Category: Micro- and Nanotechnologies
The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell and organ-on-chip applications. Using a thermoset polymeric material, which effectively scavenges dissolved oxygen (DO), microfluidic devices have been fabricated where oxygen was rapidly depleted from the microfluidic chamber. In the work presented here, we specifically used a biocompatible thermoset plastic based on thiol-ene chemistry. It is shown that hypoxic and anaerobic conditions can be rapidly generated (t90 < 6 min) through the inherent scavenging property of the material itself, without any additional chemical additives. By designing the chamber volumes, and thereby changing the surface-to-volume ratio, the oxygen scavenging rate can be adjusted. An important finding is that no saturation of this scavenging effect was observed after constant perfusion for 18 days. Furthermore, steady state DO gradients in a perfused system were generated to study various DO dependent cell responses such as neovascularization. To demonstrate that the scavenging method is well suited for microphysiological disease models, ischemic stroke was mimicked on chip. To this end, blood-brain barrier endothelial cells were cultivated and subsequently exposed to hypoxic conditions. After 4h of oxygen-glucose deprivation cells lose their native morphology and tight-junction formations, as well as over-express permeabilizing factors, similarly as found in vivo. In general, microfluidic chambers with low-oxygen or even anaerobic conditions have a broad applicability, starting from metastatic cell migration studies to anaerobic bacteria cultivation, where control of oxygen concentration and especially oxygen-free environments are essential.
Drago Sticker– Post-doctoral fellow, Department of Pharmacy, University of Copenhagen, Copenhagen, Sjelland, Denmark
Department of Pharmacy, University of Copenhagen
Copenhagen, Sjelland, Denmark
Dr Drago Sticker is a postdoctoral fellow at the University of Copenhagen at the Department of Pharmacy. He was trained as an electrical and biomedical engineer and has a strong interdisciplinary approach in microfluidics combining cell biology with analytics.
Dr Drago Sticker has been awarded for the PhD Scholarship International Graduate School in BioNanoTechnology with the partners Austrian Institute of Technology (AIT, Austria) and the Nanyang Technical University (NTU, Singapore) and has received two poster awards (BioNanoMed conference 2012 and BioNanoTechnology Winterschool 2013). During the PhD studies he mentored several MSc students and currently 5 MSc and 2 PhD students. He was leading the electronics laboratory during his employment at the AIT. Dr Drago Sticker presented his research at 6 international conferences. Currently he is establishing an Organ-on-a-Chip for drug screening research facility at the University of Copenhagen.
Dr Drago Sticker’s research focuses on developing new tools for high throughput screening of drugs using in vitro microphysiological models. The models aim to recreate and mimic the in vivo environment of the cells, tissue or organ under investigation (organ-on-a-chip systems). To enable highly sensitive and reliable assay development, Drago Sticker focuses on the integration of miniaturized sample preparation techniques and miniaturized analytical techniques. Drago Sticker recently developed a novel microfluidic wound healing assay, which was recently published in Analytical Chemistry ranked among top 5% of journals in the field (Sticker et al, Anal Chem, 2017, 89 (4), 2326-2333). Based on this work he also holds an EU patent (EP3231860).