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微流控装置中葡萄糖的时空分布模式取决于介质的孔隙率和渗透率:有限元研究。

Spatiotemporal pattern of glucose in a microfluidic device depend on the porosity and permeability of the medium: A finite element study.

机构信息

Mechanical Projects Laboratory - LPM, School of Mechanical Engineering - UFU, Uberlandia, Brazil; Institute of Science and Technology - UFVJM, Diamantina, Brazil.

Institute of Science and Technology - UFVJM, Diamantina, Brazil.

出版信息

Comput Methods Programs Biomed. 2019 Dec;182:105039. doi: 10.1016/j.cmpb.2019.105039. Epub 2019 Aug 17.

DOI:10.1016/j.cmpb.2019.105039
PMID:31472476
Abstract

BACKGROUND

Glucose plays an important role as a source of nutrients and influence cellular processes such as differentiation, proliferation and migration. In vitro models based on microfluidic devices represent an alternative to study several biological processes in a more reproducible and controllable method compared to in vivo models. Glucose concentration across a microfluidic chip and its behavior in experimental conditions is not completely understood.

OBJECTIVE

This paper investigated the spatiotemporal distribution of glucose across the hydrogel inside a microfluidic chip. The influence of different parameters, boundary and initial conditions of experiments on glucose concentration was studied.

METHODS

A finite element model using a two dimensional geometry was developed. With this model, patterns of glucose concentration were investigated for different combinations of flow rate of culture medium, permeability and porosity of the medium. Patterns were also studied for two hydrogels made of collagen type I and fibrin with different initial and boundary conditions for pressure and glucose concentration.

RESULTS

Porosity influenced significantly on the chemical gradients generated when interstitial fluid flow was null or neglectable. A difference in concentration lower than 15% was obtained at the input of microchamber and after 90 min, when porosity changed from 0.5 to 0.99. In addition, no significant effects of modifications in permeability were observed. Regarding the collagen and fibrin matrices, in the presence of a pressure gradient of 40 Pa, the permeability significantly influenced on the concentration gradients generated.

CONCLUSIONS

Porosity influences importantly on patterns when diffusion is the main transport mechanism. Permeability is the most influencing parameter when a fluid flow is present. Common insertion rates of culture medium does not significantly modify the patterns of glucose inside the chips. Thus, new experiments must consider the impact of such parameters on the distribution and the time span that nutrients occupy the medium. To better contribute with experimental trials, other studies involving cell-cell and cell-extracellular matrix interactions, and different chip geometries should be developed. The results of the present work could assist to develop specific systems for experimentation, to design new experiments and to improve the analysis of the obtained results.

摘要

背景

葡萄糖作为营养物质的来源,对细胞的分化、增殖和迁移等过程发挥着重要作用。与体内模型相比,基于微流控器件的体外模型是一种更为重现和可控的方法,可用于研究多种生物学过程。但人们对于微流控芯片中葡萄糖的浓度分布及其在实验条件下的行为还没有完全了解。

目的

本研究旨在探究微流控芯片内水凝胶中的葡萄糖时空分布。研究了不同参数、边界和实验初始条件对葡萄糖浓度的影响。

方法

建立了一个使用二维几何形状的有限元模型。利用该模型,研究了不同培养基流量、介质渗透率和孔隙率组合下的葡萄糖浓度模式。还研究了两种由 I 型胶原蛋白和纤维蛋白制成的水凝胶,它们在压力和葡萄糖浓度的初始和边界条件方面存在差异。

结果

当间质液流动为零或可忽略不计时,孔隙率对产生的化学梯度有显著影响。当孔隙率从 0.5 变为 0.99 时,在微腔入口处和 90 分钟后,浓度差异低于 15%。此外,渗透率的变化没有明显影响。对于胶原蛋白和纤维蛋白基质,在 40 Pa 的压力梯度下,渗透性对产生的浓度梯度有显著影响。

结论

当扩散是主要的传输机制时,孔隙率对模式有重要影响。当存在流体流动时,渗透性是最具影响力的参数。培养基的常规插入率不会显著改变芯片内葡萄糖的分布模式。因此,新的实验必须考虑这些参数对营养物质分布和占据介质时间跨度的影响。为了更好地为实验试验做出贡献,还应开展涉及细胞-细胞和细胞-细胞外基质相互作用以及不同芯片几何形状的其他研究。本工作的结果可以协助开发特定的实验系统,设计新的实验,并改善对所获得结果的分析。

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