Semi-3-Dimensional 流聚焦微流控装置产生尺寸控制的聚乙二醇二丙烯酸酯液滴
Summary
在这里, 我们提出了一个协议来说明一个半三维 (semi-3D) 流聚焦微流控芯片的形成过程和验证实验。
Abstract
通过微流控装置中的流动聚焦过程, 可以产生均匀和大小可控的聚乙二醇二丙烯酸酯 (PEGDA) 液滴。本文提出了一种用于雾滴形成的三维 (semi-3D) 流聚焦微流控芯片。采用多层软光刻法制作了烷芯片。烷含有表面活性剂作为连续相, PEGDA 与紫外光引发剂是分散相。表面活性剂允许局部表面张力下降, 形成了一个更 cusped 的尖端, 促进破碎成微小的微滴。当分散相的压力恒定时, 液滴的大小随着连续相压力的增大而逐渐减小, 从而使分散相流中断。因此, 通过改变两个进气道的压力比, 可选择性地实现直径从1µm 到80µm 的水滴, 平均变化系数估计在7% 以下。此外, 在光聚合中, 液滴可以通过紫外线照射变成微珠。这种微珠表面的共轭生物分子在生物学和化学领域有许多潜在的应用。
Introduction
液滴基微流控系统具有从纳米到微米直径范围1的高单分散液滴的能力, 在高通量药物发现2中具有很大的潜力, 生物大分子的合成3 、4和诊断测试5。由于小水滴的独特优势, 如表面积大、体积比大、应用少, 微升的样品多, 这项技术在广泛的领域引起了广泛的关注。两种不相容液体的乳化是产生水滴的最典型方法之一。在以前的报告中, 研究人员开发了各种不同的水滴形成几何学, 包括 T 连接, 流动聚焦和共同流动的几何图形。在 T 形连接几何中, 分散相通过垂直通道传递到主通道中, 连续相流6,7。在典型的二维 (2D) 流聚焦8、9几何中, 分散相流从侧面剪切;而对于共流几何10,11, 另一方面, 一毛细管引入分散相流被放置在一个较大的毛细管内的共同流动的几何, 使分散的相流被剪切从所有方向。
液滴尺寸通过调整通道尺寸和流速比来控制, 而由共流或 T 结产生的最小尺寸仅限于数微米。对于流动聚焦液滴形成系统, 通过调整两相和表面活性剂浓度的压力比, 包括滴水状态、喷射机制和尖端流15, 形成三种液滴破裂形式。提示流模式也称为螺纹形成, 并观察从分散相流锥尖端绘制出的细线的外观。先前的研究表明, 在2D 或 semi-3D 流聚焦装置8,12中, 可以产生小于几微米的水滴。然而, 作为一个含有极低浓度 PEGDA 的水溶液作为分散相, PEGDA 颗粒的收缩率大约是光聚合后直径的原水滴的 60%, 而 PEGDA 不稀释作为分散相位导致不稳定的尖端流模式12。界面张力是乳化过程的重要参数, 由于表面活性剂加入到连续相液中会降低, 从而降低液滴尺寸、高频率13、高弯曲尖端, 并防止不稳定14。此外, 当大块表面活性剂浓度比临界胶束浓度高得多时, 在饱和态13中界面张力近似不变, 尖端流态可发生15。
在此基础上, 本文利用多层软光刻技术制备了一种 semi-3D 流聚焦微流控器 PEGDA 液滴生成方法。与典型的2D 流聚焦装置不同, semi-3D 流聚焦装置具有浅分散相通道和深部连续相通道, 使分散相可以在侧边上下剪切。这为流聚焦模式提供了更大的调整范围, 减少了液滴破碎所需的能量和压力。与上一次报告12不同, 分散相是纯 PEGDAcontaining 的光引发剂, 确保 PEGDA 颗粒的收缩率低于 10%16;连续相是烷溶于硅基非离子表面活性剂的高体积浓度的混合物。通过调整两个相的压力比, 产生尺寸可控和均匀的水滴。水滴的直径从80µm 到1µm, 因为液滴分解过程从射流模式到尖端流模式的变化。此外, 在紫外曝光的光聚合过程中合成了 PEGDA 颗粒。易于制造的液滴生成微流控系统将为生物应用提供更多的可能性。
Protocol
Representative Results
Discussion
使用2D 和 semi-3D 微流控装置的流聚焦模式产生的水滴, 以前已经在各种报告8,9,15,19,20, 21。在这些系统中, 不凝固的水溶液被选择为分散的相, 如去离子水8,15,20,<sup class="xre…
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
这项工作得到了深圳基础研究经费的支持 (批准号:JCYJ 20150630170146829, JCYJ20160531195439665 和 JCYJ20160317152359560)。作者要感谢中国科学院深圳先进技术研究院的教授, 为支持。
Materials
| Silicon wafer | Huashi Co., Ltd | ||
| SU-8 2025, 2100 | Microchem Co. | Y111069 | |
| SU-8 developer | Microchem Co. | Y020100 | |
| Chromium mask | Qingyi Precision Mask Making Co., Ltd | ||
| polydimethylsiloxane(PDMS) | Dow Corning | Sylgard 184 | |
| poly(ethylene glycol) diacrylate (PEGDA) | Sigma | 26570-48-9 | |
| 2-hydroxy-40-(2-hydroxyethoxy)-2-methylpropiophenone | TCI | H1361-5G | photoinitiator |
| Hexadecane | Sigma | 544-76- 3 | |
| ABIL EM 90 | CHT | 144243-53-8 | surfactants |
| Rhodamine B | Aladdin | 81-88-9 | fluorescent dye |
| Spin Coater | |||
| Lithography machine | |||
| Automatic ointment agitator | Thinky | ARV-310 | |
| Oven | BluePard | ||
| Optical microscope | OLYMPUS | IX71 | |
| High-speed camera | Hamamatsu, Japan | ORCA-flash | |
| MAESFLO Microfluidic Fluid Control System | FLUIGENT | MFCS-EZ | |
| UV lamp | FUTANSI | 365 nm UV light, 8000 MW/CM2 |
Referencias
- Teh, S. Y., Lin, R., Hung, L. H., Lee, A. P. Droplet microfluidics. Lab on a chip. 8, 198-220 (2008).
