Design of Well and Groove Microchannel Bioreactors for Cell Culture
Design of Well and Groove Microchannel Bioreactors for Cell Culture
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DOI：
10.1002/bit.22153
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发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Levenberg, Shulamit
中科院分区：
文献类型：
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作者：
Korin, Natanel;Bransky, Avishay;Levenberg, Shulamit
微流体生物反应器已被证明对各种细胞应用有价值。使用微孔/凹槽生物反应器，其中微地形特征用于保护敏感细胞免受流体剪切应力的不利影响，是在这些灌注微系统中培养敏感细胞的有前途的方法。然而，与常规平面微通道反应器相比，这样的装置表现出显著不同的流体动力学和传质特性。为了正确地设计和优化这些系统，流体和质量传输的问题，在微型生物反应器中发挥关键作用，应充分解决。本工作是微槽/微孔微通道生物反应器的参数研究。操作条件和设计参数进行了理论研究，通过数值模型。研究了在不同深度的凹槽处获得的复杂流型，并评估了与平面微通道相比的剪切保护因子。为了检查微孔中的剪切保护因子，进行了3D流动模拟，发现微孔具有与凹槽相似的属性。氧质量传输问题，这是耦合到流体力学问题，解决了各种槽的几何形状和几种细胞类型，假设一个定义的剪切应力限制。它表明，通过优化槽的深度，槽生物反应器可以用来有效地最大限度地提高其内培养的细胞的数量或最小化存在于这样的设备中的氧梯度。此外，对于具有高需氧量的敏感细胞（例如，肝细胞）或低剪切耐受性（例如，人胚胎干细胞），结果表明使用凹槽是一种可行的技术，因为在相同的物理条件下，细胞不能在平面微通道中长时间培养。除了理论模型的发现，培养人包皮成纤维细胞的槽（30 μ m深）和良好的生物反应器（35 μ m深）进行了实验研究，在各种流速的介质灌注和比较，细胞培养在常规的平面微通道。结果表明，与平面微通道相比，威尔斯和凹槽能够使最大灌注速率增加一个数量级。总之，该研究表明，适当的设计和使用的微槽/孔生物反应器可能是非常有益的细胞培养试验。
Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro-wells/grooves bioreactors, in which micro-topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro-groove/micro-well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro-wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 mu m depth) and well bioreactors (35 mu m depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays.