Article pubs.acs.org/Langmuir
Microfluidic Production of Semipermeable Microcapsules by Polymerization-Induced Phase Separation Bomi Kim,† Tae Yoon Jeon,† You-Kwan Oh,‡ and Shin-Hyun Kim*,† †
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea ‡ Biomass and Waste Energy Laboratory, Korea Institute of Energy Research (KIER), Daejeon, 305-343, Republic of Korea S Supporting Information *
ABSTRACT: Semipermeable microcapsules are appealing for controlled release of drugs, study of cell-to-cell communication, and isolation of enzymes or artificial catalysts. Here, we report a microfluidic strategy for creating monodisperse microcapsules with size-selective permeability using polymerization-induced phase separation. Monodisperse water-in-oilin-water (W/O/W) double-emulsion drops, whose ultrathin middle layer is composed of photocurable resin and inert oil, are generated in a capillary microfluidic device, and irradiated by UV light. Upon UV illumination, the monomers are photopolymerized, which leads to phase separation between the polymerized resin and the oil within the ultrathin shell. Subsequent dissolution of the oil leaves behind regular pores in the polymerized membrane that interconnect the interior and exterior of the microcapsules, thereby providing size-selective permeability. The degree of phase separation can be further tuned by adjusting the fraction of oil in the shell or the affinity of the oil to the monomers, thereby enabling the control of the cutoff value of permeation. High mechanical stability and chemical resistance of the microcapsules, as well as controllable permeability and high encapsulation efficiency, will provide new opportunity in a wide range of applications.
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INTRODUCTION Microcapsules composed of liquid core and dense solid membranes enable the stable storage of active ingredients or materials in the liquid core without leakage. The dense membrane does not allow diffusion of material through it, thereby completely isolating the interior of the capsule from surrounding environment. Such impermeable membranes are useful for microencapsulation of self-healing agents and display pigments.1−3 The dense membranes can be further functionalized to be degraded or ruptured only at specific environment.4−7 Such smart microcapsules are appealing for sustained or stimuli-triggered release of drugs and nutrients; for example, microcapsules whose membranes are designed to be selectively degraded in a basic condition can deliver their encapsulants to the intestine while retaining them at the stomach.8 The membrane can be also functionalized by forming uniform voids. Such a porous membrane allows the diffusion of materials smaller than the void, while excluding larger materials, thereby providing size-selective permeability.9,10 Semipermeable microcapsules are particularly valuable for multicatalyst systems and immunoisolation of cells.11−13 However, there are few methods to create semipermeable microcapsules, although various approaches have been intensively developed to make semipermeable planar membranes for separation processes.14,15 Furthermore, conventional approaches to produce semipermeable microcapsules, such as layer-by-layer deposition technique with colloidal templates, © 2015 American Chemical Society
lack controllability of permeability and efficiency of encapsulation.16,17 To overcome such shortcomings and achieve high uniformity of capsule composition, droplet-based microfluidic approaches have been employed.18,19 Microfluidic techniques have enabled the production of double-emulsion drops, dropsin-drops, which provide useful templates to produce microcapsules due to their intrinsic core−shell geometry,20−22 where the liquid middle layer can be transformed into a semipermeable solid membrane.23,24 For example, evaporation of the middle phase, which contains nanoparticles, produces a spherical shell of particle aggregates, thereby forming regular pores in the interstices of the nanoparticles.23 As an alternative, polymer solution containing small water drops can be used as the middle phase to produce pores in the polymer membrane.24 However, both approaches have intrinsic limitations: the nanoparticle membrane is too fragile to use for practical applications, and the polymerized shell has irregular or isolated pores, resulting in an uncontrolled cutoff value of permeation. To overcome such limitations, we recently employed phase separation of two immiscible polymers in the middle layer of the double-emulsion drops and selectively remove one polymer to produce regular pores in the membrane.25 However, usage of toxic organic solvents is inevitable to dissolve binary polymers Received: March 26, 2015 Revised: May 14, 2015 Published: May 28, 2015 6027
DOI: 10.1021/acs.langmuir.5b01129 Langmuir 2015, 31, 6027−6034
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Figure 1. (a) Schematic illustration of the microfluidic capillary device for production of double-emulsion drops with ultrathin shell and in situ polymerization of the shells. (b) Optical microscope image showing generation of monodisperse double-emulsion drops. (c,d) Optical microscope images showing double-emulsion drops (c) before and (d) after UV illumination. Inset of panel d shows indented capsules.
