Ind. Eng. Chem. Res. 2002, 41, 4043-4047
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MATERIALS AND INTERFACES Preparation of Monodispersed Polymeric Microspheres over 50 µm Employing Microchannel Emulsification Shinji Sugiura,†,‡ Mitsutoshi Nakajima,*,† and Minoru Seki‡ National Food Research Institute (NFRI), 2-1-12, Kannondai, Tsukuba, Ibaraki 305-8642, Japan, and Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8654, Japan
Recently, we proposed microchannel (MC) emulsification, a novel method for making monodispersed emulsion with a coefficient of variation of less than 5%. In this study, we prepared monodispersed polymeric divinylbenzene microspheres (MS) exceeding 50 µm in diameter by MC emulsification and subsequent polymerization. Using two types of MC plates, we prepared MS with 86.7 µm on average diameters and 4.8% coefficients of variation, as well as MS with 69.0 µm on average diameters and 4.1% coefficients of variation. The MS diameter can be controlled by the terrace length. The MS prepared in this manner had as narrow a size distribution as did the MS prepared by seed polymerization. The effects of the applied pressures on the droplet diameter distributions during MC emulsification were investigated. At low applied pressures, the applied pressure did not affect the droplet diameter so much, and monodispersed emulsions were produced. Introduction Polymeric microspheres (MS) with uniform size distribution have been recognized as one of the most sophisticated materials in various industrial fields. Polymeric MS of 100 µm in diameter have been produced commercially by the suspension polymerization process. In this process, a monomer is dispersed in another liquid under the influence of shear force, which eventually results in a wide size distribution.1 The polymer particles must then be classified when they are to be used for sophisticated purposes such as ionexchange resins and packing materials for column chromatography. Polymeric MS with diameters from 0.01 to 1 µm can be prepared by miniemulsion,2 emulsion,3 and soap-free emulsion4 polymerization and the seed polymerization method.5-7 Monodispersed polymeric MS have been successfully prepared by seed polymerization. However, synthesis of monodispersed polymeric MS with diameters exceeding several micrometers is not so easy. Extremely monodispersed polymeric MS of more than 10 µm and up to a maximum of 100 µm in diameter can be obtained by adopting a unique seeded emulsion polymerization, one referred to as the two-stage swelling technique developed by Ugelstad et al.,8 and the other, well-known as the synthesis method used on space shuttles, the NASA project promoted by Vanderhoff et al.9 Membrane emulsification is a promising technique for producing emulsions with narrow size distributions.10-12 * To whom correspondence may be addressed. Tel: +81-2987997. Fax: +81-298-8122. E-mail:
[email protected]. † National Food Research Institute. ‡ The University of Tokyo.
The emulsions are produced by pressurizing a dispersed phase into a continuous phase through a microporous membrane, and the emulsion droplet size is controlled by the membrane pore size. This technique can be used to prepare emulsions without high mechanical stress at lower energy input than conventional emulsification techniques.13 By use of this technique, polymeric MS with a coefficient of variation greater than 10% have been successfully prepared.14-17 However, it is difficult to produce monodispersed emulsions over a 10 µm scale since the pore size distribution of the membrane is rather wide in this range. Recently, we proposed a novel method for making monodispersed emulsion droplets from a microfabricated channel array.18-20 This emulsification technique is called microchannel (MC) emulsification and has been employed to produce emulsions with a coefficient of variation of smaller than 5%.20 Emulsions with a droplet size of 5-30 µm were prepared using the MC emulsification technique.21,22 The droplet diameter is determined by the MC geometry.23 This emulsification technique exploits the interfacial tension, which is the dominant force on a micrometer scale, as driving force for droplet formation.20 During droplet formation, the distorted dispersed phase spontaneously transforms into spherical droplets by interfacial tension. The energy input for MC emulsification is much lower than that of the conventional emulsification technique because droplet formation from MC is based on spontaneous transformation.20 We have applied it to preparing several types of oil-in-water emulsions, water-in-oil emulsions,24,25 and lipid microparticles.21 In previous study, we also applied it to preparing polymeric MS.26 The prepared polymeric MS had average diameters of 3.49.2 µm and coefficients of variation of 5.7-7.4%. The
