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Engineering inverse opals with enclosed voids via Bottom-up assembly of double emulsions
Chemical Engineering Science 205 (2019) 414–419
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Chemical Engineering Science journal homepage: www.elsevier.com/locate/ces
Engineering inverse opals with enclosed voids via Bottom-up assembly of double emulsions Shaohua Ma Shenzhen Engineering Laboratory for Precision Medicine and Healthcare, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, PR China
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
An approach towards inverse opals
A bottom-up assembly of microfluidic double emulsions towards inverse opals with enclose voids and periodicity of tens to hundreds of microns.
with enclosed voids of 10–100 s of microns across. Bottom-up assembly of monodisperse double emulsions induces periodicity. Double emulsions with oil-removable cores generate enclosed voids. Control of double emulsions tailors the periodicity, shell thickness and void sizes. Slow crosslinking by mild heating and acidity produces ordered intact structures.
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Article history: Received 16 August 2018 Received in revised form 5 November 2018 Accepted 10 November 2018 Available online 12 November 2018 Keywords: Double emulsions Bottom-up assembly Inverse opals Sol-gel transition Microfluidics
a b s t r a c t Bottom-up assembly of monodisperse microfluidic droplets is an established route to engineer ordered structures with a periodicity of tens to hundreds of microns. When the microfluidic droplets are oil-inwater-in-oil (o/w/o) double emulsions, inverse opals with enclosed voids are derived by initiating the crosslinking within the shells and across the emulsion interfaces, accompanied by the gradual evaporation of the cores. The morphology and periodicity of the inverse opals are tailored by the emulsion size, the shell thickness, and the sol-gel transition and evaporation dynamics, etc. Ó 2018 Elsevier Ltd. All rights reserved.
1. Introduction Self-assembly has an effect on a broad range of scales, from molecular to macroscopic levels (Whitesides and Grzybowski, 2002), and bottom-up assembling nano- and micro-particles has been developed as a cost- and labor-effective approach to fabricate periodic three-dimensional (3D) structures (Lash et al., 2015; Mirkin et al., 1996; Park et al., 2008; Chen et al., 2011). Colloidal E-mail address: [email protected] https://doi.org/10.1016/j.ces.2018.11.027 0009-2509/Ó 2018 Elsevier Ltd. All rights reserved.
assemblies or the inverse replications of removable colloidal assemblies, known as opals or inverse opals, are widely explored as photonic, electronic, catalytic and structural materials (Imhof and Pine, 1997; Vlasov et al., 2001; Colvin, 2001). For instance, Holland et al. (1998) synthesized macroporous minerals with ordered spherical voids around 100 nm in size, Hatton et al. (2010) produced large-scale crack-free inverse opal films, and Vogel et al. (2015) fabricated monodisperse photonic balls in microfluidics by self-assembling nanocolloids in surface layers. Hu et al. (2001) firstly broadened the field of opals from inorganic
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materials to hydrogels by assembling polymeric nanoparticles; Pursiainen et al. (2008) developed polymer opals as structural color materials by sheer induced aligning of polymer coated nanocolloids, and Lu et al. (2014) found the regulating effect of stretched polymer inverse opal films on cell polarisation. However, opals or inverse opals templated from monodisperse microspheres in the size range of tens to hundreds of microns have been much less reported. Droplet-based microfluidics is a wellestablished platform to fabricate homogeneous simple (single) or complex emulsions (Theberge et al., 2010) and various microparticles (Xu et al., 2005; Nie et al., 2005; Ma et al., 2012; Wang et al., 2013) templated from such emulsions in high-throughput manners. Opals or inverse opals have been reported from assembled microfluidics emulsions or microparticles. For instance, Costantini et al. (2014) and Kim et al. (2015) fabricated inverse opal bio-scaffolds by crosslinking the continuous fluids carrying assembled monodisperse microparticles as removable templates; such scaffolds were proposed as new cell culture platforms with superior performance due to their high contact areas, 3D interconnectivity, and periodic structures. An alternative approach was reported using bubble-in-water-in-oil double emulsions as constituent units and the crosslinked aqueous middle phase constituting the scaffold (Wang et al., 2011). Recently, Zhu et al. engineered precisely controlled microstructures with periodic through-pores or dead-end pores, by applying evaporation-induced selfassembly of microdroplets (Zhu et al., 2018). Here we introduce a new inverse silica opal structure with enclosed voids about 50–100 mm in size, fabricated by intercon-
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necting the middle aqueous shells of bottom-up assembled monodisperse oil-in-water-in-oil (o/w/o) double emulsions via hydrolysis induced sol-gel transition of the middle phases (Zhao et al., 1998). Double emulsions were formed in microfluidics by single step co-emulsification of inner oil and middle aqueous phases (Adams et al., 2012) and acidic silicate was used as the middle phase. Sizes of enclosed voids, structural periodicity and packing morphology were determined by the core and shell sizes of the templating double emulsions. Inverse opals formed by the crosslinking reaction occurred at the interfaces, accompanied by the evaporation of the cores. 2. Results and discussion Monodisperse o/w/o double emulsions were formed in microfluidics, as sketched in Fig. 1a, by single step emulsification (Adams et al., 2012). The inner oil phase (red), the middle aqueous phase (blue) and the outer oil phases (grey) were injected independently into microfluidics channels via the three inlets. The inner oil stream was focused by the middle aqueous phase in the hydrophilic region A; at the second flow-focusing junction, the oil-aqueous parallel stream was co-emulsified by the continuous oil flow, forming double emulsions in single step in region B. Double emulsions were conducted from the device outlet into an Eppendorf tube via a polyethylene (PE) tubing. As the carrier oil HFE7500 has larger density, double emulsions assembled in the upper layer; the excess carrier oil in the tube bottom was aspirated out by pipetting and the remaining were incubated at 60 °C for 24 h, with the cap closed