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in the middle phase. Furthermore, selective removal of one polymer after phase separation entails the additional usage of washing solvents, which are sometimes critical for bioactive or delicate encapsulants, thereby potentially limiting their applications. In this paper, we report a microfluidic approach for creating semipermeable microcapsules with a controlled cutoff value of permeation by employing polymerization-induced phase separation in the middle layer of the double-emulsion templates. With a capillary microfluidic device, monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops are prepared with ultrathin shells of a homogeneous mixture of photocurable resins and inert oil. Upon UV illumination of the drops, the resins confined in the ultrathin shell are polymerized, leading to their phase separation from the inert oil. Subsequent removal of the inert oil leaves behind regular voids in the capsule membrane, which interconnect the interior and the exterior of the capsules, thereby providing selective permeability; the inert oil, which is the pore generator, or porogen, can be removed by washing with either polar solvents or water. The size of the pores and therefore the cutoff value of permeation is determined by the degree of phase separation during polymerization, which can be controlled by adjusting the fraction of porogen in the middle phase or affinity of the porogen to the resin. The resulting microcapsules provide high mechanical durability and chemical resistance, as well as sizeselective permeability, due to the formation of a cross-linked monolithic matrix in the membrane.
EXPERIMENTAL SECTION
Materials. For the innermost and continuous phase, 10 wt/wt % aqueous solution of poly(vinyl alcohol) (PVA, Mw 13 000−23 000, Sigma-Aldrich) is used. For the middle phase, a ternary mixture of glycidyl methacrylate (GMA, Sigma-Aldrich), ethoxylated trimethylolpropane triacrylate (ETPTA, Sigma-Aldrich), and 1-decanol (SigmaAldrich) containing 1 wt % of 2,2-dimethoxy-1,2-diphenylethanone (Irgacure 651, Sigma-Aldrich) is used; a mixing ratio of GMA, ETPTA, and 1-decanol is typically set to be 51:34:15 in weight ratio, and the fraction of 1-decanol is further adjusted to control the porosity of the membrane while maintaining the ratio of GMA to ETPTA as 3:2. Butyl acetate (Sigma-Aldrich) is used instead of 1-decanol to make nanopores. To estimate the cutoff value of permeation and permeability, we employ red-fluorescent polystyrene (PS) particles with 217 nm diameter (Polyscience, Inc.), rhodamine 6G (SigmaAldrich), rhodamine B isothiocyanate (RITC)-tagged dextran (Mw = 10 000 g/mol, Sigma-Aldrich), fluorescein isothiocyanate (FITC)tagged dextran with five different molecular weights (Mw = 20 000 g/ mol, Mw = 70 000 g/mol, Mw = 150 000 g/mol, Mw = 500 000 g/mol, and Mw = 2 000 000 g/mol, Sigma-Aldrich). Preparation of Microfluidic Device. Two cylindrical capillaries (1B100F-6, World Precision Instruments, Inc.) are tapered by micropipette puller (P97, Sutter Instrument) to have 10 μm aperture. One of them is carefully sanded to have a 75-μm-orifice and treated with octadecyltrimethoxysilane (Sigma-Aldrich) to render it hydrophobic, whereas the other is sanded to have a 140-μm-orifice and treated with 2-[methoxy(polyethyleneoxy)propyl] trimethoxysilane (Gelest, Inc.) to render it hydrophilic. These two cylindrical capillaries are coaxially assembled within a square capillary (OD 1.5 mm, ID 1.05 mm, Atlantic International Technologies, Inc.) to have separation of 78 μm. A small tapered capillary is inserted into the untapered opening of the hydrophobic capillary to inject innermost fluids through the hydrophobic cylindrical capillary. 6028
DOI: 10.1021/acs.langmuir.5b01129 Langmuir 2015, 31, 6027−6034
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Figure 2. (a) Schematic illustration of production of semipermeable microcapsules through phase separation and removal of porogen. (b) Optical microscope image showing semipermeable microcapsules. (c,d) SEM images of dried microcapsules. (e) SEM image showing membrane crosssection which has regular pores. Inset of panel e shows surface pores. Generation of Double-Emulsion Drops and Photopolymerization. The volumetric flow rates are controlled by syringe pumps (Legato 100, KD Scientific). The production of double-emulsion drops is observed with an inverted optical microscope (Eclipse TS100, Nikon) equipped with a high speed camera (Phantom v7.3, Vision Research Inc.). The emulsion drops are collected in a glass dish containing an aqueous solution of 2 wt/wt % PVA and 40 mM NaCl. We illuminate the drops, in situ or off-chip, with UV light at an intensity of 2 W/cm2 using a fiber-coupled spot UV system (Inocure 100N, Lichtzen Co., Ltd.) to polymerize GMA and ETPTA. The porogen is selectively removed either by washing three times with methanol and acetone or by washing 10 times with distilled water. Characterization of Semipermeable Microcapsules. Scanning electron microscope (SEM, S-4800, Hitachi) is used to observe the surface and cross-section of the microcapsule membranes; microcapsules are cleaved with a razor blade for cross-section. To estimate the cutoff value of permeation for the microcapsules and show selective permeability, we disperse the microcapsules into a binary aqueous mixture of fluorescent dye molecules or colloids. After 24 h of incubation, we visualize the probes with a laser scanning confocal microscope (LSM 5 PASCAL, Carl Zeiss). To estimate the permeability, we take time-lapse images of microcapsules with a confocal microscope as soon as they are directly dispersed in 2.5 × 10−3 M aqueous solution of FITC-tagged dextran.
