|Review written by Noémi Thomazo, PhD
Microfluidics Research Engineer
A Short Review on Monodisperse double emulsion in microfluidic chips
1. Introduction to monodisperse double emulsion production in microfluidic chips
Multiple emulsions (monodisperse double emulsions for example) are promising materials for industrial fields like cosmetics, pharmaceutics or food. These emulsions in an emulsion can be used to encapsulate fragile compounds (drugs, vitamins, aromas…), to protect them during storage and eventually to release the encapsulated compound on demand at the suitable time and place. Typically, double emulsions are made in two steps with two surfactants. For example, to create a water-in-oil-in-water emulsion, water is first emulsified with an oil phase containing hydrophobic surfactant, and re-emulsified in a second step with a water phase containing a hydrophilic surfactant. Double emulsions are thus complex to obtain. The second step, in particular, needs to be handled with care in order to preserve the primary emulsion. In addition, emulsions produced with this technique are polydisperse, which is not desirable for the industry and affects the stability of the double emulsions. Microfluidics can address some of these drawbacks and allow the formation of perfectly monodisperse double emulsions in a controlled way.
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2. Double emulsions in a microfluidic chip: which geometry?
There are three major geometries to generate droplets with microfluidics:
These three techniques have been adapted for the formation of doubles emulsions.
The simplest and most widely studied geometry is the succession of two cross junctions (flow-focusing)1–4. This geometry is compatible with soft-lithography techniques and can be easily adapted to the formation of higher order multiple emulsions. At the first junction the internal droplets are formed and they are encapsulated into the external droplets at the second junction. Another flow-focusing geometry has been developed by Weitz’s team5 using glass capillaries. This device is effective to generate double emulsions but it is also very difficult to assemble.
The other geometries have been also used to produce double emulsions, for example co-flowing with the work of Panizza6, or double T-junctions geometry with Okushima7.
3. Double emulsion in a microfluidic chip: how to combine opposite wettabilities on the same chip?
To be able to generate a droplet in a microfluidic chip, the wettability of the walls is a crucial parameter. It is indeed required that the droplets cannot wet the walls, otherwise they would be broken: to create oil-in-water droplets, the walls of the channels need to be hydrophilic.
The formation of a double emulsion in a microfluidic chip is thus quite complex, since two opposite wettabilities need to be combined on the same device.
Wettability of PDMS for microfluidics
Figure 1: Generation of double emulsion in microfluidics with different geometries: a) two successive cross-junctions, b) co-flowing (from Panizza et al. ), c) flow-focusing (Utada et al. )
PDMS, the most widely used material for microfluidics, is intrinsically a hydrophobic material. When exposed to oxygen ions generated by plasma cleaner, the surface is oxidized, and the methyl groups of the surface are replaced by OH moieties, making it hydrophilic8. However this effect only lasts a couple of hours, because the uncured oligomers contained in the bulk material will migrate to the surface over time9. The exposure to plasma is also a way of activating PDMS surface: the -OH moieties are indeed able to create covalent bonds with various silanes for example. This can be used to tune the wettability of the channels but it is difficult to coat only a specific part of the microfluidic chip in order to produce double emulsions.
Several methods have been developed by researchers to combine hydrophilic and hydrophobic parts on the same chip and enable the formation of double emulsions. Most of them are based on local surface treatment in the part that needs to be kept hydrophobic.
Surface-coating based treatments to make double emulsions
Hu et al.10, or Weitz’s team1,11 coat the channels of the chip with a hydrophilic polymer. First, they adsorb a photoinitiator on the walls, and then they inject an acrylic acid solution inside the channels and initiate the polymerization by exposure to UV light. Hu et al. worked with benzophenone whereas Weitz worked with silanes. Only the channels that need to become hydrophilic are coated thanks to the use of a mask during UV exposure.
These techniques are very efficient, but also time consuming. Moreover, the injection of liquids into the microfluidics chips previously to the formation of double emulsions increase the risk of obstructing the channels.
Bauer et al.3 developed a protocol based on the use of layer-by-layer adsorption of hydrophilic polyelectrolytes on the microfluidics channels, alternatively positively and negatively charged. The parts that need to be kept hydrophobic are protected by injection of dionized water at a carefully controlled flow rate.
Figure 2: Layer-by-layer coating from Bauer 
Combination of opposite wettabilities on the same microfluidic chip without any coating
More recently, other techniques were developed without any coating. They are based on a precise control of the part of the microfluidic chip exposed to plasma.
Kim et al.2 work with plasma bonded chips that have recovered their hydrophobic properties. The chip are exposed to plasma again, and oxygen ions enter into the microfluidics chips through the inlets and outlets punched in the PDMS. PDMS surface is oxidized and turns hydrophilic. Some inlet or outlet are blocked with tape during the exposure, and diffusion barriers are integrated to the chip to spatially control the ions diffusion, in the form of narrow channels. The geometry of the chip needs to be optimize to allow the oxidation of the targeted channels only.
Li et al.4 and Bodin-Thomazo et al.11 developed easy and quick techniques to pattern the wettability of the chip, by using either epoxy glue or permanent market to protect the part of the chip that need to be kept hydrophobic during the plasma treatment.
