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Controlled Generation of Monodisperse Discoid Droplets Using Microchannel Arrays Isao Kobayashi, Kunihiko Uemura, and Mitsutoshi Nakajima* Food Engineering DiVision, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan ReceiVed August 7, 2006 We report a novel technique for generating geometrically confined droplets using a unique microstructure composed of a microchannel (MC) array and a shallow well. Silicon MC array devices were successfully used to generate monodisperse discoid droplets of oil-in-water (O/W) and W/O types by forcing a to-be-dispersed phase through channels into a well filled with a continuous phase. Monodisperse discoid droplets with sizes down to several micrometers were obtained by controlling the channel and well dimensions. The resultant discoid droplets formed a mostly closepacked array in the well. Monodisperse discoid droplets consisting of a silicone oil/water/sodium dodecyl sulfate system did not coalesce during the storage time of seven days. Additionally, MC array plates with many channels can be useful for increasing the droplet productivity of a single microfluidic device.
An emulsion is a liquid-liquid dispersion in which droplets of one liquid (a to-be-dispersed phase) are dispersed in a second immiscible liquid (a continuous phase). Emulsion droplets dispersed in a macrospace inherently form a sphere, since spherical droplets have the smallest possible interfacial area and thus minimize the interfacial free energy. Monodisperse emulsions with a coefficient of variation (CV; standard deviation/average droplet diameter × 100) of less than 5% are useful for controlling, predicting, and measuring many important emulsion properties.1,2 In particular, monodisperse emulsions have greater stability against droplet coalescence than polydisperse emulsions. Membrane emulsification enables the direct generation of quasimonodisperse emulsion droplets with a CV of about 10% by forcing a to-be-dispersed phase through a microporous membrane into a continuous phase.3-6 Several techniques also have been proposed to reduce the droplet size distribution of premixed polydisperse emulsions.7-9 Typically, the emulsion droplets generated using the above techniques are spherical. Recently, microfluidic devices with interconnected channel networks have been proposed to generate monodisperse emulsion droplets with an average size greater than 10 µm by applying a rapidly flowing continuous phase.10-15 These microfluidic * Author to whom correspondence should be addressed. Telephone: +8129-838-8014, Fax: +81-29-838-7996, E-mail:
[email protected]. (1) McClements, D. J. Food Emulsions: Principles, Practice and Techniques, 2nd ed.; CRC Press: Boca Raton, FL, 2004; Chapter 1. (2) Mason, T. G.; Krall, A. H.; Gang, H.; Bibette, J; Weitz, D. A. In Encyclopedia of Emulsion Technology; Becher, P., Ed.; Marcel Dekker: New York, 1996; Vol. 2, Chapter 6. (3) Nakashima, T.; Shimizu, M.; Kukizaki, M. Key Eng. Mater. 1991, 61/62, 513. (4) Williams, R. A.; Peng, S. J.; Wheeler, D. A.; Morley, N. C.; Taylor, D.; Whalley, M.; Houldworth, D. W. Chem. Eng. Res. Des. A 1998, 76, 902. (5) Abrahamse, A. J.; van Lierop, R.; van der Sman, R. G. M.; van der Padt, A.; Boom, R. M. J. Membr. Sci. 2002, 204, 127. (6) Vladisavljevic´, G. T.; Williams, R. A. J. Colloid Interface Sci. 2006, 299, 396. (7) Bibette, J. J. Colloid Interface Sci. 1991, 147, 474. (8) Mason, T. G.; Bibette, J. Phys. ReV. Lett. 1996, 77, 3481. (9) Suzuki, K.; Shuto, I.; Hagura, Y. Food Sci. Technol. Int., Tokyo 1996, 2, 43. (10) Thorsen, T.; Roberts, E. W.; Arnold, F. H.; Quake, S. R. Phys. ReV. Lett. 2001, 86, 4163. (11) Nishisako, T.; Torii, T.; Higuchi, T. Lab Chip 2002, 2, 24. (12) Anna, S. L.; Bontoux, N.; Stone, H. A. Appl. Phys. Lett. 2003, 82, 364. (13) Xu, Q.; Nakajima, M. Appl. Phys. Lett. 2004, 85, 3726. (14) Link, D. R.; Anna, S. L.; Weitz, D. A.; Stone, H. A. Phys. ReV. Lett. 2004, 92, 054503.
