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

Microfluid Nanofluid (2016) 20:143 DOI 10.1007/s10404-016-1806-2 RESEARCH PAPER A reproducible approach to the assembly of microcapillaries for double emulsion production Mark A. Levenstein1,2 · Lukmaan A. Bawazer2,3 · Ciara S. Mc Nally2 · William J. Marchant2 · Xiuqing Gong2,4 · Fiona C. Meldrum2 · Nikil Kapur1 Received: 7 July 2016 / Accepted: 20 September 2016 / Published online: 7 October 2016 © The Author(s) 2016. This article is published with open access at Springerlink.com Abstract 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. Keywords Droplet microfluidics · Double emulsions · Microcapillaries · Micropipette pulling · Droplet breakup · Dripping-to-jetting transition 1 Introduction Data availability: The data associated with this paper are openly available from the University of Leeds data repository. http://doi. org/10.5518/71. Electronic supplementary material The online version of this article (doi:10.1007/s10404-016-1806-2) contains supplementary material, which is available to authorized users. * Nikil Kapur 1 School of Mechanical Engineering, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK 2 School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK 3 National Institute of Standards and Technology and Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA 94305, USA 4 Present Address: Materials Genome Institute, Shanghai University, 99 Baoshan Road, Shanghai 200444, China 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 13 143 Page 2 of 11 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 and co-workers designed an elegant 3D-printed screw and nut assembly which could be used to align glass capillaries for the controlled generation of oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) double emulsions (Martino et al. 2014). In their device, screws that hold the capillaries for both inner fluid introduction and droplet collection are inserted into nuts fixed to opposite sides of a larger outer capillary of either square or circular cross section. This configuration allows the distance between inner capillaries to be controlled by simply turning the screws. However, while this design offers greater standardization and versatility, devices often fail to generate double emulsions due to the inability to control the alignment of inner capillaries, and thus allow for variations in their shapes. 13 Microfluid Nanofluid (2016) 20:143 In this article, we describe a highly controllable approach to cap (...truncated)