Microfluidic generation of acoustically active nanodroplets.
Microfluidic generation of acoustically active nanodroplets.
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DOI：
10.1002/smll.201102418
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发表时间：
2012-06-25
期刊：
影响因子：
13.3
通讯作者：
Dayton, Paul A.
中科院分区：
文献类型：
--
作者：
Martz, Thomas D.;Bardin, David;Sheeran, Paul S.;Lee, Abraham P.;Dayton, Paul A.
托马斯D.放大图片创作者：大卫·巴丁. Shepherd，Abraham P. Lee，and Paul A.来自具有微尺度几何形状的器件的代顿 * 仍然提出了根本性的挑战。以前的微流体方法产生纳米液滴依赖于小卫星液滴（小至100 nm）从微米级液滴群体中固有的低效动态分选，作为单分散亚微米乳化系统的基础。[10-12]为了克服这一限制，我们假设通过调节液滴产生的基本机制以获得更有利的液滴形成机制，[13-15]我们可以产生一种有效的方法来产生作为初级乳液的全氟化碳纳米液滴。我们的团队最近证明了微流控生成微尺度ADV试剂的可行性，以实现对液滴尺寸和均匀活化的精确控制。[7，15]在这项研究中，我们在此之前的工作基础上进行了改进，开发了一种微流体系统，该系统能够通过对先前探索的系统进行两项关键改进来产生直径小至300-400 nm的初级亚微米液滴群体。在最早的研究中，使用注射泵控制所有试剂的输入速率，但注射泵驱动系统固有的机械可变性[16]导致直径下限约为7 μm。[7]通过使用类似于先前研究中使用的自定义压力控制输入来控制分散的全氟戊烷（PFP）相，[16，17]液滴尺寸减小到3-5 μm。[15]在这里，我们证明了所有试剂的压力控制递送（图1a）提供了将微流体装置驱动到尖端流动状态[18]的能力，其具有极低的可变性，使得能够产生亚微米液滴，尽管事实上孔口宽度比液滴本身大一个数量级以上（图1 B）。我们还观察到，通过添加甘油来增加连续相的粘度大大增强了在所使用的高压下在亚微米范围内稳定地驱动液滴产生的能力。相对于卫星液滴分选，如我们所展示的，先进的尖端流允许在亚微米范围内有效地产生液滴，而无需过滤或动态装置内分离。通过精确地改变压力，从而改变连续相和分散相的流速，我们能够用相同的微流体装置产生范围从360 nm到11 μm的窄分散的脂质包封的纳米和微米液滴（表1）。尽管在从本发明产生的器械之间观察到了一些变异性，
Thomas D. Martz, David Bardin, Paul S. Sheeran, Abraham P. Lee, and Paul A. Dayton* from devices with microscale geometry still presents a fundamental challenge. Previous microfluidic approaches to produce nanodroplets have relied on the inherently inefficient dynamic sorting of small satellite droplets (as small as 100 nm) from microscale droplet populations as the basis of a monodisperse sub-micrometer emulsification system.[10–12] To overcome this limitation, we hypothesized that by modulating the basic mechanism of droplet generation to access a more favorable droplet formation regime,[13–15] we could yield an efficient approach for the generation of perfluorocarbon nanodroplets as the primary emulsion. Our group recently demonstrated the feasibility of microfluidic generation of microscale ADV agents to achieve precision control of droplet size and uniform activation.[7, 15] In this study, we advance upon this prior work with the development of a microfluidic system capable of generating populations of primary sub-micrometer droplets with diameters as small as 300–400 nm through two key refinements of the previously explored systems. In the earliest study, syringe pumps were used to control input rates of all reagents, but the mechanical variability inherent to syringe-pump driven systems [16] led to a lower limit of approximately 7 μm in diameter.[7] By controlling the dispersed perfluoropentane (PFP) phase with a custom pressure-controlled input similar to that used in prior studies,[16, 17] droplet sizes were reduced to 3–5 μm.[15] Here, we demonstrate that pressure-controlled delivery of all reagents (Figure 1a) affords the ability to drive the microfluidic device into a tip-streaming regime [18] with extremely low variability—enabling sub-micrometer droplet production despite the fact that the orifice width is over an order of magnitude larger than the droplets themselves (Figure 1 b). We also observed that increasing the viscosity of the continuous phase through the addition of glycerol greatly enhanced the ability to drive droplet production stably in the sub-micrometer regime at the high pressures used. Relative to satellite droplet sorting, advanced tip-streaming, as we demonstrate, allows for efficiency in generating droplets in the sub-micrometer range, without filtration or dynamic indevice separation.By precisely varying the pressures and, consequently, the flow rates of the continuous and dispersed phases, we were able to produce narrowly dispersed lipid-encapsulated nanoand microdroplets ranging from 360 nm to 11 μm with the same microfluidic device (Table 1). Although some variability was observed between devices generated from the
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影响因子：
4.6
作者：
Cubaud, Thomas;Mason, Thomas G.
通讯作者：
Mason, Thomas G.
影响因子：
4.6
作者：
Anna, Shelley L.;Mayer, Hans C.
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影响因子：
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作者：
Ward, Thomas;Faivre, Magalie;Stone, Howard A.
通讯作者：
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影响因子：
2.9
作者：
Martz, Thomas D.;Sheeran, Paul S.;Bardin, David;Lee, Abraham P.;Dayton, Paul A.
通讯作者：
Dayton, Paul A.
影响因子：
4.2
作者：
O'Neill BE;Rapoport N
通讯作者：
Rapoport N