In the first case, glue is removed just before bonding, and in the later, the marker is rinsed by injecting ethanol into the chip after the bonding. In that way it is possible to combine hydrophilic and hydrophobic part on the same chip. However, since the effect of the plasma is temporary, these chips can be used to produce double emulsions only for a couple of hours before hydrophobic recovery of PDMS.
Figure 3: Wettability patterning without coatings to generate double emulsions: a) with exposure to plasma of a bonded chip (Kim et al. ), b) with epoxy glue (Li et al. )
3D-channels for the formation of double emulsions
Finally, it is possible to make monodisperse double emulsions in a microfluidic chip without any wettability patterning of the surface. To that purpose, one can generate the internal droplet at a typical cross junction with continuous phase wetting the channel walls. At the second junction, a sudden expansion of the channels allow to avoid that the droplets generated wet the walls12,13.
Figure 4: 3D-channels to generate double emulsions, from Rotem et al. 
This technique is promising but it is also demanding during the microfabrication step since the two parts of the chip need to be carefully align to recreate the whole chip.
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(1) Abate A. R.; Weitz D. A. High‐Order Multiple Emulsions Formed in Poly(Dimethylsiloxane) Microfluidics. Small 2009, 5 (18), 2030–2032. https://doi.org/10.1002/smll.200900569.
(2) Kim, S. C.; Sukovich, D. J.; Abate, A. R. Patterning Microfluidic Device Wettability with Spatially-Controlled Plasma Oxidation. Lab. Chip 2015, 15 (15), 3163–3169. https://doi.org/10.1039/C5LC00626K.
(3) Bauer, W.-A. C.; Fischlechner, M.; Abell, C.; Huck, W. T. S. Hydrophilic PDMS Microchannels for High-Throughput Formation of Oil-in-Water Microdroplets and Water-in-Oil-in-Water Double Emulsions. Lab. Chip 2010, 10 (14), 1814–1819. https://doi.org/10.1039/C004046K.
(4) Li, S.; Gong, X.; Nally, C. S. M.; Zeng, M.; Gaule, T.; Anduix-Canto, C.; Kulak, A. N.; Bawazer, L. A.; McPherson, M. J.; Meldrum, F. C. Rapid Preparation of Highly Reliable PDMS Double Emulsion Microfluidic Devices. RSC Adv. 2016, 6 (31), 25927–25933. https://doi.org/10.1039/C6RA03225G.
(5) Utada, A. S.; Lorenceau, E.; Link, D. R.; Kaplan, P. D.; Stone, H. A.; Weitz, D. A. Monodisperse Double Emulsions Generated from a Microcapillary Device. Science 2005, 308 (5721), 537–541. https://doi.org/10.1126/science.1109164.
(6) Panizza, P.; Engl, W.; Hany, C.; Backov, R. Controlled Production of Hierarchically Organized Large Emulsions and Particles Using Assemblies on Line of Co-Axial Flow Devices. Colloids Surf. Physicochem. Eng. Asp. 2008, 312 (1), 24–31. https://doi.org/10.1016/j.colsurfa.2007.06.026.
(7) Okushima, S.; Nisisako, T.; Torii, T.; Higuchi, T. Controlled Production of Monodisperse Double Emulsions by Two-Step Droplet Breakup in Microfluidic Devices. Langmuir 2004, 20 (23), 9905–9908. https://doi.org/10.1021/la0480336.
(8) Duffy, D. C.; McDonald, J. C.; Schueller, O. J. A.; Whitesides, G. M. Rapid Prototyping of Microfluidic Systems in Poly(Dimethylsiloxane). Anal. Chem. 1998, 70 (23), 4974–4984. https://doi.org/10.1021/ac980656z.
(9) Tóth, A.; Bertóti, I.; Blazsó, M.; Bánhegyi, G.; Bognar, A.; Szaplonczay, P. Oxidative Damage and Recovery of Silicone Rubber Surfaces. I. X-Ray Photoelectron Spectroscopic Study. J. Appl. Polym. Sci. 1994, 52 (9), 1293–1307. https://doi.org/10.1002/app.1994.070520914.
(10) Hu, S.; Ren, X.; Bachman, M.; Sims, C. E.; Li, G. P.; Allbritton, N. L. Surface-Directed, Graft Polymerization within Microfluidic Channels. Anal. Chem. 2004, 76 (7), 1865–1870. https://doi.org/10.1021/ac049937z.
(11) Abate, A. R.; Krummel, A. T.; Lee, D.; Marquez, M.; Holtze, C.; Weitz, D. A. Photoreactive Coating for High-Contrast Spatial Patterning of Microfluidic Device Wettability. Lab. Chip 2008, 8 (12), 2157–2160. https://doi.org/10.1039/B813405G.
(12) Chang, F.-C.; Su, Y.-C. Controlled Double Emulsification Utilizing 3D PDMS Microchannels. J. Micromechanics Microengineering 2008, 18 (6), 065018. https://doi.org/10.1088/0960-1317/18/6/065018.
(13) Rotem, A.; Abate, A. R.; Utada, A. S.; Steijn, V. V.; Weitz, D. A. Drop Formation in Non-Planar Microfluidic Devices. Lab. Chip 2012, 12 (21), 4263–4268. https://doi.org/10.1039/C2LC40546F.