a ternary mixture of GMA, ETPTA, and 1-decanol through the hydrophobic cylindrical capillary, which then flow along the hydrophobic capillary channel simultaneously; flow rates of the innermost and middle phases are typically set to be 200 μL/h and 150 μL/h, respectively. Within the hydrophobic cylindrical capillary, the innermost aqueous phase forms a train of plug-like drops without contacting the wall, while the middle oil phase flows along the wall due to its higher affinity to the hydrophobic capillary, as shown in Figure S1a of the Supporting Information.26,27 As the plug-like drops arrive at the tip of hydrophobic capillary, they are emulsified into the continuous phase of 10 wt/wt % aqueous solution PVA in a dripping mode. The aqueous continuous phase, which is injected through the interstices between the hydrophobic cylindrical capillary and the square capillary typically at flow rate of 2500 μL/h, is strongly focused into the orifice of the hydrophilic counter capillary, exerting a high drag force on the growing drop at the tip of the hydrophobic injection capillary. This leads to the breakup of the interface and therefore the formation of W/O/W double-emulsion drops, as shown in Figure 1b and Movie S1 (SI File: la5b01129_si_002.avi) of the Supporting Information; the middle layer is too thin to observe with the optical microscope. The resultant drops flow through the hydrophilic capillary and are then collected in a glass dish containing an aqueous solution of 2 wt/wt % PVA and 40 mM NaCl, which has the same osmolarity of the innermost phase but a lower density. This enables the slow sedimentation of the double-emulsion drops while preventing transport of water molecules through the middle layer. Although the oil phase between neighboring
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RESULTS AND DISCUSSION Double-Emulsion Drops with Ultrathin Shell. To generate a double-emulsion template whose middle layer is ultrathin, we use an emulsification of core−sheath flow in a capillary microfluidic device, as schematically illustrated in Figure 1a.26 To form the core−sheath flow, we inject 10 wt/wt % aqueous solution PVA through a small tapered capillary and 6029
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Figure 3. (a−d) SEM images showing surface morphologies of microcapsules made from middle oil phase with (a) 0 wt/wt %, (b) 10 wt/wt %, (c) 15 wt/wt %, and (d) 20 wt/wt % porogen of 1-decanol. (e) Influence of porogen fraction on pore size and its distribution.
enough interaction parameter between the monomers and 1decanol makes a homogeneous mixture before polymerization.30,31 Above certain value of N, known as a gel point, the growing polymers become solid and phase-separated from 1-decanol. The polymers in solid domains are further crosslinked, eventually forming monolithic structures with consistently sized pores which are occupied by the liquid porogen. In particular, because polymerization is nearly completed within one second under UV irradiation, phase separation also occurs within the short time, thereby inducing local phase separation instead of global separation. During the polymerization, spherical double-emulsion drops are transformed to spherical microcapsules with small indentations, as shown in Figure 1d, where drops are illuminated by UV for one second after they are collected. In general, microcapsules experience such a buckling when inner fluid is pumped out through constant volume of membrane; for example, osmotic pressure difference can cause outward flux through membrane and buckling.29 However, there is no osmotic pressure difference and negligible Laplace pressure difference across the shell of double-emulsion drops. Moreover, the buckling occurs within very short time, which does not allow the liquid flux through the shell. Instead, microcapsules might experience the buckling when the surface area of the shell is increased while no change in core volume. Therefore, we attribute the indentation to the sudden expansion of the shell volume during phase separation.