devices allow one to generate monodisperse spherical and nonspherical droplets by appropriately controlling the flow conditions and channel geometries.10,14,16 Nonspherical droplets flowing inside microfluidic devices have useful applications as chemical and biological micromixers17,18 and microreactors.19,20 In addition, monodisperse nonspherical microparticles have been successfully prepared by solidifying or gelling the nonspherical droplets in the microfluidic devices.21-23 Potential applications of nonspherical microparticles include photonic materials, sensors, and microcarriers for drug delivery systems. However, a single microfluidic device usually has one channel for the to-be-dispersed phase, causing limited throughput capacity for droplets and microparticles. Our research group proposed microchannel (MC) emulsification for formulating monodisperse emulsions using a microfluidic device with MC arrays of unique geometry in the late 1990s.24 MC emulsification has been successfully used to formulate monodisperse emulsions with an average droplet diameter of 4-90 µm by simply forcing a to-be-dispersed phase through uniformly sized channels into a continuous phase.25,26 MC emulsification also has a unique droplet generation mechanism in which the interfacial tension, which is the dominant force on the micrometer scale, works as the driving force for droplet generation, enabling droplet generation from the channels based on spontaneous transformation of the to-be-dispersed phase at (15) Utada, A. S.; Lorenceau, E.; Link, D. R.; Kaplan, P. D.; Stone, H. A.; Weitz, D. A. Science 2005, 308, 537. (16) Xu, J. H.; Lou, G. S.; Li, S. W.; Chen. G. G. Lab Chip 2006, 6, 131. (17) Zheng, B.; Roach, L. S.; Ismagilov, R. F. J. Am. Chem. Soc. 2003, 125, 11170. (18) Song, H.; Tice, J. D.; Ismagilov, R. F. Angew. Chem., Int. Ed. 2003, 42, 768. (19) Shestopalov, I.; Tice, J. D.; Ismagilov, R. F. Lab Chip 2004, 4, 316. (20) Chan, E. M.; Alivisatos, A. P.; Mathies, R. A. J. Am. Chem. Soc. 2005, 127, 13854. (21) Xu, S.; Nie, Z.; Seo, M.; Lewis, P.; Kumacheva, E.; Stone, H. A.; Garstecki, P.; Weibel, D. B.; Gitlin, I.; Whitesides, G. M. Angew. Chem., Int. Ed. 2005, 44, 724. (22) Dendukuri, D.; Tsoi, K.; Hatton, A.: Doyle, P. S. Langmuir 2005, 21, 2113. (23) Seo, M.; Nie, Z.; Xu, S.; Lewis, P.; Kumacheva, E. Langmuir 2005, 21, 4773. (24) Kawakatsu, T.; Kikuchi, Y.; Nakajima, M. J. Am. Oil Chem. Soc. 1997, 74, 317. (25) Kobayashi, I.; Nakajima, M.; Nabetani, H.; Kikuchi, Y.; Shohno, A.; Satoh, K. J. Am. Oil Chem. Soc. 2001, 78, 797. (26) Sugiura, S.; Nakajima, M.; Seki, M. J. Am. Oil Chem. Soc. 2002, 79, 515.
10.1021/la0623329 CCC: $33.50 © 2006 American Chemical Society Published on Web 11/07/2006
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Figure 1. (a) Schematic illustrations of a silicon MC array plate and an MC array used to generate discoid droplets. The plate had a thickness of 0.5 mm. A center through-hole with a diameter of 1.5 mm was fabricated to supply the to-be-dispersed phase in the space between the MC array plate and the quartz glass plate. Four lines of MC arrays were fabricated near the contour lines of the plate surface. There is a sharp step over the channel exit. (b) Optical micrograph of the MC array (MCA-A) designated with a dotted line in (a). (c) Schematic illustration of the generation of discoid O/W droplets using an MC array. (d,e) Typical optical micrographs of successful generation of discoid O/W droplets from channels in MCA-A. Sudan IV was mixed with the to-be-dispersed oil phase for better visualization. (f) Size distribution of the discoid O/W droplets depicted in (e).
a very high energy efficiency.27 We have recently proposed highthroughput MC emulsification devices with microfabricated through-hole arrays (straight-through MCs).28,29 Previous MC
emulsification devices had a continuous-phase space over the channel exit much larger than the size of the resultant droplets, leading to the generation of only spherical droplets.24,28
(27) Sugiura, S.; Nakajima, M.; Iwamoto, S.; Seki, M. Langmuir 2001, 17, 5562.
(28) Kobayashi, I.; Nakajima, M.; Chun, K.; Kikuchi, Y.; Fujita, H. AIChE J. 2002, 48, 1639.
