From microfluidic technology to organ-on-a-chip platforms : New opportunities to develop physiologically relevant in vitro models

Orateur : Séverine LE GAC (Applied Microfluidics for BioEngineering Research, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Engineering and Technical Medicine, University of Twente, The Netherlands​)

Lab-on-a-chip technology (LOC) or microfluidics has reached a mature state and is currently very popular in the field of life sciences, due to the numerous advantages it offers. Microfluidic devices enable faster, more sensitive and reproducible analysis using lower amounts of reagents. Furthermore, microfluidics lends itself well to the realization of complex and integrated platforms. Originally, microfluidic developments have been driven by the field of bioanalysis. However, applications of LOC have recently been diversified and extended to cellular investigations, for which LOC presents additional advantages such as an in vivo–like and tunable microenvironment, dynamic culture, and a unique capability to couple cell culture, treatment and analysis on one single platform. 
 In my presentation I will particularly discuss two areas of applications of the so-called organ-on-a-chip platforms : assisted reproductive technologies (ART) and cancer research (drug screening). In the field of ART, LOC technology can offer alternative approaches for the in vitro steps of the treatment, remedying thereby currently encountered issues (Le Gac and Nordhoff, Mol. Hum. Reprod., 2017). In our group, we particularly focus on two specific in vitro steps, which are the (i) pre-implantation in vitro culture of the embryos, and (ii) their characterization with the purposes to both monitor their growth and identify embryos with the highest developmental competence before transfer. We have developed a microfluidic platform, which has first been validated on mouse embryos, revealing superior performance of the microfluidic format for embryo in vitro culture, down to the single embryo level (Esteves et al., RSC Adv., 2013). This device was next tested on donated frozen human embryos (Kieslinger et al., Fertil. Steril., 2015). Current work focuses on the integration of an oxygen sensor in the culture chamber to monitor the embryo oxygen consumption, as an indication of their overall metabolism and healthy development (van Rossem et al., Sens. Act. A, 2017 ; Abbas et al., Proc. MicroTAS 2017). In a different project, focusing on in vitro production (IVP) of bovine embryos, we have developed an oviduct-on-a-chip platform, where all steps of the in vitro fertilization (IVF) process and subsequent in vitro embryo culture are implemented, yielding bovine embryos better resembling their in vivo counterparts, compared to IVP bovine embryos produced in traditional dishes (Ferraz et al., Proc. MicroTAS 2017). For drug screening, and to evaluate the penetration and efficiency of nanomedicines, sophisticated and biomimetic in vitro models are required that incorporate essential features of the tumor microenvironment. In that context, we are developing a tumor-on-a-chip device. Our tumor-on-a-chip platforms rely on the use of 3D tumor models (spheroid) (Sridhar et al., Plos One, 2014) prepared from either a mono-culture (breast tumor cells) or co-culture (breast tumor cells and fibroblasts), to yield a model closer to the in vivo situation (Priwitaningrum et al., J. Control. Release, 2016). In our first generation platform, spheroids are trapped in a microfluidic chamber, and this platform has been applied to evaluate the penetration of nanoparticles, employed here as models for nanomedicines, under either static conditions or flow. A second generation platform is under development that will also include a vascular system for the delivery of the drugs/nanomedicines to the tumor site.

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