Computerized microfluidic cell culture using elastomeric channels and Braille displays
Computerized microfluidic cell culture using elastomeric channels and Braille displays
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DOI：
10.1073/pnas.0404353101
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发表时间：
2004-11-09
影响因子：
11.1
通讯作者：
Takayama, S
中科院分区：
文献类型：
--
作者：
Gu, W;Zhu, XY;Takayama, S
计算机控制的微流控技术将推进许多类型的细胞测定和微尺度组织工程研究，其中时空变化的流体需要被定义。然而，由于集成的可编程泵和阀的可用性有限，这一目标一直难以实现。本文演示了如何刷新盲文显示器，其网格的320个垂直移动的针，可以通过局部变形的弹性硅橡胶内的通道网络集成泵和阀门。所得到的计算机化流体控制能够在以下各项之间切换：（i）流之间的快速且有效的混合，（ii）流之间具有最小混合的多个层流，以及（iii）相同通道架构内的不混溶流体的分段活塞流。使用相同的控制方法精确接种细胞，通过通道重新配置将其划分为不同的亚群，并在灌注下培养每个细胞亚群长达3周。这些可靠的微尺度细胞培养物显示了从C2 C12成肌细胞沿着通道长度的细胞行为梯度，以及未分化成肌细胞的细胞密度和分化模式的差异，两者都可通过含血清培养基的不同流速进行编程。这项技术将使未来的微尺度组织或细胞研究更容易获得，特别是对于高通量，复杂和长期的实验。所描述的微流体致动方法是通用的和计算机可编程的，但简单，包装良好，并且足够便携以供个人使用。
Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.