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Table 1. Dimensions of Silicon MC Arrays Used in This Study
no. MCA-A MCA-B MCA-C
channel total channel channel channel well equivalent channel width length height height diametera number [µm] [µm] [µm] [µm] [µm] [-] 27.2 32.2 10.2
199 199 39.8
5.0 5.0 1.9
9.8 9.8 4.6
8.4 8.7 3.2
100 100 484
a Channel equivalent diameter is defined as four times the crosssectional area divided by the wetted perimeter of the channel.
In this paper, we propose a novel technique for generating monodisperse emulsion droplets with a discoid shape by simply forcing a to-be-dispersed phase through an MC array into a shallow well filled with a continuous phase. The ratio of the well height to the channel height (hwell/hch, see Figure 1a) is a critical parameter for confining the generated droplets in the well. The size of the spherical droplets produced using previous MC emulsification devices generally exceeds the channel height by more than 3 times.24,28 The previous MC arrays for generating spherical droplets also have a deeply etched well whose height usually exceeds the channel height by more than 10 times.30 We therefore designed new MC arrays where the hwell/hch value is 2 to geometrically confine the droplets generated from the channels. We note that only confining the to-be-dispersed phase that passed through the channels is not sufficient to generate successfully monodisperse discoid droplets.31 The technique proposed in this paper can be used to control the size of the resultant discoid droplets using MC arrays with different dimensions and can generate oil-in-water (O/W) and W/O discoid droplets using surface-treated MC arrays. This paper also describes the coalescence stability of the discoid droplets generated using the MC arrays. The silicon MC array plate with its multilevel structure was microfabricated through repeated processes of photolithography and silicon dry etching (Figure 1a; Supporting Information). Figure 1b shows a microfabricated channel array with a shallow well over the channel exit. The dimensions of the MC arrays used in this study (MCAs-A, -B, and -C) are given in Table 1. The channels microfabricated in this study had a very narrow size distribution with a typical CV value of less than 1%, satisfying a prerequisite for a device for generating monodisperse droplets. The calculated hwell/hch values were 2.0 for MCAs-A and -B and 2.4 for MCA-C. We used the laboratory-scale setup for MC emulsification described elsewhere24 to generate O/W and W/O droplets. The microfabricated plane of the MC array plate was sealed by pressing it against a quartz-glass plate in the module, which is first filled with the continuous phase. Stable generation of monodisperse droplets can only be achieved when the continuous phase preferentially wets the channel surface.24,32 The O/W dropletgenerating experiments used a hydrophilic MC array plate and a glass plate, which were obtained after an oxygen plasma treatment. The W/O droplet-generating experiments used a (29) Kobayashi, I.; Mukataka, S.; Nakajima, M. Langmuir 2005, 21, 7629. (30) The deeply etched well in the previous MC emulsification devices can maintain a sufficient space for the continuous phase near the outlet of the MC array during emulsification operations, which is useful for achieving the stable generation of monodisperse spherical droplets from the channels. (31) When the step at the channel outlet is negligible (the ratio of the well height to the channel height is nearly 1), the to-be-dispersed phase that passed through the channels flows out continuously, and droplet generation from the channels does not occur. When the well depth is close to the resultant droplet diameter (the ratio of the well height to the channel height is typically 3 or more), mostly spherical droplets are generated from the channels. (32) Kawakatsu, T.; Tra¨ga˚rdh, G.; Tra¨ga˚rdh, Ch.; Nakajima, M.; Oda, N.; Yonemoto, T. Colloids Surf., A 2001, 179, 29.
