Electric control of droplets in microfluidic devices
Electric control of droplets in microfluidic devices
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DOI：
10.1002/anie.200503540
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Weitz, DA
中科院分区：
文献类型：
--
作者：
Link, DR;Grasland-Mongrain, E;Weitz, DA
微流控设备对流体的精确操纵使许多基于流体的技术发生了革命性变化，并使使用微量试剂的高通量反应堆的开发成为可能。然而，随着这些反应堆规模的缩小，表面吸附和扩散造成的污染效应限制了可以使用的最小数量。试剂在不相容的载体流体中的液滴中的限制克服了这些限制，但需要新的流体处理技术。我们提出了一种基于带电液滴和电场的平台技术，该技术能够实现电寻址液滴的产生、高效的液滴合并、精确的液滴破碎和充电以及可控的液滴分选。这是高通量液滴微流控反应器的基本使能技术。小通道网络是用于精确操纵少量流体的灵活平台。[1，2]这种微流控装置的使用在很大程度上取决于使能技术，如微流控蠕动泵、电动泵、[4，5]和介电泵或电润湿驱动的[6]流；这些技术可构成组装流体处理模块的基本构件。[7]这些模块可用于执行各种关键任务，包括精确测量流体的等量、流体流动的组合以及多个流体成分的混合。将这些模块组装成完整的系统为构建微流控设备提供了一种方便和坚固的方法。它们有无数的用途；例如，高通量筛选，[8]化学相图的探索，生物分子的分析，[9-11]单细胞分析，[12-17]和蛋白质结晶的组合方法[18]都可以用最少的试剂进行。然而，几乎所有的微流控装置都是基于流体的流动；由于扩散和表面吸附的污染效应，这对可有效使用的最小试剂体积设置了限制。随着小体积尺寸的减小，扩散成为混合的主要机制，导致反应物的分散。此外，反应物的表面吸附虽然很小，但在低浓度和小体积时可能是非常有害的。因此，目前的微流控技术不能可靠地用于涉及微量试剂的应用--例如，低至单个分子级别的生物分析不容易进行。克服这些限制的一种方法是在不相容的载体流体中使用水滴；[19]这些液滴提供了一个定义明确、被封装的微环境，消除了扩散或表面相互作用引起的交叉污染或浓度变化。液滴提供了理想的微胶囊，可以分离反应材料、细胞或小颗粒，以供进一步操作和研究。此外，通过使液滴小到1飞升，可以研究单个生物分子的反应。然而，到目前为止，几乎所有用于微流控系统的使能技术都集中在单相流体流动上，几乎没有相应的有效手段来操纵液滴。特别是，微流控几何形状的试剂的操纵、混合和组合对液滴来说比对单流要困难得多[19，20]，特别是当液滴用
The precision manipulation of streams of fluids with microfluidic devices is revolutionizing many fluid-based technologies and enabling the development of high-throughput reactors that use minute quantities of reagents. However, as the scale of these reactors shrinks, contamination effects due to surface adsorption and diffusion limit the smallest quantities that can be used. The confinement of reagents in droplets in an immiscible carrier fluid overcomes these limitations, but demands new fluid-handling technology. We present a platform technology based on charged droplets and electric fields that enables electrically addressable droplet generation, highly efficient droplet coalescence, precision droplet breaking and recharging, and controllable droplet sorting. This is an essential enabling technology for a high-throughput droplet microfluidic reactor.Networks of small channels are a flexible platform for the precision manipulation of small amounts of fluids.[1, 2] The utility of such microfluidic devices depends critically on enabling technologies such as the microfluidic peristaltic pump,[3] electrokinetic pumping,[4, 5] and dielectrophoreticpump or electrowetting-driven [6] flow; these technologies can form the essential building blocks for the assembly of fluidhandling modules.[7] These modules can be used to perform a variety of key tasks including the measurement of precise aliquots of fluids, the combination of fluid streams, and the mixing of multiple fluid components. The assembly of such modules into complete systems provides a convenient and robust way to construct microfluidic devices. These have myriad uses; for example, high-throughput screening,[8] the exploration of chemical phase diagrams, assays of biological molecules,[9–11] single-cell analysis,[12–17] and combinatorial approaches to protein crystallization [18] can all be performed with only minimal consumption of reagents. However, virtually all microfluidic devices are based on flows of streams of fluids; this sets a limit on the smallest volume of reagent that can be used effectively because of the contaminating effects of diffusion and surface adsorption. As the dimensions of small volumes are decreased, diffusion becomes the dominant mechanism for mixing leading to dispersion of reactants. Moreover, surface adsorption of reactants, although small, can be highly detrimental at low concentrations and small volumes. As a result current microfluidic technologies cannot be reliably used for applications involving minute quantities of reagent—for example, bioassays at levels down to the single molecule are not easily performed. An approach that overcomes these limitations is the use of aqueous droplets in an immiscible carrier fluid;[19] these droplets provide a well-defined, encapsulated microenvironment that eliminates cross-contamination or changes in concentration caused by diffusion or surface interactions. Droplets provide the ideal microcapsule that can isolate reactive materials, cells, or small particles for further manipulation and study. Moreover, by making droplets as small as one femtoliter, reactions of single biomolecules can be investigated. However, essentially all enabling technology for microfluidic systems developed thus far has focused on single-phase fluid flow, and there are few corresponding, active means to manipulate droplets. In particular, manipulating, mixing, and combining reagents in microfluidic geometries is much more difficult for droplets than for single streams,[19, 20] especially when the droplets are stabilized with