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)