hydrophobic MC array plate and a glass plate, which were obtained after silanization treatment using octadecyltriethoxysilane (LS-6970, Shin-Etsu Chemical Co., Ltd.), based on procedures in the published literature.24,33 The to-be-dispersed phase, pressurized by lifting the liquid chamber containing it, was introduced into the module through flexible tubing connected to the chamber. The to-be-dispersed phase was then forced to pass through the channels to generate droplets, as illustrated in Figure 1c. We observed the droplet generation from the channels using a CCD camera (KP-C550, Hitachi, Ltd.) or a high-speed CCD camera (FASTCAM-Rabbit-mini-2, Photoron, Ltd.) mounted on a microscope (MS-511B, Seiwa Kougaku Seisakusho, Ltd.). WinRoof software (Mitani Co., Ltd.) was used to determine the size distribution of the generated droplets by measuring the diameters of 100 droplets in the captured images. We first conducted droplet generation using MCA-A with refined soybean oil (viscosity η ) 50.4 mPa s) in 1.0 wt % sodium dodecyl sulfate (SDS) aqueous solution (η ) 0.98 mPa s) system. Figure 1d,e depicts a typical example of O/W droplet generation from the channels in MCA-A. The to-be-dispersed phase began to pass through the channel exit at a pressure (Pd) of 3.2 kPa and then grew with a distorted shape in the well. The to-be-dispersed phase that grew in the well was stably transformed into uniformly sized droplets without applying a forced crossflow of the continuous phase, suggesting that this droplet generation is driven by the interfacial tension effects reported by Sugiura et al.27 The generated droplets formed a mostly closepacked array of a single layer in the well. Figure 1f shows the size distribution of the generated droplets depicted in Figure 1e. Their average diameter (dav,dr) of 21.4 µm was larger than the well height of 9.8 µm, demonstrating that the generated O/W droplets have a discoid shape with circular interfaces at the top and bottom of the well. The average aspect ratio (dav,dr/hwell) of the discoid droplets generated in this case was 2.2. They had a narrow diameter distribution with a CV of 1.8%, confirming that they were monodisperse. Thus, Figure 1d-f demonstrates that the novel MC array proposed in this study is capable of generating monodisperse discoid droplets. We estimated the average volume of the discoid droplets as Vav,dr ) πdav,dr2hwell/4.34 The Vav,dr of the discoid droplets depicted in Figure 1e was estimated to be 3.5 pL, corresponding to the volume of a spherical droplet with a diameter of 18.9 µm. This droplet diameter exceeds the channel height by 3.8 times and the channel equivalent diameter (defined as four times the cross-sectional area divided by the wetted perimeter of the channel) by 2.2 times. The above ratios of the droplet size to the channel sizes are analogous to those for spherical droplets generated by MC emulsification, as reported in the literature.25,28 We next generated discoid droplets from the channels in MCA-A using silicone oil (η ) 4.6, 48.0, or 485 mPa s, ShinEtsu Chemical Co., Ltd.) as the to-be-dispersed phase and 1.0 wt % SDS aqueous solution as the continuous phase. Discoid O/W droplets of uniform sizes were stably generated from the channels for all the silicone oils (data not shown). The dav,dr values for the generated discoid droplets were 25.6 µm (η ) 4.6 mPa s), 22.8 µm (48.0 mPa s), and 25.9 µm (485 mPa s). Their narrow size distribution with a CV of less than 3% (Figure 2a-c) confirms that monodisperse discoid droplets were successfully obtained. The preceding results suggest that the novel MC array is applicable to the generation of monodisperse discoid (33) Sugiura, S.; Nakajima, M.; Ushijima, H.; Yamamoto, K.; Seki, M. J. Chem. Eng. Japan 2001, 34, 757. (34) Please note that this estimation regards the droplet shape as the column, that is, the real droplet volume may be a little smaller than Vav,dr.
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Figure 2. (a-c) Size distributions of the discoid O/W droplets generated using MCA-A for silicone oils with η of 4.6 mPa s (a), 48.0 mPa s (b), and 485 mPa s (c). The pressures applied to the to-be-dispersed phase were 3.1 kPa (a), 3.3 kPa (b), and 6.2 kPa (c). (d) Optical micrograph of fresh discoid droplets of silicone oil (η ) 48.0 mPa s). (e) Optical micrograph of 7-day-old discoid droplets of silicone oil (η ) 48.0 mPa s).