10.1021/ie0201415 CCC: $22.00 © 2002 American Chemical Society Published on Web 07/16/2002
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coefficients of variation of prepared MS were larger than the emulsions composed of natural oils shown in other studies,20-22 because the wetting of the MC surface with the dispersed phase affected the emulsification behavior. In this study, we employed MC emulsification to prepare monodispersed polymeric MS exceeding 50 µm in diameter. MCs with large dimensions were designed to produce emulsions with large droplets. Monodispersed monomer emulsions were prepared by MC emulsification and then polymerized by suspension polymerization. The morphology of the prepared polymeric MS was investigated with scanning electron microscope (SEM) observation. The effects of the applied pressures on the droplet diameter distributions were also investigated. Experimental Section Materials. Divinylbenzene (DVB) was obtained from Sankyo Chemical Ind., Ltd. (Tokyo, Japan), and used as a monomer without any purification. (DVB) was commercial grade and a mixture of 55-60 wt % isomeric DVB, 35-40 wt % ethyl vinylbenzene, and other compounds. Benzoyl peroxide (BPO) was obtained from NOF Corp. (Tokyo, Japan) and used as an initiator. BPO was commercial grade containing 25 wt % moisture. Poly(vinyl alcohol) (PVA) was obtained from The Nippon Synthetic Chemical Industry Co., Ltd. (Osaka, Japan), and used as a stabilizer during the polymerization process. PVA was commercial grade with 1500-degree polymerization and 86.5-89.0% saponification value. Sodium dodecyl sulfate (SDS) was purchased from Wako Pure Chemical Ind., Ltd. (Osaka, Japan), and used as the surfactant for emulsification. MC Emulsification. The laboratory-scale apparatus for MC emulsification was described previously.18,19 Figure 1 shows the experiment setup used in this study and schematic flows of the dispersed oil phase and continuous water phase in the MC module. The experiment setup consists of an MC module, a silicon MC plate, a microscope video system, a liquid chamber supplying the dispersed oil phase, and a microfeeder supplying the continuous water phase. A cross-flow-type MC plate was adopted for continuous emulsification and recovery.19 The emulsification behavior was observed through a glass plate using the microscope video system. The observed images were extracted with an inverted metallographic microscope (MS-511B; Seiwa Optical Industrial Co., Saitama, Japan), detected by using a charge-coupled device (CCD) camera (HV-C20M, Hitachi, Tokyo, Japan), and recorded by a VHS video recorder (WV-ST1, Sony Corporation, Tokyo, Japan) with a total magnification of ×1000. The cross-flow silicon MC plates for continuous emulsification were newly designed. They were fabricated by a process of photolithography and orientation-dependent etching.27 Figure 2 shows the schematics of MC plates used in this study. The silicon MC plates were 22.5 mm × 8 mm and were manufactured with two 1.5 mm diameter holes as the inlet and outlet of the continuous phase. Two terrace lines with a length of 14 mm were fabricated on the MC plate. In the present study, two MC plates (MC-A and MC-B) were used for preparing emulsions of different sizes. Table 1 shows the dimensions of the two MC plates. Each MC plate has 10 and 30 channels along each terrace line, and 20 and 60 channels in total. After fabricating the MC plates, we oxidized their surfaces and treated them with 0.1 mol/L nitric acid
Figure 1. Experiment setup and schematic flows in MC module.
Figure 2. Cross-flow silicon MC plate: (A) schematic of MC plate; (B) enlargement of MC; (C) microscope photograph of MC.
before use. MC plates were sufficiently hydrophilic to be wetted with water. The MC module was initially filled with the continuous phase. The monomer phase, which was pressurized by the nitrogen gas pressure, entered the space between the silicon MC plate and the glass plate, and droplets were formed from the MC. The prepared monomer emulsions were recovered by a continuous phase flow.
