Dynamic Interfacial Printing for Monodisperse Droplets and Polymeric Microparticles

A dynamic interfacial printing technique (DIP) is developed for preparing monodisperse droplets and polymer particles with high degree of uniformity. The DIP system is cost effective and it can be set up in a few minutes. The printing pipeline endures almost all the organic solvents, offering great promise for exploiting functional droplets or particles with long-term service. Polymeric particles of micrometer size have attracted tremendous attention in the areas of controlled release,1, 2 biomedical imaging,3, 4 optoelectronics,5 reinforcement materials,6 and photonic crystals.7 In addition to exploiting particles with diverse shapes, great efforts have been devoted to improving the degree of particle uniformity and regulating particle composition.8, 9 The precise control over uniformity and composition of polymer particles has led to a remarkable increase of repeatability and reliability in their valid application.10, 11 Traditional emulsion ways provide a facile and large-scale platform for converting polymers into solid particles, while polymer particles as a result of solidification of emulsion droplets always take the form of polydispersity.12 The microfluidic technique appears to be the most powerful tool to produce monodisperse droplets with the size ranging from several to hundred micrometers, affording great promise for the generation of polymeric microparticles with high uniformity.13-21 However, serious deformation of elastomeric microchannels by organic solvent is always raised on account of the swelling issue.22-24 This intrinsic incompatibility restricts the use of many theta solvents for dissolving particular polymers. Microfluidic devices composed of silicon,25 glass,26-28 or perfluoropolyether29, 30 have come into being which exhibit effective solvent resistance. Yet their preparation routinely relies on time-consuming and sophisticated microfabrication processes. The innovation of inkjet printing, e.g., Jetlab Printer,31 provides a new platform for establishing droplets on demand, with droplet size closely constrained by the inner diameter of the nozzle. It is claimed that most solvents can be printed into uniform droplets by Jetlab Printer as its nozzle is made of glass. However, the printer is extremely expensive in comparison with microfluidic techniques and the inks should possess proper viscosity and surface tension though the printer affords great convenience to microengineering. Herein, we developed a dynamic interfacial printing (DIP) technique for preparing monodisperse droplets as well as polymeric microparticles. Different from the conventional inkjet printer with static nozzles, the DIP instrument has a dynamic nozzle periodically tapping an air–water interface. Similar to microfluidic devices, the droplets are formed due to interfacial shearing instead of piezoelectric pushing used in inkjet printing. DIP devices are free of photolithography and can be manually assembled within several minutes. It produces highly uniform polymeric microparticles with precise control over size in a wide range. In addition to cost effective preparation, the printing module made of Teflon and silica capillary tubes exhibits perfect compatibility with organic solvents and polymers. Figure 1a illustrates the components and assembly of a typical DIP system. Polymer solution is injected by a programmable syringe pump into a water pool through a silica capillary tube connected with a gastight syringe via a Teflon tube. A vibration system including an electric vibrator and a function generator provides the driving force for vibrating the silica capillary tube at air–water interface. In a typical DIP process, the silica capillary tube anchored on the vibrator, acting like a dynamic nozzle, periodically goes up and down across an air–water interface (Figure 1b; Movie S1, Supporting Information). Along with the interfacial vibration, an oil phase is pumped out of the nozzle from the injection system into a water phase, which is sheared into a uniform droplet each time the nozzle leaves the interface. Without special statement, sodium lauryl sulfate (SDS) serving as a surfactant is added in the water phase in order to stabilize the oil droplets. As shown in Figure 1c,d, a model solvent of carbon tetrachloride (CCl4) was printed into droplets with high degree of uniformity. At given flow rate and vibration frequency, the size of CCl4 droplets is almost retained at a constant value (average diameter ≈31.8 μm, at flow rate of 0.06 μL min–1 and vibration frequency of 50 Hz). Statistical analysis reveals that the polydispersity index (PDI) of droplet diameters is as low as 4.4%. The DIP printed droplets render the possibility to serve as templates for preparing various polymeric microparticles. A volatile solvent of chloroform loaded with polymethylmethacrylate (PMMA) was printed into monodisperse droplets followed with the evaporation of chloroform. As shown in Figure 1e, complete removal of chloroform yielded solid PMMA particles with a narrow size distribution (Figure 1f). To clarify the principle of droplet formation by DIP, the dynamic printing process was viewed and captured on a high-speed camera. As played in Movie S2 (Supporting Information) (recording frame rates, 2000 fps), the droplet outflows from the nozzle and grows bigger below the air–water interface. Each time the nozzle goes up above the interface, the droplet is sheared by the interface and escapes from the nozzle. The droplets settle down or float up in the water pool if the solvent density