Fig. 1. Diagram of bottom-up fabrication of inverse silica opals with enclosed voids. (a) O/w/o double emulsion produced in surface-treated microfluidics. Region A (60 lm wide) and B (120 lm wide) were modified hydrophilic and hydrophobic selectively by flowing polyelectrolyte or silane solutions, respectively. The entire channel was 75 mm deep. (b) Steps of fabricating inverse opals by the sol-gel transition of assembled double emulsions: b1, double emulsions assembled in a tube; b2: the excess carrier oil was removed; b3: the sol-gel transition of shells induced inverse opals formation. (c) Photos of (c1) double emulsions assembled in a tube, and (c2) an inverse opal network extracted out of the tube. (d) Bright field images of sol-gel transition of single-layered double emulsions on a glass slide. Scale bar: 80 mm. (e) Diagram of single-layered inverse opal with enclosed voids. (f) Chemical structures of silicate and silica.
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to allow sol-gel transition, followed by another 48 h with the cap open at 60 °C to evaporate the core oil. (Fig. 1b) In this process, the shells were hydrolyzed from flowable silicate into solid silica, associated with shape transformation of the constituent units. The photos of double emulsions assembled in a tube, and an inverse opal structure after sol-gel transition and the core oil evaporation are shown in Fig. 1c. To elucidate the organisation of inverse opals, double emulsions assembled on a glass slide as a layered two-dimensional (2D) model; individual emulsions underwent irreversible shape transformation from microspheres dominated by the surface tension energy to hexahedrons induced by close packing after sol-gel transition, with cores enclosed by interconnected silica shells; after evaporating the core oil, the shell films wrinkled, but the hexagonal array sustained. (Fig. 1d) The single-layered array is sketched in Fig. 1e: the hexagonally arranged silica templated from the emulsion shells constitutes the inverse opal scaffold, which encloses periodically distributed voids templated from the oil cores. The cores exhibited round projections in the layered array but the core morphologies were steered by the shell-to-core volume ratios, which will be shown in Fig. 4. The chemical structures of silicate (TEOS) and silica (SiO2) are given in Fig. 1f. When both the inner and outer phases were HFE7500 oil, double emulsions became unstable when the middle phase went through a sol-gel transition, which was accompanied by the core merging with the continuous oil, bursting a hole in the shell, and yielding solid microspheres with an open void. (Fig. 2a and b) By decreasing the flow rate of the outer oil phase, larger emulsions comprising two oil cores in each shell were obtained, yielding
microspheres with dual open voids after the sol-gel transition. (Fig. 2c and d). Double emulsion stability in sol-gel transition was enhanced by adopting dodecane as the inner oil phase, which has low solubility in HFE7500 (the outer oil phase), to fabricate inverse opals. To validate that the oil cores transformed into voids rather than solids, double emulsions were assembled and incubated at an elevated temperature (90 °C) for a more extended period (5 days); the obtained structures had either concave shells or ruptured shells exhibiting voids in Fig. 2e. Double emulsion morphology was regulated by tuning the injection flow rate ratio of the middle aqueous phase, Qm, to the inner oil phase, Qi, while maintaining the flow rates of the outer oil phase and the sum of Qm and Qi. Qm : Qi ranged from 3:1 to 1:1. Double emulsions were approximately constant in size but decreased in shell-to-core size ratio Vm:Vi, sequentially (Fig. 3a), which correlated linearly with the flow rate ratio Qm:Qi (Fig. 3b). Emulsion sizes were measured from 2D projected images of double emulsions redeposited on glass slides and volumes were calculated from their diameters. The slope of Vm:Vi against Qm:Qi was slightly larger than 1, and the deviation was possibly attributed to two factors: (1) the error in volume estimation from the cross-sectional area of shells and cores, which were slightly deformed by gravity; (2) the inner oil phase (dodecane with Span 80) had higher solubility than the middle aqueous phase (mixture of TEOS and Gly) in the outer oil (HFE7500 with PS-1), resulting in increased Vm:Vi. We investigated the fabrication of inverse opals by assembling and gelling double emulsions as formed in Fig. 3. In most cases, emulsion spheres were collected and tightly packed in an Eppen-
Fig. 2. Microspheres with open/closed voids after the sol-gel transition of emulsion shells. (a–d) Bright-field images of o/w/o double emulsions with (a, b) single oil cores and (c, d) dual cores, (a, c) before and (b, d) after sol-gel transition at 60 °C for 24 h. Both the inner and outer oil phases were HFE7500 with 1.5 wt% PS-1 surfactant. (e) SEM images of over incubated double emulsion assembled in a closed Eppendorf tube for 24 h followed by 96 h in the open tube at 90 °C. Scale bar: 80 mm.
