One part of the project was the development and characterization of novel fabrication approaches for OoCs. Current technology largely relies on silicones or thermoplastics, which are poorly suited to systems integration (particularly sensors, but also other components with disparate materials). The main Thrust was focused on off-stoichiometry thiol-ene-epoxy (OSTE+) which has very favorable properties for this type of OoC integration, though demonstrated applications had been very limited. I established that the material is compatible with highly sensitive cell culture such as human induced pluripotent stem cells (hiPSCs). I optimized its fabrication and assembly processes to be able to produce tens to hundreds of near-identical devices with relative ease. I moreover studied the ad- and absorption of small molecules, including fluorescent dyes and neuropsychopharmaca.
Another research direction arising from materials considerations was focused on adhesive tape. The standard OoC processes (as well as my OSTE+ process) are prohibitively expensive in terms of needed equipment and expertise for researchers outside of high-resource environments. I developed a process for fabricating a tissue barrier OoC based on simple stacking of cut-out double-sided tape and off-the-shelf parts, requiring only around one hundred euros initial equipment investment. I demonstrated biological functionality with a metabolic study of the effects of chili pepper capsaicinoids.
Using the OSTE+ approach, I demonstrated one of the first isogenic (i.e. from the same donor) hiPSC-based NVU OoC. By relying on isogenic hiPSCs, the NVU model can be highly specific not just to a disorder, but to an individual patient. With the integrated sensors, I was able to show unprecedented temporal resolution in monitoring barrier integrity. To demonstrate, I specifically focused on nitrosative stress and inflammation, as well as how the NVU can be protected by pharmaceutical intervention.
I furthermore pursued multiple research avenues to optimize or eliminate the plastic membranes that support cell growth in the aforementioned OoCs. In this realm, I showcased a new laser photoablation process to create ultra-thin, ultra-porous membranes from commercial plastic films. I characterized biomimetic hydrogel-based membranes created from bio-active silk proteins or nanofibrillar cellulose. Last but not least, I established a 3D hydrogel-based OoC with in-vivo-like tubular geometry that retains the monitoring capabilities of planar membrane-based approaches.
The research conducted within this project has been presented at a number of national and international conferences. Three peer-reviewed journal articles have already been published, with the most widely appealing featured in a university-wide press release. I moreover participated in Falling Walls Lab to garner more public attention. Dissemination activities will continue past the project end date, in particular with multiple journal manuscripts close to completion. Outreach opportunities are sadly somewhat curtailed this year, but will nonetheless continue to be pursued.