droplets using a to-be-dispersed phase with a wide viscosity range. The monodisperse discoid droplets of silicone oil (η ) 48.0 mPa s) generated using MCA-A (Figure 2d) were kept in the well at room temperature (20-25 °C) to evaluate their stability. During storage, the discoid droplets filled the well as a mostly close-packed array of two dimensions, and most of the neighboring droplets were in contact with each other. The curvature of their contacting interface (Figure 2d) caused a pressure differential across the interface (∆P) called the Laplace pressure, defined as ∆P ) (1/R1 + 1/R2)γ, where R1 and R2 are the local principal radii of the curvature of the contacting interface and γ is the interfacial tension at the contacting interface. The contacting interface of the discoid droplets is considered to be unstable from the viewpoint of the interfacial free energy, because their interfacial area is larger than that of spherical droplets with the same volume. However, the micrographs in Figure 2d,e indicate that the discoid droplets were still monodisperse 7 days after droplet generation. We also did not observe droplet coalescence or any change in droplet size during storage. Thus, our results in Figure 2d,e demonstrate that the monodisperse discoid droplets generated using the silicone oil/water/SDS system are stable against droplet coalescence. Nonspherical droplets generated using other microfluidic devices keep their shape and size for a limited period of several tens of minutes or less before they emerge from the outlet channel. The droplets collected from these microfluidic devices end up with a spherical shape. Figure 3a shows a micrograph of the generation of discoid droplets from the channels in MCA-C using silicone oil (η ) 48.0 mPa s) in a 1.0 wt % SDS aqueous solution system. Figure
3b shows the size distribution of discoid O/W droplets generated using MCA-C. Monodisperse discoid droplets with a dav,dr of 7.7 µm, a height of 4.6 µm, and a CV of 2.7% were stably generated from the channels in this case, forming a mostly close-packed array of a single layer in the well. Their diameter and height demonstrate that several-micrometer-sized discoid droplets can be successfully generated using the novel MC array. The estimated Vav,dr of the several-micrometer-sized discoid droplets was 0.21 pL, while a spherical droplet with this volume has a diameter of 7.4 µm. This droplet diameter exceeds the channel height by 3.9 times and the channel equivalent diameter by 2.3 times, which are similar to the ratios for the discoid droplets generated using MCA-A. We also generated W/O droplets from silanized channels in MCA-B using a mixture (η ) 5.9 mPa s) of 50 wt % aqueous solution containing 5.0 wt % sodium chloride and 50 wt % glycerol as the to-be-dispersed phase and a decane solution (η ) 1.0 mPa s) containing 3.0 wt % tetraglycerin monolaurate condensed ricinoleic acid esters (CR-310, Sakamoto Yakuhin Kogyo Co., Ltd.) as the continuous phase. The micrograph in Figure 4a demonstrates that W/O droplets of a uniform size were generated from the channels. The generated droplets, with a dav,dr of 30.1 µm and a height of 9.8 µm, had almost circular interfaces at the top and bottom of the well, demonstrating their discoid shape. Their CV value (3.1%) and the droplet size distribution (Figure 4b) also confirm their narrow size distribution. As a result, Figure 4 demonstrates that the novel silanized MC array enabled the generation of monodisperse discoid W/O droplets. Each active channel in the MC arrays produced monodisperse discoid droplets at maximum generation rates of 11.1 s-1 for
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Figure 3. (a) Optical micrograph of the generation of monodisperse discoid O/W droplets several microns in size using MCA-C. The pressure applied to the to-be-dispersed phase was 7.1 kPa. (b) Size distribution of the discoid O/W droplets depicted in (a).
MCA-A and 16.7 s-1 for MCA-C by controlling Pd.35 The single MC array plate with many channels used in this study has the potential to produce monodisperse discoid droplets at generation rates of up to 1100 s-1 for MCA-A and 8100 s-1 for MCA-C. Increasing the number of channels in a single MC array plate, an advance which is currently under development, is required to increase production of monodisperse discoid droplets. In conclusion, we have demonstrated a novel technique for generating geometrically confined droplets using MC arrays with a shallow well. The MC arrays developed in this study are capable of generating monodisperse discoid droplets of O/W and W/O types without applying a forced cross-flow of the continuous phase. Most of the neighboring discoid droplets were in contact with each other in the well; nevertheless, those consisting of a silicone oil/water/SDS system were stable, with no droplet coalescence or changes in the droplet size observed during storage. An MC array with several-micrometer-sized channels enabled the generation of monodisperse several-micrometer-sized discoid (35) We measured the droplet generation rate of the center channel in the MC array.
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Figure 4. (a) Optical micrograph of the generation of monodisperse discoid W/O droplets using MCA-B. The pressure applied to the to-be-dispersed phase was 1.9 kPa. Sudan IV was mixed with the continuous oil phase for better visualization. (b) Size distribution of the discoid W/O droplets depicted in (a).
droplets. Although each active channel produces monodisperse discoid droplets at a relatively low generation rate, an MC array plate composed of many parallel channels is useful for increasing productivity. This droplet generation device can be applied to the production of monodisperse nonspherical microparticles and microcapsules. Geometrically confined droplets and the array formed within the device may also have applications as chemical and biological microreactors and microcarriers. Acknowledgment. This work was supported by the Nanotechnology Project of the Ministry of Agriculture, Forestry and Fisheries of Japan, and by a grant from the Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientists, I.K.). We also thank Ms. Chieko Takahashi, National Food Research Institute, for her help with our experiments. Supporting Information Available: Description of the microfabrication process of an MC array plate and SEM micrograph of a microfabricated MC array. This material is available free of charge via the Internet at http://pubs.asc.org. LA0623329