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dorf tube, in either hexagonal or face-centred cubic packing; the emulsions were incubated sequentially in a closed (24 h, 60 °C) and an open (48 h, 60 °C) tube at varied Qm : Qi ranging from 3:1 to 1:1, corresponding to decreased shell-to-core volume ratios Vm:Vi. In Fig. 4a–c, the emulsion spheres, with Qm:Qi = 3:1, 2:1 and 3:2, expanded uniformly in the sol-gel transition into polyhedrons, either trapezo-rhombic dodecahedrons or rhombic dodecahedrons (Ko, 1965). Though both types of transformation resulted in equal volumes, it was not evident enough to ascertain the packing form or the expanded morphology only from the projected images of unit cells being uniformly hexagonal. The volume of trapezo-rhombic or rhombic dodecahedrons was
V ¼ 0:707p3 ;
Fig. 3. Controlled formation of o/w/o double emulsions. (a) Tuning double emulsion morphology by varying the flow rate ratio Qm:Qi from 3:1 to 1:1. (b) Linear correlation of the volume ratio Vm:Vi against the flow rate ratio Qm:Qi. Scale bar: 80 mm.
where p is the periodicity of each unit cell (Alsina and Nelsen, 2015). The periodicity of the array along the colored lines in Fig. 4a–d is shown in Fig. 4e; from Qm:Qi = 3:1 to 1:1, the periodicity only decreased insignificantly when the templating double emulsions were approximately identical in size. However, at Qm: Qi = 1:1, as the shell volume was substantially reduced, the emulsion spheres expanded into cubes and packed differently. It must be noted that this transition was not as reliable, seen from the non-homogeneous morphologies of unit cells in Fig. 4d. Presumably, decreased shell volume fraction (and increased core volume fraction) would result in smaller silica intervals associated with varying void shapes and sizes in the obtained inverse opals, which was validated by the images in Fig. 4a–d and the plotted graph in Fig. 4f. From Fig. 4a to b, the core volume increased by 33% (from 25% to 33%), and the voids transformed from spheres to trapezo-rhombic or rhombic dodecahedrons, and accordingly, the intervals decreased significantly from 11.8 mm to 10.2 mm
Fig. 4. Inverse opals assembled from double emulsions of varying shell-to-core size ratios. (a–d) SEM images of inverse opals at different magnifications of varying Qm:Qi: (a) Qm:Qi = 3:1; (b) Qm:Qi = 2:1; (c) Qm:Qi = 3:2; (d) Qm:Qi = 1:1. Double emulsions were gelled in a closed Eppendorf tube for 24 h at 60 °C followed by another 48 h in the open tube at 60 °C. Scale bar: 80 mm. (e) Periodicity of the inverse opals along the colored lines in (a–d). (f) Interval d, as indicated by the yellow dashes, between the enclosed voids, and the calculated shell-to-void volume ratio Vs:Vv of each unit cell against Qm:Qi. Scale bar: 80 mm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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(Fig. 4f). From Fig. 4b to c, the core volume increased by 21% (from 33% to 40%), and the voids maintained trapezo-rhombic or rhombic dodecahedrons but the intervals decreased significantly from 10.2 mm to 7.5 mm (Fig. 4f). From Fig. 4c to d, the core volume increased by 25% (from 40% to 50%), and the void shapes transformed from trapezo-rhombic or rhombic dodecahedrons to cubes, and the intervals decreased significantly from 7.5 mm to 6.2 mm (Fig. 4f). The shell-to-void volume ratio (Vm:Vv) in the inverse opals were calculated and plotted in Fig. 4f. The Vm:Vv followed similar trend against Qm:Qi as the interval d: at Qm:Qi = 3:1, 2:1, 3:2 and 1:1, Vm:Vv decreased from 1.0 to 0.8, 0.5 and 0.3, accordingly.