Ind. Eng. Chem. Res., Vol. 41, No. 16, 2002 4045 Table 1. Dimensions of the Cross-Flow Type MC Plates MC type
no. of channels
MC width (µm)
MC depth (µm)
terrace length (µm)
MC-A MC-B
60 20
30 30
16 16
98 240
Polymerization. After the MC emulsification, we mixed the monomer emulsions with the 4 wt % PVA solutions. The final PVA concentration was 2 wt %. The mixtures were heated to a reaction temperature, normally 90 °C, and polymerized for 2 h. After polymerization, polymeric MS were recovered as precipitate, washed with water three times, and dried at 50 °C. Analytical Method. The number-average diameters and coefficients of variation of the prepared emulsions and MS were determined from pictures of 100 droplets and particles taken with the microscope video system described above. The coefficient of variation is defined as follows:
CV ) (σ/Dp) × 100
(1)
where CV is the coefficient of variation [%], Dp is the number-average diameter (µm), and σ is the standard deviation of the diameter (µm). Winroof (Mitani Corporation, Fukui, Japan) software was used to analyze the captured pictures. General features of the polymeric MS were observed with an SEM (JSM-5600LC, JEOL Ltd., Tokyo, Japan). The interfacial tension in each system was measured using a fully automatic interfacial tensiometer (PD-W, Kyowa Interface Science Co., Ltd., Saitama, Japan). Results and Discussion DVB with 2 wt % BPO was used as the dispersed oil phase, and SDS aqueous solution was used as the continuous phase. Surfactant concentrations exceeding the critical micelle concentration (cmc) were preferable for stable emulsification. The cmc of sodium dodecyl sulfate (SDS) was 0.2%, as determined by interfacial tension measurement (data not shown). Therefore, a 0.2% SDS concentration was adopted. MC emulsification was carried out using the two MC plates as shown in Table 1. MC emulsification was performed at 25 °C. The continuous phase was supplied by a microfeeder at a flow rate of 1.0 mL/h. The dispersed phase was pressurized into the MC module by lifting the liquid chamber filled with the dispersed phase. The applied pressure was calculated from the head difference between liquid chamber and emulsion outlet. Figure 3 shows microscope photographs of the MC emulsification process using MC-A and MC-B. The pressures applied to the dispersed phase were 1.1 kPa for MC-A and 1.0 kPa for MC-B. The diameters of the 100 droplets were measured for each MC plate. The average diameters and coefficients of variation of the emulsion prepared using MC-A were 74.9 µm and 2.8%, those for MC-B were 90.2 µm and 2.3%. The monodispersed emulsions were prepared. The DVB emulsions prepared in a previous study had average diameters of 10.0 and 4.2 µm, coefficients of variation of 4.4 and 9.1%.26 The DVB emulsions prepared in this study had larger droplet sizes and narrower size distributions than the DVB emulsions in the previous study. The previous study demonstrated that the wetted MC produced large droplets during emulsification process and it led the large coefficients of
Figure 3. Microscope photograph of the MC emulsification process in the system: DVB with 2% BPO and 0.2% SDS aqueous solution using MC-A (A) and MC-B (B).
variation.25 This phenomenon affects the emulsification behavior more significantly in smaller scales, which was optically observed in previous study.26 The emulsions prepared in this study had large droplet sizes compared to the previous study. Therefore, the emulsification behavior was not affected by the wetting, which resulted in the narrow diameter distributions. The monodispersed emulsions prepared by MC emulsification were recovered from the module and then mixed with the PVA solution, which was used as a stabilizer during polymerization. The emulsions were polymerized at 90 °C for 2 h, and then the polymeric MS suspensions were obtained. The prepared MS were washed with water three times. The washing process may remove particles smaller than 1 µm, which are often prepared in suspension polymerization as byproducts. The washed MS were dried at 50 °C and observed with SEM. Figure 4 shows the SEM photographs of the polymeric MS. The prepared polymeric MS had regularsized spherical shapes as shown in Figure 4. The diameters of the 100 MS were measured for each MC plate. Figure 5 shows the diameter distributions of the polymeric MS. The average diameters and coefficients of variation for MC-A were 69.0 µm and 4.1% and those for MC-B were 86.7 µm and 4.8%. The monodispersed MS were prepared. The MS thus prepared had as narrow a size distribution as did the MS prepared by seed polymerization. For each MC, the coefficients of variation increased from 2-3% to 4-9% after polymerization. The average MS diameters decreased by 4-8% after polymerization. One of the reasons of decrease in size is that the density of polymer is higher than that of the monomer liquid. Another reason is the solubilization and evaporation from the emulsion. The micelles composed of SDS solubilized DVB and solubilized DVB were evaporated from the air-water interface. The phenomena significantly affect in smaller size because of its high surfacevolume ratio, which is in accordance with the experimental results. The decrease in size is not significant for polymerization of larger MS than smaller MS
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Figure 6. Effect of applied pressure on the droplet diameter distribution using different MC plates: average diameter for MC-A (O), and MC-B (0); coefficient of variation (CV) for MC-A (b), and MC-B (9). Over 1.5 kPa pressure, the droplet diameter significantly increased with increasing the applied pressure, and ultimately the dispersed phase flowed out continuously from the channels. Figure 4. SEM image of polymeric MS prepared using MC-A (A) and MC-B (B).
