, this project focused on coating the Cytostretch MEA with PEDOT (Poly (3,4 – Ethylenedioxythiophene)). PEDOT is a conductive polymer, known to exhibit a superior electrochemical performance due to its high porosity. To the best of authors knowledge, this is the first time a PEDOT MEA is embedded in an Organ-on-Chip. Moreover this is the first work reported aiming to produce a stretchable PEDOT MEA at large-scale by following the “polymer-last approach”.
In this project three main issues were addressed and successfully solved. Firstly, the adhesion between the polymer layers composing the Cytostretch device was improved. Secondly, the process and the masks of the Cytostretch were optimized in order to coat the Titanium Nitride MEA with a noble metal (Platinum) in order to facilitate PEDOT deposition. Thirdly, the deposition of PEDOT on top of the Cytostretch electrodes was successfully performed by cyclic voltammetry deposition from an aqueous solution with NaPSS (Sodium-Poly (Styrene Sulfonate)) as the dopant material.
The performance of the novel stretchable PEDOT MEA was assessed with multiple characterization methods such as Electrochemical Impedance Spectroscopy, and Cyclic Voltammetry. Compared to the Titanium Nitride MEA, PEDOT electrodes exhibit an enhanced performance providing an outstanding 94% reduction of the electrochemical impedance at 1 kHz. The new electrodes showed an ohmic behavior over a wider range of frequency. Last but not the least, a significant increase of the total charge delivery capacity (CDC) was obtained during cyclic voltammetry tests. The results reported in this work demonstrate that the electrochemical performance of the Cytostretch can be drastically improved with PEDOT coating. The combination of robust microfabrication and the electrochemical deposition techniques presented in this work is an important step forwards toward the use of the Cytostretch device in pharmacological applications.