3. Conclusions Inter-particle (or micelle, vesicle, etc) sol-gel transition of silicate to silica has been a major step in the fabrication of ordered mesoporous materials, with pore size / periodicity in the range of a few to tens of nanometers (Zhao et al., 2000). This work was the first to apply the inter-particle (or inter-droplet) solgel transition in the dimensions of tens to hundreds of microns. Assembled o/w/o double emulsions were used as templates to fabricate 3D inverse silica opals with enclosed voids of tens to hundreds of microns in size, by the thermo-facilitated sol-gel transition of the middle aqueous phase (acidic silicate) and evaporation of the core oil. The oil cores maintained spherical by the surface tension energy prior to the sol-gel transition and formed close packing; gelling the middle phase formed trapezo-rhombic or rhombic dodecahedron unit cells framing re-morphed oil cores (spheres or trapezo-rhombic/rhombic dodecahedrons); inverse opals were obtained after evaporating core oil under prolonged incubation. Voids and intervals were tailorable in size by varying the flow rate ratio of the shell-to-core phases: by decreasing the flow rate ratio, the interval decreased, and the enclosed voids transform from spheres to trapezo-rhombic/ rhombic dodecahedrons. By decreasing the shell-to-core volume ratio to unity, both shells and cores of emulsions spheres were found transformed into cubes, and the intervals were decreased to minimal; however, such shape transformation was not as uniform and controllable as the former cases. The sol-gel transition is a slow process, and the ordered structure formation require minimum disturbance during gelation. pH and temperature are the most important factors that determine the sol-gel transition speed. Overheat (e.g. incubation at 90 °C) or very low pH (e.g. pH < 2) conditions induced shell rupture. (Fig. 2) Mild heating (e.g. incubation at 60 °C) and mild acidity (e.g. pH 3) were preferred to obtain ordered intact enclosed voids. Another key factor was to first introduce the gelation at an enclosed environment to prevent water and oil evaporation, followed with an open environment that allowed gradual evaporation when the inter-droplet gelation has occurred. The uniform long range morphologies of inverse opals and tailorable interval sizes suggest that the inverse opals may have a range of applications, including the light-weight structural materials for high-end uses owing to their macroporosity. As suggested by the literature, silica is a physiologically compatible materials (Xuan et al., 2015; van Rijt et al., 2015), which might enable the inverse opals as the insulin controlled release device to be implanted beneath the skin. The enclosed voids function as large volume reserviors for insulin, by loading insulin into the macropores under high pressure; their interconnectivity allows rapid in vivo transport of insulin from the bulk interior to the periphery. When the shell phases of the templating double emulsions are suspended with nanoparticles (Shang et al., 2017; Zhao et al., 2012), the inverse opals could be developed into a biophotonic material. Ordered macroporous structures have also been suggested as
energy storage and conversion systems, because they provide large surface areas for reaction, interfacial transport, or dispersion of active sites for catalysis or energy conversion (Li et al., 2012). 4. Experimental section All chemicals were used as purchased from commercial suppliers without further purification. Deionised water (DIW) was used in all aqueous phases. Polydimethylsiloxane (PDMS) microfluidic devices were fabricated by the combined photo- and softlithography (Xia and Whitesides, 1998; Ma et al., 2014). The microchannel master was fabricated by spin-coating 75 lm SU82025 (MicroChem, USA) onto a 3-inch silicon wafer (Compart Technology Ltd. UK), followed by pre-bake, UV exposure, and post-bake, according to the protocol from the SU8 supplier. The microchannel geometry is illustrated in Fig. 1a. Channel surface was modified selectively for o/w/o double emulsion formation, by sequentially depositing positively and negatively charged polyelectrolytes layer-by-layer or flushing silane in selected regions (Bauer et al., 2010), obtaining the region between the first and second flow focusing junctions (region A, 60 lm wide) being hydrophilic and the region downstream of the second flow-focusing junction (region B, 120 lm wide) hydrophobic. All fluids were delivered to the microchannels by syringe pumps (PHD 2000 Infusion Pump, Harvard Apparatus, USA) at flow rates varying from 100 to 2000 ml/hr. O/w/o double emulsions were generated by sequentially injecting the inner oil, middle aqueous and outer oil phases from the three inlets. (Fig. 1a) Pico-surf 1 surfactant (PS-1, Sphere Fluidics Ltd, UK) were loaded at 1.5 wt% in the fluorinated oil HFE7500 (3 M, USA) throughout the experiments as the outer oil phase. The middle aqueous phase was the equal volume mixture of tetraethyl orthosilicate (TEOS) and glycerol (Gly), which was added to tune the phase viscosity and surface tension to assist co-emulsification (Wan and Stone, 2012); pH was adjusted to 4.0 using hydrochloric acid (HCl) to accelerate the sol-gel transition. Hydrocarbon oil dodecane, loaded with 2.0 wt% Span 80 surfactant, was used as the inner oil phase, except for the emulsions shown in Fig. 2a–d. Bright field images were acquired using a high-speed CMOS camera (Phantom v7.2, Vision Research, USA) attached on an inverted microscope (Olympus IX71, Olympus Optical Co. Ltd, Japan). For SEM analysis, bulk networks were freeze-dried (VirTis Bench Top L Manifold freeze drier) at –75 °C, coated with gold and imaged in a Leo Ultra55 field emission SEM (Zeiss, Germany) at an acceleration voltage of 5 kV. The acquired images were processed using the open source software ImageJTM. Acknowledgements The work is funded by Shenzhen Municipal Development and Reform Commission, Shenzhen Engineering Laboratory for Precision Medicine and Healthcare, Grant Number: SDRC [2015]1950. The work is also funded by the scientific research start-up fund of Tsinghua-Berkeley Shenzhen Institute. Conflict of interest The authors declare no conflict of interest. References Adams, L.L.A., Kodger, T.E., Kim, S.H., Shum, H.C., Franke, T., Weitz, D.A., 2012. Single step emulsification for the generation of multi-component double emulsions. Soft Matter 8 (41), 10719–10724. Alsina, C., Nelsen, R.B., 2015. A Mathematical Space Odyssey: Solid Geometry in the 21st Century. American Mathematical Society. UK ed.