significant for smaller emulsions because of their high surface-volume ratio. This makes the emulsions unstable during recovery and polymerization, especially for small emulsions. On comparison of two MC plates, larger MS were prepared using a MC with longer terraces. Preparation of monodispersed MS with large droplets up to 90 µm was possible using MC-B. From the point of droplet formation, preparation of larger droplets may be possible if a longer and deeper MC had been used. However, it was difficult to fabricate MC plates with MCs deeper than 16 µm and terraces exceeding 240 µm by the wet etching process because of difficulty in the resist coating process. Different etching processes, such as reactiveion etching, may enable the fabrication of larger and deeper MC. The effect of the applied pressure on emulsification behavior was also studied. Figure 6 shows the effect of the applied pressure on the droplet diameter distribution for each MC plate. The diameters of 100 droplets were measured for each pressure. The breakthrough pressures for each of the MC plates were similar values (0.67 for MC-A and 0.80 kPa for MC-B) and seem to be independent of terrace length. Breakthrough pressure corresponds to the Laplace pressure between the oil phase and water phase in the MC as shown in the following equation28
Pbt ) Figure 5. Diameter distribution of polymeric MS prepared using MC-A (A) and MC-B (B).
described in the previous study (10-20%),26 because the solubilization affects significantly in smaller scale. The large MS in this study had narrower size distributions than those of small MS in the previous study for several reasons. One is the monodispersity of the obtained emulsion. Producing a small emulsion of narrow size distribution is more difficult than producing a large emulsion because the wetting more significantly affected production of small emulsions than that of large emulsions. Other reasons are that the effects of Ostwald ripening, solubilization, and evaporation in emulsion are
4γ cos θ d
(2)
where Pbt is the breakthrough pressure, γ is the interfacial tension, θ is the interface contact angle with the wall of the channel, and d is the channel diameter. Equation 2 indicates that the breakthrough pressure depends on the MC width and depth and is independent of the terrace length. This is consistent with our experiment results. At the pressures from 0.67 to 1.34 kPa for MC-A and 0.80 to 1.43 kPa for MC-B, the applied pressure did not affect the droplet diameter so much. The coefficients of variation were 2-4%, and monodispersed emulsions were prepared in these pressure ranges. Droplet formation for MC emulsification is caused by interfacial
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tension, which works to transform the distorted dispersed oil phase on the terrace into spherical droplets.20 In these pressure ranges, the interfacial tension is dominant compared to the other forces such as inertial force and drag force of the continuous phase. The dominant interfacial tension enables the dispersed phase to detach from the terrace at intervals. It led to formation of monodispersed droplet even though the droplet formation rate increased with the applied pressure. Over 1.5 kPa pressure, the droplet diameters significantly increased with increasing applied pressure, and ultimately the dispersed phase flowed out continuously from the channels. At these pressure ranges, the interfacial tension, which causes the transformation of the dispersed phase, is not sufficiently strong compared to the other forces. It leads the larger polydispersed emulsion droplets (data not shown). The droplet diameter may be determined by the balance between the interfacial tension, the inertial force, and the drag force of the continuous phase. From the above discussion, it is possible to prepare monodispersed MS with diameters of about 100 µm using MC emulsification. Preparing monodispersed emulsions with droplets exceeding 100 µm was difficult because of the difficulty in fabricating MC plates. Monodispersed MS with diameters of less than several micrometers can be prepared by other processes, such as miniemulsion, soap-free emulsion, and seed polymerization. These facts indicate MC emulsification has advantages for preparing monodispersed polymeric MS in the range