plug-like drops in the hydrophobic capillary produces single oil drops at the tip, as shown in Figure S1c, the double-emulsion drops can be easily separated from the oil drops by exploiting their density and size difference. The resultant monodisperse double-emulsion drops with ultrathin middle layers are shown in Figure 1c; the average diameter of the drops is 84 μm and the coefficient of variation is less than 3%. The resultant double-emulsion drops have ultrathin shells, which provide high stability on the drop due to strong lubrication resistance in the middle layer.28,29 In addition, when the middle layer is solidified into the membrane with interconnected pores, the ultrathin membrane can provide a short path for diffusion, thereby facilitating fast transport of material through the pores. Polymerization-Induced Phase Separation. We irradiate the drops, in situ or off-chip, with UV light to polymerize GMA and ETPTA in the ultrathin middle layer. In-situ irradiation immediately after the drops enter the collection liquid provides the continuous polymerization, while off-chip irradiation, after drops are all collected, enables the observation of the drop transformation during one-shot polymerization; both methods result in the same capsule structure. Upon irradiation, the photoinitiators form free radicals which react with monomers. As the propagation reaction proceeds, degree of polymerization, N, increases, which reduces mobility and miscibility of the growing polymers with 1-decanol due to the large molecular weight and increase of mixing energy; a low 6030
DOI: 10.1021/acs.langmuir.5b01129 Langmuir 2015, 31, 6027−6034
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Figure 4. (a−c) Schematic illustration and confocal microscope images of microcapsules dispersed in a binary mixture of red-fluorescent particles with diameter of 217 nm and FITC-dextran with molecular weight of 2 000 000 g/mol, where the membrane pores are made by 15 wt/wt % porogen of 1-decanol. The membrane is impermeable for the particles (b) and permeable for the dextran (c). (d−f) Schematic illustration, optical microscope and confocal microscope images of microcapsules dispersed in aqueous solution of rhodamine 6G, where the capsule membrane is made from photocurable resin without porogen. The membrane is impermeable for rhodamine 6G (f). (g) Time-dependence of normalized fluorescence intensity in the interior of microcapsules for FITC-tagged dextran with Mw = 20 000 g/mol (squares), Mw = 70 000 g/mol (circles), and Mw = 150 000 g/mol (triangles).
make porous microspheres from single-emulsion drops.32,33 To confirm the formation of regular pores, the microcapsules are dried and observed with scanning electron microscope (SEM). As water evaporates from the interior, the microcapsules are fully deflated while maintaining integrity of the membrane, as shown in Figure 2c,d. Such high structural stability is attributed to the monolithic membrane composed of a cross-linked network of GMA and ETPTA. High flexibility of the membrane is attributed to the thinness of the membrane; the membrane is 700 nm-thick, as shown in Figure 2e. The surface of the microcapsules exhibits consistent size and shape of pores, as shown in the inset of Figure 2e. The membrane cross-section shows that the pores interconnect the interior and exterior of the microcapsules as shown in Figure 2e, thereby potentially providing size-selective transport of materials through the pores in the membrane. Control of Porosity with Porogen Fraction. The porosity and pore size can be controlled by adjusting the fraction of porogen, 1-decanol, as shown in Figure 3. Without porogen in the middle phase, a dense membrane is formed as
Subsequent washing of the microcapsules removes 1-decanol from the polymerized matrix, which leaves behind pores in the membrane, as illustrated in Figure 2a. The porogen can be quickly removed by washing with methanol and subsequently with acetone and distilled water; methanol and acetone can be critical to delicate encapsulants in the core. Alternatively, the porogen of 1-decanol can be slowly but steadily removed by washing with water only. When the microcapsules are washed with distilled water every 30 min, the membrane becomes permeable in 5 h; water is totally compatible with any delicate encapsulants. During the washing step, the majority of indented capsules recover their spherical shape, as shown in Figure 2b. The formation of pores in the membrane might release the negative pressure in the interior of capsule, which is built by sudden expansion of impermeable shell, possibly leading to recovery of spherical shape. The microcapsules appear translucent due to weak light scattering caused by membrane pores that are filled with water; an oil-filled membrane is transparent due to low index contrast, as shown in Figure 1d. Such polymerization-induced phase separation has been used to 6031
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Figure 5. (a−c) Optical microscope and SEM images of monodisperse microcapsules whose membrane pores are made by 15 wt/wt % porogen of butyl acetate. (d,e) Schematic illustration and confocal microscope images of the microcapsules dispersed in a binary mixture of FITC-dextran with molecular weight of 500 000 g/mol and RITC-dextran with molecular weight of 10 000 g/mol. The membrane is impermeable for the FITC-dextran (e) and permeable for the RITC-dextran (f).