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Chemical Engineering Science journal homepage: www.elsevier.com/locate/ces
Engineering inverse opals with enclosed voids via Bottom-up assembly of double emulsions Shaohua Ma Shenzhen Engineering Laboratory for Precision Medicine and Healthcare, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, PR China
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
An approach towards inverse opals
A bottom-up assembly of microfluidic double emulsions towards inverse opals with enclose voids and periodicity of tens to hundreds of microns.
with enclosed voids of 10–100 s of microns across. Bottom-up assembly of monodisperse double emulsions induces periodicity. Double emulsions with oil-removable cores generate enclosed voids. Control of double emulsions tailors the periodicity, shell thickness and void sizes. Slow crosslinking by mild heating and acidity produces ordered intact structures.
a r t i c l e
i n f o
Article history: Received 16 August 2018 Received in revised form 5 November 2018 Accepted 10 November 2018 Available online 12 November 2018 Keywords: Double emulsions Bottom-up assembly Inverse opals Sol-gel transition Microfluidics
a b s t r a c t Bottom-up assembly of monodisperse microfluidic droplets is an established route to engineer ordered structures with a periodicity of tens to hundreds of microns. When the microfluidic droplets are oil-inwater-in-oil (o/w/o) double emulsions, inverse opals with enclosed voids are derived by initiating the crosslinking within the shells and across the emulsion interfaces, accompanied by the gradual evaporation of the cores. The morphology and periodicity of the inverse opals are tailored by the emulsion size, the shell thickness, and the sol-gel transition and evaporation dynamics, etc. Ó 2018 Elsevier Ltd. All rights reserved.
1. Introduction Self-assembly has an effect on a broad range of scales, from molecular to macroscopic levels (Whitesides and Grzybowski, 2002), and bottom-up assembling nano- and micro-particles has been developed as a cost- and labor-effective approach to fabricate periodic three-dimensional (3D) structures (Lash et al., 2015; Mirkin et al., 1996; Park et al., 2008; Chen et al., 2011). Colloidal E-mail address: [email protected] https://doi.org/10.1016/j.ces.2018.11.027 0009-2509/Ó 2018 Elsevier Ltd. All rights reserved.
assemblies or the inverse replications of removable colloidal assemblies, known as opals or inverse opals, are widely explored as photonic, electronic, catalytic and structural materials (Imhof and Pine, 1997; Vlasov et al., 2001; Colvin, 2001). For instance, Holland et al. (1998) synthesized macroporous minerals with ordered spherical voids around 100 nm in size, Hatton et al. (2010) produced large-scale crack-free inverse opal films, and Vogel et al. (2015) fabricated monodisperse photonic balls in microfluidics by self-assembling nanocolloids in surface layers. Hu et al. (2001) firstly broadened the field of opals from inorganic
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materials to hydrogels by assembling polymeric nanoparticles; Pursiainen et al. (2008) developed polymer opals as structural color materials by sheer induced aligning of polymer coated nanocolloids, and Lu et al. (2014) found the regulating effect of stretched polymer inverse opal films on cell polarisation. However, opals or inverse opals templated from monodisperse microspheres in the size range of tens to hundreds of microns have been much less reported. Droplet-based microfluidics is a wellestablished platform to fabricate homogeneous simple (single) or complex emulsions (Theberge et al., 2010) and various microparticles (Xu et al., 2005; Nie et al., 2005; Ma et al., 2012; Wang et al., 2013) templated from such emulsions in high-throughput manners. Opals or inverse opals have been reported from assembled microfluidics emulsions or microparticles. For instance, Costantini et al. (2014) and Kim et al. (2015) fabricated inverse opal bio-scaffolds by crosslinking the continuous fluids carrying assembled monodisperse microparticles as removable templates; such scaffolds were proposed as new cell culture platforms with superior performance due to their high contact areas, 3D interconnectivity, and periodic structures. An alternative approach was reported using bubble-in-water-in-oil double emulsions as constituent units and the crosslinked aqueous middle phase constituting the scaffold (Wang et al., 2011). Recently, Zhu et al. engineered precisely controlled microstructures with periodic through-pores or dead-end pores, by applying evaporation-induced selfassembly of microdroplets (Zhu et al., 2018). Here we introduce a new inverse silica opal structure with enclosed voids about 50–100 mm in size, fabricated by intercon-
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necting the middle aqueous shells of bottom-up assembled monodisperse oil-in-water-in-oil (o/w/o) double emulsions via hydrolysis induced sol-gel transition of the middle phases (Zhao et al., 1998). Double emulsions were formed in microfluidics by single step co-emulsification of inner oil and middle aqueous phases (Adams et al., 2012) and acidic silicate was used as the middle phase. Sizes of enclosed voids, structural periodicity and packing morphology were determined by the core and shell sizes of the templating double emulsions. Inverse opals formed by the crosslinking reaction occurred at the interfaces, accompanied by the evaporation of the cores. 2. Results and discussion Monodisperse o/w/o double emulsions were formed in microfluidics, as sketched in Fig. 1a, by single step emulsification (Adams et al., 2012). The inner oil phase (red), the middle aqueous phase (blue) and the outer oil phases (grey) were injected independently into microfluidics channels via the three inlets. The inner oil stream was focused by the middle aqueous phase in the hydrophilic region A; at the second flow-focusing junction, the oil-aqueous parallel stream was co-emulsified by the continuous oil flow, forming double emulsions in single step in region B. Double emulsions were conducted from the device outlet into an Eppendorf tube via a polyethylene (PE) tubing. As the carrier oil HFE7500 has larger density, double emulsions assembled in the upper layer; the excess carrier oil in the tube bottom was aspirated out by pipetting and the remaining were incubated at 60 °C for 24 h, with the cap closed