from several micrometers to 100 µm because of its simplicity. This technique is expected to be useful for preparing various polymeric MS requiring excellent monodispersity. Conclusion MC emulsification was applied to prepare monodispersed poly-DVB MS. Monodispersed poly-DVB MS were prepared by MC emulsification and subsequent polymerization. The monodispersed emulsions composed of DVB and SDS aqueous solutions were prepared by MC emulsification. The average diameters and coefficients of variation of the emulsion droplets for MC-A were 74.9 µm and 2.8%, those for MC-B were 90.2 µm and 2.3%. The prepared emulsions were recovered and polymerized. The average diameters and coefficients of variation of MS for MC-A were 69.0 µm and 4.1%, those for MC-B were 86.7 µm and 4.8%. The prepared polymeric MS had a narrow size distribution equivalent to that of polymeric MS prepared by seed polymerization. The MS had spherical shapes. The MS diameter can be controlled by the terrace. MC emulsification has advantages for preparing monodispersed polymeric MS in the range from several micrometers to 100 µm because of its simplicity. Acknowledgment This work was supported by the Nanotechnology Project of Ministry of Agriculture, Forestry and Fisheries, Japan, and Program for Promotion of Basic Re-
search Activities for Innovative Biosciences (MS-Project). We thank Mr. Katsunori Mukai, Sekisui Chemical Co., Ltd., for advice on our experiment. We also thank Ms. Mariko Yoshioka, National Food Research Institute, for helping with our experiment. Literature Cited (1) Omi, S.; Taguchi, T.; Nagai, M.; Ma, G. H. J. Appl. Polym. Sci. 1997, 63, 931-942. (2) Landfester, K.; Willert, M.; Antonietti, M. Macromolecules 2000, 33, 2370-2376. (3) Echevarrı´a, A.; Leiza, J. R.; de la Cal, J. C.; Asua, J. M. AIChE J. 1998, 44, 1667-1679. (4) Andre´, A.; Henry, F. Colloid Polym. Sci. 1998, 276, 10611067. (5) Ugelstad, J.; Mørk, P. C.; Kaggerud, K. H.; Ellingsen, T.; Berge A. Adv. Colloid Interface Sci. 1980, 13, 101-140. (6) Okubo, M.; Shiozaki, M.; Tsujihiro, M.; Tsukuda, Y. Colloid Polym. Sci. 1991, 269, 222-226. (7) Okubo, M.; Kanaida, K.; Fujimura, M. Colloid Polym. Sci. 1991, 269, 1257-1262. (8) Ugelstad, J.; Kaggerud, K. H.; Hansen, F. K.; Berge, A. Makromol. Chem. 1979, 180, 737-744. (9) Vanderhoff, J. W.; El-Aasser, M. S.; Micale, F. J.; Sudol, E. D.; Tseng, C.-M.; Silwanowicz, A.; Cornfeld, D. M.; Vicente, F. A. J. Dispersion Sci. Technol. 1984, 5, 231. (10) Nakashima, T.; Shimizu, M.; Kukizaki, M. Key Eng. Mater. 1991, 61 & 62, 513-516. (11) Joscelyne, S. M.; Tra¨gårdh, G. J. Membr. Sci. 2000, 169, 107-117. (12) Abrahamse, A. J.; van der Padt, A.; Boom, R. M.; de Heij, W. B. C. AIChE J. 2001, 47, 1285-1291. (13) Schro¨der, V.; Schubert, H. Colloids Surf., A 1999, 152, 103-109. (14) Omi, S.; Katami, K.; Yamamoto, A.; Iso, M. J. Appl. Polym. Sci. 1994, 51, 1-11. (15) Omi, S. Colloids Surf., A 1996, 109, 97-107. (16) Yoshizawa, H.; Ohta, H.; Maruta, M.; Uemura, Y.; Ijichi, K.; Hatate, Y. J. Chem. Eng. Jpn. 1996, 29, 1027-1029. (17) Omi, S.; Katami, K.; Taguchi, T.; Kaneko, K.; Iso, M. J. Appl. Polym. Sci. 1995, 57, 1013-1024. (18) Kawakatsu, T.; Kikuchi, Y.; Nakajima, M. J. Am. Oil Chem. Soc. 1997, 74, 317-321. (19) Kawakatsu, T.; Komori, H.; Nakajima, M.; Kikuchi, Y.; Yonemoto, T. J. Chem. Eng. Jpn. 1999, 32, 241-244. (20) Sugiura, S.; Nakajima, M.; Iwamoto, S.; Seki, M. Langmuir 2001, 17, 5562-5566. (21) Sugiura, S.; Nakajima, M.; Tong, J.; Nabetani, H.; Seki, M. J. Colloid Interface Sci. 2000, 227, 95-103. (22) Kobayashi, I.; Nakajima, M.; Nabetani, H.; Kikuchi, Y.; Shohno, A,; Satoh, K. J. Am. Oil Chem. Soc. 2001, 78, 797-802. (23) Sugiura, S.; Nakajima, M.; Seki, M. Langmuir 2002, 18, 3854-3859. (24) Kawakatsu, T.; Tra¨gårdh, G.; Tra¨gårdh, C.; Nakajima, M.; Oda, N.; Yonemoto, T. Colloids Surf., A 2001, 179, 29-37. (25) Sugiura, S.; Nakajima, M.; Ushijima, H.; Yamamoto, K.; Seki, M. J. Chem. Eng. Jpn 2001, 34, 757-765. (26) Sugiura, S.; Nakajima, M.; Itou, H.; Seki, M. Macromol. Rapid Commun. 2001, 22, 773-778. (27) Kikuchi, Y.; Sato, K.; Ohki, H.; Kaneko, T. Microvasc. Res. 1992, 44, 226-240. (28) Atkins, P. W. Physical Chemistry; Oxford University Press: Oxford, 1990.
Received for review February 15, 2002 Revised manuscript received May 13, 2002 Accepted June 5, 2002 IE0201415