To estimate the permeability for the porous membrane made with 15 wt/wt % of 1-decanol, we employ FITC-tagged dextran with three different molecular weights of 20 000 g/mol, 70 000 g/mol, and 150 000 g/mol; hydrodynamic diameter of the molecules are 7, 12, and 17 nm, respectively. We directly disperse the microcapsules in 2.5 × 10−3 M aqueous solution of each dextran molecule and observe infusion of the molecule toward the interior of microcapsules, as shown in Figure S5. Fluorescence intensity in the interior, I(t), increases as the molecule diffuses through porous membrane and reaches the maximum, Imax, for sufficiently long time, as shown in Figure 4g. The permeability of each molecule is estimated with a diffusion equation:
shown in Figure 3a. As the weight fraction of 1-decanol is increased to 10%, 15%, and 20%, while retaining a constant weight ratio of GMA to ETPTA as 3:2, both porosity and pore size increases, as shown in Figure 3b−d; the average sizes of surface pores are 160, 205, and 295 nm respectively, as shown in Figure 3e, where we define the pore size as the maximum diameter of a circle that can fit into the pore. The coefficient of variation of the pore size is maintained as small as 19% for all fractions, indicating consistent size of pores throughout each membrane. Further increase of porogen fraction frequently results in rupture of the double-emulsion template or severe deformation during polymerization as shown in Figure S2 of the Supporting Information. Size-Selective Permeability. Although the pores can be visualized by SEM, it is difficult to estimate the cutoff value of permeation because the pores are not straight but randomly wiggled with varied width as shown in Figure 2e. To estimate the cutoff value and demonstrate selective permeability, we disperse the microcapsules, made with a middle phase containing 15 wt/wt % 1-decanol, into a binary aqueous mixture of FITC-tagged dextran (Mw = 2 000 000 g/mol) and red-fluorescent PS particles with 217 nm diameter for 1 day as schematically illustrated in Figure 4a; 1 day is sufficiently long for material diffusion along the submicron thick membrane if the membrane is permeable to the material. The microcapsules exclude the red-fluorescent particles (217 nm diameter) as shown in Figure 4b, while allowing the diffusion of the FITCdextran into the interior of the microcapsules as shown in Figure 4c; low magnification images are included in Figure S3 of the Supporting Information. This indicates that the cutoff value of permeation is larger than the hydrodynamic diameter of FITC-tagged dextran, approximately 60 nm, and smaller than 217 nm. By comparison, we confirm very low permeability of the membrane made from only GMA and ETPTA without porogen; the microcapsules dispersed in an aqueous solution of small red dye molecules of rhodamine 6G (Mw = 479.02 g/ mol) do not allow the diffusion of the dye molecules into their interior, as shown in Figure 4d−f and Supporting Information Figure S4, indicating the formation of dense membrane even without 1-nanometer-size pores.
