A reproducible approach to the assembly of microcapillaries for double emulsion production

Microfluidics and Nanofluidics, Oct 2016

Double emulsions attract considerable interest for their utility in applications as diverse as drug delivery, contrast agents, and compartmentalizing analytes for fluorescence-activated cell sorting. Microfluidic platforms offer a particularly elegant approach to generating these structures, but the construction of devices to provide reproducible and stable production of double emulsions remains challenging. PDMS-based systems require specialized surface treatments that are difficult to implement and lack long-term stability, and current glass microcapillary systems, while offering some advantages, lack flexible and reproducible methods for capillary alignment. This article describes a microcapillary-based approach that addresses these key challenges. Our approach utilizes translational stage elements and alignment end caps that are fixed in place once configured, rather than tightly fitting capillaries. This new approach enables alignment to within ±10 µm and allows greater flexibility in choosing the dimensions of the capillary, which contributes to the size and stability of formation of the double emulsion. Importantly, it also allows the user to compensate for the deviations from ideal shape that occur in pulled glass capillaries, which has been a source of failure with previous methods. A detailed description of the critical design and operational parameters that affect double emulsion generation in these capillary microfluidic devices is provided.

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A reproducible approach to the assembly of microcapillaries for double emulsion production

Microfluid Nanofluid A reproducible approach to the assembly of microcapillaries for double emulsion production Mark A. Levenstein 0 1 2 3 Lukmaan A. Bawazer 0 1 2 3 Ciara S. Mc Nally 0 1 2 3 William J. Marchant 0 1 2 3 Xiuqing Gong 0 1 2 3 Fiona C. Meldrum 0 1 2 3 Nikil Kapur 0 1 2 3 Nikil Kapur 0 1 2 3 0 National Institute of Standards and Technology and Department of Bioengineering, Stanford University , 443 Via Ortega, Stanford, CA 94305 , USA 1 School of Chemistry, University of Leeds , Woodhouse Lane, Leeds LS2 9JT , UK 2 School of Mechanical Engineering, University of Leeds , Woodhouse Lane, Leeds LS2 9JT , UK 3 Present Address: Materials Genome Institute, Shanghai University , 99 Baoshan Road, Shanghai 200444 , China Double emulsions attract considerable interest for their utility in applications as diverse as drug delivery, contrast agents, and compartmentalizing analytes for fluorescence-activated cell sorting. Microfluidic platforms offer a particularly elegant approach to generating these structures, but the construction of devices to provide reproducible and stable production of double emulsions remains challenging. PDMS-based systems require specialized surface treatments that are difficult to implement and lack long-term stability, and current glass microcapillary systems, while offering some advantages, lack flexible and reproducible methods for capillary alignment. This article describes a microcapillary-based approach that addresses these key challenges. Our approach utilizes translational stage elements and alignment end caps that are fixed in place once configured, rather than tightly fitting capillaries. Droplet microfluidics; Double emulsions; Microcapillaries; Micropipette pulling; Droplet breakup; Dripping-to-jetting transition 1 Introduction The last two decades have seen great progress in the use of microfluidic technologies to miniaturize biological, chemical, and medical processes. Droplet microfluidics in particular has enabled new modes for cell sorting and analysis (Eun et al. 2011; Mazutis et al. 2013; Zhang et al. 2013) , single molecule immunoassays (Shim et al. 2013) , directing biomolecule evolution (Agresti et al. 2010; Kintses et al. 2012) , and the synthesis of crystals (Lignos et al. 2014; Phillips et al. 2014; Yashina et al. 2012) , contrast agents (Abbaspourrad et al. 2013) , and drug delivery particles (Leon et al. 2014; Xu et al. 2009) —among other advances (Casadevall i Solvas and deMello 2011; Guo et al. 2012; Song et al. 2006; Teh et al. 2008; Theberge et al. 2010) . However, in spite of the great potential of microfluidics (Whitesides 2006) , these devices are still not routinely used by non-specialists, due in part to the demands of device fabrication and the almost inevitable need to trouble-shoot (Whitesides 2013; Yetisen et al. 2013) . Highlighted in a recent push to extend the viability of microfluidic devices for commercial and industrial products (Whitesides 2014) , many groups have sought to provide engineering solutions to the existing technical obstacles. Some of the challenges that have been addressed include the removal and prevention of unwanted air bubbles (Nakayama et al. 2006; Zheng et al. 2010) , improving world-to-chip connection (Fredrickson and Fan 2004; Liu et al. 2003; Yang et al. 2008) , eliminating the need for large external syringe pumps (Tang et al. 2014) , reducing cross contamination (Yang et al. 2008) , elevating the importance of sample collection and preparation (Labuz and Takayama 2014), and overcoming solvent volatility (Gunawan et al. 2014) . In an effort to improve the robustness and functionality of droplet microfluidic platforms, some devices have been constructed from nested glass microcapillaries as an alternative to more conventional materials such as polydimethylsiloxane (PDMS) (Chu et al. 2007; Kim et al. 2007, 2013; Shah et al. 2008; Utada et al. 2005) . These microcapillary devices rely on coaxial alignment of the nested capillaries and can be used to generate both single and multiple emulsion droplets depending on the number and configuration of the fluid flows (Shah et al. 2008) . Double emulsion generation has been achieved by inserting a pulled capillary and an outlet capillary into opposite ends of a larger capillary of square cross section, where selecting inner capillaries of an outer diameter equal to the inner side length of the square capillary provides coaxial alignment (Utada et al. 2005) . As is also true of PDMS-based devices, no standardized fluidic connections exist and syringe needles are often used as improvised inlets and outlets (Kim et al. 2013) . These factors, together with problems with reproducibility, may have contributed to the limited use of such capillary devices in recent years. These challenges have led us, and others (Benson et al. 2013; Chang et al. 2009) , to pursue new routes for reproducible device construction. For instance, deMello (...truncated)


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Mark A. Levenstein, Lukmaan A. Bawazer, Ciara S. Mc Nally, William J. Marchant, Xiuqing Gong, Fiona C. Meldrum, Nikil Kapur. A reproducible approach to the assembly of microcapillaries for double emulsion production, Microfluidics and Nanofluidics, 2016, pp. 143, Volume 20, Issue 10, DOI: 10.1007/s10404-016-1806-2