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A web-based application for automated quantification of chemical gradients induced in microfluidic devices

机译:基于网络的基于Web的自动化量化在微流体装置中诱导的化学梯度

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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 microfiuidic 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.
机译:微型制备的进步允许微流体装置的开发和推广,这是一种强大的工具,用于在体外模型中重建三维(3-D)生物学相关的工具。这些微环境通常通过使用水凝胶和诱导的化学梯度来产生。更进一步地,计算模型在验证之后使得这种条件的模拟而无需实验实验,从而节省成本和时间。在这项工作中,我们介绍了一种基于Web的应用程序,其允许基于先前的数值模型,评估在3-D细胞外基质内诱导的不同化学梯度。该应用能够通过定义表征芯片几何形状的第一组参数和表征基于水凝胶的矩阵的扩散特性的第二组来估计微流体装置内的时空化学分布。在合成水凝胶中产生的模拟化学浓度分布在服务器上远程计算,并在不到3分钟内返回网站,从而为任何用户提供快速的自动量化。为确保日常的适用性,在工具开发之前调查了用户要求,预先选择了一些最常见的几何形状。该工具在用户注册后自由地提供在线,在“软件”选项卡下的http://m2be.unizar.es/insilico_cell上。定义了四种不同的微流体装置几何形状,以研究几何参数对梯度形成过程的依赖性。数值预测表明,3-D矩阵内的生长因子扩散不仅依赖于扩散的物理,而且还取决于表征这些复杂设备的几何参数。另外,研究了不同水凝胶组合在微硫化物装置内的影响。微流体装置几何形状的自动化提供了一种强大的工具,它有利于任何用户可以自动创建自己的微流体装置,大大减少了实验验证过程,并在不需要使用的情况下对体外3-D细胞反应的理解进行了推进商业软件或进行实际测试实验。

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