3P I (t ) = 1 − e−( r )t Imax
(1)
where P is permeability, r is radius of the microcapsule and t is diffusion time.23 The permeability of FITC-dextran molecules with molecular weight of 20 000 g/mol, 70 000 g/mol, and 150 000 g/mol is measured as 1.432 μm/s, 0.4163 μm/s, and 0.1739 μm/s, respectively. The permeability of dextran with molecular weight of 70 000 g/mol and 150 000 g/mol is 3.44 and 8.23 times smaller than that with molecular weight of 20 000 g/mol, respectively, although their hydrodynamic diameters are only 1.7 and 2.4 times smaller; diffusivity is inversely proportional to molecule diameter for free diffusion in dilute solution. This is because diffusion is more suppressed for molecules whose diameter is closer to pore size. Control of Cutoff Value of Permeation. A higher affinity of porogen to the polymers leads to a low degree of phase separation. Therefore, we can produce much smaller pores by replacing 1-decanol with other liquids which have lower interaction parameters with the polymers made from GMA and ETPTA than 1-decanol. For example, butyl acetate, which has a higher affinity to the polymers, can be used instead of 1decanol to produce nanopores. Following the same procedures for drop generation, photopolymerization, and removal of porogen, we can produce microcapsules with a middle phase containing 15 wt/wt % butyl acetate, as shown in Figure 5a. However, the surface of the microcapsules does not show any 6032
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discernible pores in the SEM images, as shown in Figure 5b and 5c; we attribute this to the low degree of phase separation, which produces pores smaller than the resolution limit of the SEM. To estimate the pore size and cutoff value of permeation, we disperse the capsules into a binary aqueous mixture of FITC-dextran (Mw = 500 000 g/mol) and rhodamine B isothiocyanate (RITC)-dextran (Mw = 10 000 g/mol), as shown in Figure 5d. After 24 h of incubation, FITC-dextran is excluded from the microcapsules as shown in Figure 5e, while the RITC-dextran selectively diffuses into the interior of the microcapsules as shown in Figure 5f; low magnification images are included in Figure S6 of the Supporting Information. This indicates that the cutoff value of permeation is larger than hydrodynamic diameter of the RITC-dextran, approximately 4.4 nm, and smaller than hydrodynamic diameter of the FITCdextran, approximately 30 nm. When the microcapsules are dispersed in an aqueous solution of FITC-dextran with molecular weight of 20 000 g/mol, we observe slow diffusion of the dextran into the interior of the microcapsules as shown in Figure S7 of the Supporting Information; it takes approximately 2 days to get comparable concentration of dextran in the interior of the capsule and in the surrounding fluid. When we assume that the highest fluorescence intensity from the interior among all the microcapsules incubated for 2 days corresponds to 95% of the steady state value, the average permeability of the molecule is estimated as 0.155 nm/s using eq 1 from the intensity distribution. The coefficient of variation (CV) of the permeability is 43.8%. These small permeability and large deviation are attributed to comparable size of pores to molecule diameter, confirming that the pore size is only slightly larger than 6.6 nm.
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ASSOCIATED CONTENT
S Supporting Information *
Optical microscope images showing drop generation and confocal microscope images showing selective permeability of microcapsules. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/ acs.langmuir.5b01129.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Author Contributions
S.-H.K. and B.K. designed the research and B.K. and T.Y.J. carried out all experiments. S.-H.K. and Y.-K.O. supervised the research. All authors discussed and interpreted the results. B.K. and S.-H.K. prepared the manuscript. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by the Midcareer Researcher Program (2014R1A2A2A01005813) through the National Research Foundation (NRF) grant funded by the MSIP, the Industrial Strategic Technology Development Program (No. 10045068) of the Korea Evaluation Institute of Industrial Technology (KEIT) funded by MOTIE and the Research and Development Program of the Korea Institute of Energy Research (KIER; B42434-01).
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REFERENCES
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CONCLUSIONS We produced monodisperse microcapsules whose ultrathin membranes have consistently sized pores, thereby providing size-selective permeability. Capillary microfluidic devices are employed to prepare monodisperse double-emulsion droplets with ultrathin shells, which serve as a template for making microcapsules. Phase separation between polymerized monomers and inert oil occurs within the thin middle layer of the double-emulsion templates upon UV-induced polymerization. The separated oil can be removed to create pores in the membrane, which interconnect the interior and exterior of the microcapsules, rendering the microcapsules semipermeable. The pore size and cutoff value of permeation are determined by the degree of phase separation, which is controlled by adjusting the fraction of porogen in the middle phase or by tuning the affinity of the porogen to the polymers. The high structural stability and well-defined permeability of the microcapsules made by our microfluidic approach will provide new opportunities for a wide range of biomedical and chemical applications. For example, cells can be encapsulated in the semipermeable capsules which allow diffusion of small nutrients and stimuli, while protecting the cells from large antibodies and immune cells; this enables the secretion of therapeutic agents from functional cells when the capsules are transplanted.12,13 In addition, semipermeable capsules can isolate cells while partially allowing diffusion of small molecules for cell signaling, thereby providing a useful tool to study cell-to-cell interaction. Catalysts enclosed by semipermeable membranes can promote chemical reactions while minimizing contamination from external conditions. 6033
DOI: 10.1021/acs.langmuir.5b01129 Langmuir 2015, 31, 6027−6034
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DOI: 10.1021/acs.langmuir.5b01129 Langmuir 2015, 31, 6027−6034