Fig. 1. Diagram of bottom-up fabrication of inverse silica opals with enclosed voids. (a) O/w/o double emulsion produced in surface-treated microfluidics. Region A (60 lm wide) and B (120 lm wide) were modified hydrophilic and hydrophobic selectively by flowing polyelectrolyte or silane solutions, respectively. The entire channel was 75 mm deep. (b) Steps of fabricating inverse opals by the sol-gel transition of assembled double emulsions: b1, double emulsions assembled in a tube; b2: the excess carrier oil was removed; b3: the sol-gel transition of shells induced inverse opals formation. (c) Photos of (c1) double emulsions assembled in a tube, and (c2) an inverse opal network extracted out of the tube. (d) Bright field images of sol-gel transition of single-layered double emulsions on a glass slide. Scale bar: 80 mm. (e) Diagram of single-layered inverse opal with enclosed voids. (f) Chemical structures of silicate and silica.
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to allow sol-gel transition, followed by another 48 h with the cap open at 60 °C to evaporate the core oil. (Fig. 1b) In this process, the shells were hydrolyzed from flowable silicate into solid silica, associated with shape transformation of the constituent units. The photos of double emulsions assembled in a tube, and an inverse opal structure after sol-gel transition and the core oil evaporation are shown in Fig. 1c. To elucidate the organisation of inverse opals, double emulsions assembled on a glass slide as a layered two-dimensional (2D) model; individual emulsions underwent irreversible shape transformation from microspheres dominated by the surface tension energy to hexahedrons induced by close packing after sol-gel transition, with cores enclosed by interconnected silica shells; after evaporating the core oil, the shell films wrinkled, but the hexagonal array sustained. (Fig. 1d) The single-layered array is sketched in Fig. 1e: the hexagonally arranged silica templated from the emulsion shells constitutes the inverse opal scaffold, which encloses periodically distributed voids templated from the oil cores. The cores exhibited round projections in the layered array but the core morphologies were steered by the shell-to-core volume ratios, which will be shown in Fig. 4. The chemical structures of silicate (TEOS) and silica (SiO2) are given in Fig. 1f. When both the inner and outer phases were HFE7500 oil, double emulsions became unstable when the middle phase went through a sol-gel transition, which was accompanied by the core merging with the continuous oil, bursting a hole in the shell, and yielding solid microspheres with an open void. (Fig. 2a and b) By decreasing the flow rate of the outer oil phase, larger emulsions comprising two oil cores in each shell were obtained, yielding
microspheres with dual open voids after the sol-gel transition. (Fig. 2c and d). Double emulsion stability in sol-gel transition was enhanced by adopting dodecane as the inner oil phase, which has low solubility in HFE7500 (the outer oil phase), to fabricate inverse opals. To validate that the oil cores transformed into voids rather than solids, double emulsions were assembled and incubated at an elevated temperature (90 °C) for a more extended period (5 days); the obtained structures had either concave shells or ruptured shells exhibiting voids in Fig. 2e. Double emulsion morphology was regulated by tuning the injection flow rate ratio of the middle aqueous phase, Qm, to the inner oil phase, Qi, while maintaining the flow rates of the outer oil phase and the sum of Qm and Qi. Qm : Qi ranged from 3:1 to 1:1. Double emulsions were approximately constant in size but decreased in shell-to-core size ratio Vm:Vi, sequentially (Fig. 3a), which correlated linearly with the flow rate ratio Qm:Qi (Fig. 3b). Emulsion sizes were measured from 2D projected images of double emulsions redeposited on glass slides and volumes were calculated from their diameters. The slope of Vm:Vi against Qm:Qi was slightly larger than 1, and the deviation was possibly attributed to two factors: (1) the error in volume estimation from the cross-sectional area of shells and cores, which were slightly deformed by gravity; (2) the inner oil phase (dodecane with Span 80) had higher solubility than the middle aqueous phase (mixture of TEOS and Gly) in the outer oil (HFE7500 with PS-1), resulting in increased Vm:Vi. We investigated the fabrication of inverse opals by assembling and gelling double emulsions as formed in Fig. 3. In most cases, emulsion spheres were collected and tightly packed in an Eppen-
Fig. 2. Microspheres with open/closed voids after the sol-gel transition of emulsion shells. (a–d) Bright-field images of o/w/o double emulsions with (a, b) single oil cores and (c, d) dual cores, (a, c) before and (b, d) after sol-gel transition at 60 °C for 24 h. Both the inner and outer oil phases were HFE7500 with 1.5 wt% PS-1 surfactant. (e) SEM images of over incubated double emulsion assembled in a closed Eppendorf tube for 24 h followed by 96 h in the open tube at 90 °C. Scale bar: 80 mm.