- Xiao, Q., et al. Novel multifunctional NaYF4:Er3+,Yb3+/PEGDA hybrid microspheres: NIR-light-activated photopolymerization and drug delivery. Chemical communications. 49, 1527-1529 (2013).
- Pan, M., Kim, M., Blauch, L., Tang, S. K. Y. Surface-functionalizable amphiphilic nanoparticles for pickering emulsions with designer fluid-fluid interfaces. RSC Adv. 6, 39926-39932 (2016).
- Zhang, L., et al. Microfluidic synthesis of rigid nanovesicles for hydrophilic reagents delivery. Angewandte Chemie. 54, 3952-3956 (2015).
- Shembekar, N., Chaipan, C., Utharala, R., Merten, C. A. Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. Lab on a chip. 16, 1314-1331 (2016).
- Soh, G. Y., Yeoh, G. H., Timchenko, V. Numerical investigation on the velocity fields during droplet formation in a microfluidic T-junction. Chemical Engineering Science. 139, 99-108 (2016).
- Chiarello, E., Derzsi, L., Pierno, M., Mistura, G., Piccin, E. Generation of Oil Droplets in a Non-Newtonian Liquid Using a Microfluidic T-Junction. Micromachines. 6, 1825-1835 (2015).
- Moyle, T. M., Walker, L. M., Anna, S. L. Controlling thread formation during tipstreaming through an active feedback control loop. Lab on a chip. 13, 4534-4541 (2013).
- Moon, B. U., Abbasi, N., Jones, S. G., Hwang, D. K., Tsai, S. S. Water-in-Water Droplets by Passive Microfluidic Flow Focusing. Analytical chemistry. 88, 3982-3989 (2016).
- Zhu, P., Tang, X., Wang, L. Droplet generation in co-flow microfluidic channels with vibration. Microfluidics and Nanofluidics. , 20 (2016).
- Kim, S. H., Kim, B. Controlled formation of double-emulsion drops in sudden expansion channels. Journal of colloid and interface science. 415, 26-31 (2014).
- Jeong, W. C., et al. Controlled generation of submicron emulsion droplets via highly stable tip-streaming mode in microfluidic devices. Lab on a chip. 12, 1446-1453 (2012).
- Peng, L., Yang, M., Guo, S. S., Liu, W., Zhao, X. Z. The effect of interfacial tension on droplet formation in flow-focusing microfluidic device. Biomedical microdevices. 13, 559-564 (2011).
- Nunes, J. K., Tsai, S. S., Wan, J., Stone, H. A. Dripping and jetting in microfluidic multiphase flows applied to particle and fiber synthesis. J Phys D Appl Phys. , 46 (2013).
- Anna, S. L., Mayer, H. C. Microscale tipstreaming in a microfluidic flow focusing device. Physics of Fluids. 18, 121512 (2006).
- Liu, H., et al. Microfluidic synthesis of QD-encoded PEGDA microspheres for suspension assay. J. Mater. Chem. B. 4, 482-488 (2016).
- Richardson, W. H. Bayesian-based iterative method of image restoration. Journal of the Optical Society of America. 62, 55-59 (1972).
- Mukhopadhyay, P., Chaudhuri, B. B. A survey of Hough Transform. Pattern Recognition. 48, 993-1010 (2015).
- Ward, T., Faivre, M., Stone, H. A. Drop production and tip-streaming phenomenon in a microfluidic flow-focusing device via an interfacial chemical reaction. Langmuir: the ACS journal of surfaces and colloids. 26, 9233-9239 (2010).
- Anna, S. L., Bontoux, N., Stone, H. A. Formation of dispersions using “flow focusing” in microchannels. Applied Physics Letters. 82, 364 (2003).
- Kim, H., et al. Controlled production of emulsion drops using an electric field in a flow-focusing microfluidic device. Applied Physics Letters. 91, 133106 (2007).
- Dangla, R., Gallaire, F., Baroud, C. N. Microchannel deformations due to solvent-induced PDMS swelling. Lab on a chip. 10, 2972-2978 (2010).
- Chiu, Y. J., et al. Universally applicable three-dimensional hydrodynamic microfluidic flow focusing. Lab on a chip. 13, 1803-1809 (2013).
- Oh, K. W., Lee, K., Ahn, B., Furlani, E. P. Design of pressure-driven microfluidic networks using electric circuit analogy. Lab on a chip. 12, 515-545 (2012).
