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一种力-电协同驱动的细胞微流控培养腔理论模型

A THEORETICAL MICROFLUIDIC FLOW MODEL FOR THE CELL CULTURE CHAMBER UNDER THE PRESSURE GRADIENT AND ELECTRIC FIELD DRIVEN LOADS

  • 摘要: 细胞培养液在微流控生物反应器中受到外界物理场(如压力梯度或者电场)作用流动而产生流体剪应力,并进一步刺激种子细胞调控其内部基因的表达,从而促进细胞的分化和生长,这个过程在自然生命组织内的微管中亦是如此。考虑到细胞培养微腔隙中液体流动行为很难实验量化测定,理论建模分析是目前可行的研究手段。因此建立了矩形截面的细胞微流控培养腔理论模型,将外部的物理驱动场(压力梯度与电场)与培养腔内液体的流速、切应力和流率联系起来,分别得到了压力梯度驱动(Pressure gradient driven,PGD)、电场驱动(Electric field driven,EFD)及力-电协同驱动(Pressure-electricity synergic driven,P-ESD)三种驱动方式下的液体流动理论模型。结果表明该理论模型与现有的实验结果基本一致,具体地:力-电协同作用下的解答为压力梯度驱动和电场驱动结果的叠加。细胞培养腔内的流体流速、剪应力及流率幅值均正比于外部物理场强幅值,但随着压力梯度驱动载荷频率的增大而减小,随着电场驱动频率的变化不明显。在压力梯度驱动作用下,细胞贴壁处的切应力随着腔高的增大而线性增大,流率则随着腔高的增大而非线性增大,而电场驱动下的结果不受腔高的影响。生理范围内的温度场变化对压力和电场驱动的结果影响不大。另外,在引起细胞响应的流体切应力水平,电场驱动能提供较大的切应力幅值而压力梯度驱动则能提供较大的流率幅值。该理论模型的建立为细胞微流控生物反应器实验系统的设计及参数优化提供理论参考,同时也为力-电刺激细胞生长、分化机理的研究的提供基础。

     

    Abstract: Fluid shear stress (FSS) induced in the microfluidic bioreactor under the driven loads of applied external physical fields (Fluid pressure gradient or Electric filed), which make the cells regulate its genes expression and promote differentiation and growth, so does in the natural tissue microtubule system. It is difficult to experimental quantifications the fluid flowing behavior in the cell culture chamber. The theoretical modeling is thought to be an effective way. In this paper, a theoretical model for microfluidic flow in the rectangle cell culture chamber is developed to link the applied external physical fields (pressure gradient and electrical field) to intraluminal fluid velocity (FV), FSS and fluid flow rate (FFR). The results predict the model solutions are nearly match the others experiment results. Specifically, the solutions under pressure-electricity synergic driven are the superposition of the driven solutions of each pressure gradient and the electric field. FSS, FV and FFR amplitudes in chamber are proportional to the amplitudes of applied external physical fields, but decrease and change little as the frequencies of pressure gradient and electric field grows, respectively. The higher chamber height is, the larger FSS and FFR amplitudes generalized in the pressure gradient driven model, while not obvious change in the electric field driven model. Besides, the results are not influenced when the culture medium temperature varies at the physiological level. At the generalized cell response level, electric field driven model can provides the larger FSS amplitude, while the pressure driven flow model is good at inducing the larger FFR amplitude. The combined pressure-electricity synergic driven model can be used as the theoretical basis to design the experimental cell microfluidic bioreactor system, meanwhile, provides the references to research the mechanism of cell growth and differentiation under the stimulus of (shear)stress and electricity.

     

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