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dorf tube, in either hexagonal or face-centred cubic packing; the emulsions were incubated sequentially in a closed (24 h, 60 °C) and an open (48 h, 60 °C) tube at varied Qm : Qi ranging from 3:1 to 1:1, corresponding to decreased shell-to-core volume ratios Vm:Vi. In Fig. 4a–c, the emulsion spheres, with Qm:Qi = 3:1, 2:1 and 3:2, expanded uniformly in the sol-gel transition into polyhedrons, either trapezo-rhombic dodecahedrons or rhombic dodecahedrons (Ko, 1965). Though both types of transformation resulted in equal volumes, it was not evident enough to ascertain the packing form or the expanded morphology only from the projected images of unit cells being uniformly hexagonal. The volume of trapezo-rhombic or rhombic dodecahedrons was
V ¼ 0:707p3 ;
Fig. 3. Controlled formation of o/w/o double emulsions. (a) Tuning double emulsion morphology by varying the flow rate ratio Qm:Qi from 3:1 to 1:1. (b) Linear correlation of the volume ratio Vm:Vi against the flow rate ratio Qm:Qi. Scale bar: 80 mm.
where p is the periodicity of each unit cell (Alsina and Nelsen, 2015). The periodicity of the array along the colored lines in Fig. 4a–d is shown in Fig. 4e; from Qm:Qi = 3:1 to 1:1, the periodicity only decreased insignificantly when the templating double emulsions were approximately identical in size. However, at Qm: Qi = 1:1, as the shell volume was substantially reduced, the emulsion spheres expanded into cubes and packed differently. It must be noted that this transition was not as reliable, seen from the non-homogeneous morphologies of unit cells in Fig. 4d. Presumably, decreased shell volume fraction (and increased core volume fraction) would result in smaller silica intervals associated with varying void shapes and sizes in the obtained inverse opals, which was validated by the images in Fig. 4a–d and the plotted graph in Fig. 4f. From Fig. 4a to b, the core volume increased by 33% (from 25% to 33%), and the voids transformed from spheres to trapezo-rhombic or rhombic dodecahedrons, and accordingly, the intervals decreased significantly from 11.8 mm to 10.2 mm
Fig. 4. Inverse opals assembled from double emulsions of varying shell-to-core size ratios. (a–d) SEM images of inverse opals at different magnifications of varying Qm:Qi: (a) Qm:Qi = 3:1; (b) Qm:Qi = 2:1; (c) Qm:Qi = 3:2; (d) Qm:Qi = 1:1. Double emulsions were gelled in a closed Eppendorf tube for 24 h at 60 °C followed by another 48 h in the open tube at 60 °C. Scale bar: 80 mm. (e) Periodicity of the inverse opals along the colored lines in (a–d). (f) Interval d, as indicated by the yellow dashes, between the enclosed voids, and the calculated shell-to-void volume ratio Vs:Vv of each unit cell against Qm:Qi. Scale bar: 80 mm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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(Fig. 4f). From Fig. 4b to c, the core volume increased by 21% (from 33% to 40%), and the voids maintained trapezo-rhombic or rhombic dodecahedrons but the intervals decreased significantly from 10.2 mm to 7.5 mm (Fig. 4f). From Fig. 4c to d, the core volume increased by 25% (from 40% to 50%), and the void shapes transformed from trapezo-rhombic or rhombic dodecahedrons to cubes, and the intervals decreased significantly from 7.5 mm to 6.2 mm (Fig. 4f). The shell-to-void volume ratio (Vm:Vv) in the inverse opals were calculated and plotted in Fig. 4f. The Vm:Vv followed similar trend against Qm:Qi as the interval d: at Qm:Qi = 3:1, 2:1, 3:2 and 1:1, Vm:Vv decreased from 1.0 to 0.8, 0.5 and 0.3, accordingly.
