Periodic Reporting for period 1 - NeuroVU (NeuroVU: Real-time Sensing in Microfluidic Models of the Neurovascular Unit)
Reporting period: 2018-06-27 to 2020-06-26
The aim of my research project was to find a holistic solution for integration of biophysical and biochemical sensing capabilities, microfluidics, and neurovascular cells to provide a novel class of organ-on-a-chip (OoC) models of the neurovascular unit (NVU) with advanced real-time sensing capabilities, termed NeuroVU. These systems have the potential to provide unprecedented insight into neurovascular chemistry as well as accelerate pharmaceutical development. The research was carried out at the Kungliga Tekniska Högskolan (KTH) Stockholm in the Department of Micro- and Nanosystems (MST) under the supervision of Professor Anna Herland.
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.