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Computers in biology and medicine v.95, 2018년, pp.118 - 128   SCI SCIE SCOPUS
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A web-based application for automated quantification of chemical gradients induced in microfluidic devices

Cóndor, M. (Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain ) ; Rüberg, T. (TailSiT GmbH, Graz, Austria ) ; Borau, C. (Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain ) ; Piles, J. (Max Planck Institute for Intelligent Systems, Tübingen, Germany ) ; García-Aznar, J.M. (Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain ) ;
  • 초록  

    Abstract Advances in microfabrication have allowed the development and popularization of microfluidic devices, which are powerful tools to recreate three-dimensional (3-D) biologically relevant in vitro models. These microenvironments are usually generated by using hydrogels and induced chemical gradients. Going further, computational models enable, after validation, the simulation of such conditions without the necessity of real experiments, thus saving costs and time. In this work we present a web-based application that allows, based on a previous numerical model, the assessment of different chemical gradients induced within a 3-D extracellular matrix. This application enables the estimation of the spatio-temporal chemical distribution inside microfluidic devices, by defining a first set of parameters characterizing the chip geometry, and a second set characterizing the diffusion properties of the hydrogel-based matrix. The simulated chemical concentration profiles generated within a synthetic hydrogel are calculated remotely on a server and returned to the website in less than 3 min, thus offering a quick automatic quantification to any user. To ensure the day-to-day applicability, user requirements were investigated prior to tool development, pre-selecting some of the most common geometries. The tool is freely available online, after user registration, on http://m2be.unizar.es/insilico_cell under the software tab. Four different microfluidic device geometries were defined to study the dependence of the geometrical parameters onto the gradient formation processes. The numerical predictions demonstrate that growth factor diffusion within 3-D matrices strongly depends not only on the physics of diffusion, but also on the geometrical parameters that characterizes these complex devices. Additionally, the effect of the combination of different hydrogels inside a microfluidic device was studied. The automatization of microfluidic device geometries generation provide a powerful tool which facilitates to any user the possibility to automatically create its own microfluidic device, greatly reducing the experimental validation processes and advancing in the understanding of in vitro 3-D cell responses without the necessity of using commercial software or performing real testing experiments. Highlights A web-based application for customizing a microfluidic device.. Automatic estimation of growth factor diffusion through 3-dimensional matrices inside a microfluidic device. Finite element simulations are performed remotely and automatically. The application allows user to explore different microdevices geometries and diffusion conditions.


  • 주제어

    Growth factor transport .   Finite element simulation .   Microfluidic devices .   Web-based application.  

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