3. Conclusions Inter-particle (or micelle, vesicle, etc) sol-gel transition of silicate to silica has been a major step in the fabrication of ordered mesoporous materials, with pore size / periodicity in the range of a few to tens of nanometers (Zhao et al., 2000). This work was the first to apply the inter-particle (or inter-droplet) solgel transition in the dimensions of tens to hundreds of microns. Assembled o/w/o double emulsions were used as templates to fabricate 3D inverse silica opals with enclosed voids of tens to hundreds of microns in size, by the thermo-facilitated sol-gel transition of the middle aqueous phase (acidic silicate) and evaporation of the core oil. The oil cores maintained spherical by the surface tension energy prior to the sol-gel transition and formed close packing; gelling the middle phase formed trapezo-rhombic or rhombic dodecahedron unit cells framing re-morphed oil cores (spheres or trapezo-rhombic/rhombic dodecahedrons); inverse opals were obtained after evaporating core oil under prolonged incubation. Voids and intervals were tailorable in size by varying the flow rate ratio of the shell-to-core phases: by decreasing the flow rate ratio, the interval decreased, and the enclosed voids transform from spheres to trapezo-rhombic/ rhombic dodecahedrons. By decreasing the shell-to-core volume ratio to unity, both shells and cores of emulsions spheres were found transformed into cubes, and the intervals were decreased to minimal; however, such shape transformation was not as uniform and controllable as the former cases. The sol-gel transition is a slow process, and the ordered structure formation require minimum disturbance during gelation. pH and temperature are the most important factors that determine the sol-gel transition speed. Overheat (e.g. incubation at 90 °C) or very low pH (e.g. pH < 2) conditions induced shell rupture. (Fig. 2) Mild heating (e.g. incubation at 60 °C) and mild acidity (e.g. pH 3) were preferred to obtain ordered intact enclosed voids. Another key factor was to first introduce the gelation at an enclosed environment to prevent water and oil evaporation, followed with an open environment that allowed gradual evaporation when the inter-droplet gelation has occurred. The uniform long range morphologies of inverse opals and tailorable interval sizes suggest that the inverse opals may have a range of applications, including the light-weight structural materials for high-end uses owing to their macroporosity. As suggested by the literature, silica is a physiologically compatible materials (Xuan et al., 2015; van Rijt et al., 2015), which might enable the inverse opals as the insulin controlled release device to be implanted beneath the skin. The enclosed voids function as large volume reserviors for insulin, by loading insulin into the macropores under high pressure; their interconnectivity allows rapid in vivo transport of insulin from the bulk interior to the periphery. When the shell phases of the templating double emulsions are suspended with nanoparticles (Shang et al., 2017; Zhao et al., 2012), the inverse opals could be developed into a biophotonic material. Ordered macroporous structures have also been suggested as
energy storage and conversion systems, because they provide large surface areas for reaction, interfacial transport, or dispersion of active sites for catalysis or energy conversion (Li et al., 2012). 4. Experimental section All chemicals were used as purchased from commercial suppliers without further purification. Deionised water (DIW) was used in all aqueous phases. Polydimethylsiloxane (PDMS) microfluidic devices were fabricated by the combined photo- and softlithography (Xia and Whitesides, 1998; Ma et al., 2014). The microchannel master was fabricated by spin-coating 75 lm SU82025 (MicroChem, USA) onto a 3-inch silicon wafer (Compart Technology Ltd. UK), followed by pre-bake, UV exposure, and post-bake, according to the protocol from the SU8 supplier. The microchannel geometry is illustrated in Fig. 1a. Channel surface was modified selectively for o/w/o double emulsion formation, by sequentially depositing positively and negatively charged polyelectrolytes layer-by-layer or flushing silane in selected regions (Bauer et al., 2010), obtaining the region between the first and second flow focusing junctions (region A, 60 lm wide) being hydrophilic and the region downstream of the second flow-focusing junction (region B, 120 lm wide) hydrophobic. All fluids were delivered to the microchannels by syringe pumps (PHD 2000 Infusion Pump, Harvard Apparatus, USA) at flow rates varying from 100 to 2000 ml/hr. O/w/o double emulsions were generated by sequentially injecting the inner oil, middle aqueous and outer oil phases from the three inlets. (Fig. 1a) Pico-surf 1 surfactant (PS-1, Sphere Fluidics Ltd, UK) were loaded at 1.5 wt% in the fluorinated oil HFE7500 (3 M, USA) throughout the experiments as the outer oil phase. The middle aqueous phase was the equal volume mixture of tetraethyl orthosilicate (TEOS) and glycerol (Gly), which was added to tune the phase viscosity and surface tension to assist co-emulsification (Wan and Stone, 2012); pH was adjusted to 4.0 using hydrochloric acid (HCl) to accelerate the sol-gel transition. Hydrocarbon oil dodecane, loaded with 2.0 wt% Span 80 surfactant, was used as the inner oil phase, except for the emulsions shown in Fig. 2a–d. Bright field images were acquired using a high-speed CMOS camera (Phantom v7.2, Vision Research, USA) attached on an inverted microscope (Olympus IX71, Olympus Optical Co. Ltd, Japan). For SEM analysis, bulk networks were freeze-dried (VirTis Bench Top L Manifold freeze drier) at –75 °C, coated with gold and imaged in a Leo Ultra55 field emission SEM (Zeiss, Germany) at an acceleration voltage of 5 kV. The acquired images were processed using the open source software ImageJTM. Acknowledgements The work is funded by Shenzhen Municipal Development and Reform Commission, Shenzhen Engineering Laboratory for Precision Medicine and Healthcare, Grant Number: SDRC [2015]1950. The work is also funded by the scientific research start-up fund of Tsinghua-Berkeley Shenzhen Institute. Conflict of interest The authors declare no conflict of interest. References Adams, L.L.A., Kodger, T.E., Kim, S.H., Shum, H.C., Franke, T., Weitz, D.A., 2012. Single step emulsification for the generation of multi-component double emulsions. Soft Matter 8 (41), 10719–10724. Alsina, C., Nelsen, R.B., 2015. A Mathematical Space Odyssey: Solid Geometry in the 21st Century. American Mathematical Society. UK ed.
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