is higher (e.g., CCl4, see Movie S2, Supporting Information) or lower (e.g., n-octane, see Movie S4, Supporting Information) than the density of water. There are two key forces in determining the formation of oil droplets: (1) a strong enough capillary force that can hold the oil droplet moving together with the nozzle at high speed and acceleration below the interface; (2) a shearing force that can cut off the pendant oil droplet from the nozzle near the interface. Based on the analysis of movies captured on the high speed camera, parameters relevant to the motion of nozzle can be figured out. Two critical parameters of velocity and acceleration, which decide the Stokes force and the total force respectively, change periodically as function of nozzle position or vibration time in a typical harmonic motion driven by an AC (Figure S1, Supporting Information). Accordingly, as discussed in detail in Note S2 (Supporting Information), the total force and Stokes drag force change dynamically in the whole vibration process. Gravity as well as buoyancy forces are also variable at different positions due to the change of droplet volume. Regardless of the change of injection pressure force, the dynamic capillary force needed to balance the motion of droplet with nozzle from the lowest position to equilibrium location (stage II as presented in Note S2, Supporting Information) are estimated in Figure S2 (Supporting Information). A capillary force of 4.93 × 10−8 N appears at the equilibrium state where the velocity reaches its maximum. As explained in Note S2 (Supporting Information), this value is regarded as the maximum capillary force in the whole vibration process. Remarkably, it is smaller than the theoretical maximum capillary force about 3.44 × 10−7 N provided by the nozzle, indicating that the capillary force is strong enough to hold the oil droplet moving at high speed and high acceleration below the air–water interface. In terms of high compatibility, the DIP printer composed of only silica and Teflon is able to endure almost all the organic solvents and surfactants in water phase. Several solvents that are immiscible with water, such as toluene, n-octane, tetrachloromethane, chloroform, and chlorobenzene have been attempted. These solvents can all be printed into monodisperse droplets with precise control over the size. The droplets made of them at the same conditions can not be distinguished except the different density (Figure S9, Supporting Information). In addition to SDS, the use of another common surfactant of polyvinyl alcohol can also lead to monodisperse and stable oil droplets. Yet the droplets printed into aqueous solution having cetyl trimethyl ammonium bromide (CTAB) are not uniform (Figure S10c, Supporting Information). This exceptional printing is attributed to the adhesion of CTAB on the outer surface of silica nozzle due to the electrostatic interaction between cation of CTAB and hydroxyl moieties on silica surface (Figure S11, Supporting Information). As a consequence, the oil droplets are able to wet the outer surface of silica nozzle which causes an irregular interfacial shearing. The adhesion of CTAB could be hampered by assembling a layer of 3-aminopro­pyltrimethoxysilane with the ability of repulsing CTAB on the silica nozzle. Again, oil phase becomes nonwetting to the silica nozzle and can be sheared into monodisperse droplets (Figure S10d, Supporting Information). Monodisperse droplets made of diverse solvents by the DIP technique afford a great platform for preparing polymeric microparticles with a high degree of uniformity. In principle, polymers dissolved in oil droplets can be condensed into solid particles upon the removal of solvents. Particle size relies on the polymer concentration as well as the droplet size. Taking polystyrene (PS) as an example, its chloroform solution can be readily printed into droplets and turned into microparticles upon the evaporation of chloroform. At the given flow rate and vibration frequency, the droplet size was not affected by polymer concentration, while lower concentration led to smaller polystyrene particles (Figure 4a–c). The particle volume is theoretically proportional to the polymer concentration, which is verified by multiple practices at different concentrations (Figure 4d). It is worth noting that many other polymers can be printed into solid particles by the DIP technique. As exemplified in Figure S12 (Supporting Information), biodegradable polymers like polylactic acid and polycarbonate, and block copolymers such as polystyrene-polymethyl methacrylate and polymethyl methacrylate-polyacrylonitrile have been successfully converted into microparticles. To realize its full potential, DIP was extended to prepare polymeric microparticles with complicated morphologies. Three examples were presented, including elongated particles, particles with patchy surfaces, and porous particles (Figure 5). They have always been considered as star building blocks for colloid assembly and functional materials.32-36 Elongated particles were attained by stretching polycaprolactone (PCL) particles that have been prepared already based on DIP (Figure 5a). Notably, DIP promised high degree of uniformity not only to spherical particles but also elongated particles. Patchy particles were formed based on the phase separation within a blend of PS and PMMA. Droplets dissolving two free polymers of PS and PMMA were allowed to be printed and solidified. Macrophase separation between PS and PMMA drives one polymer to migrate onto the particle surface, although we have not yet recognized which polymer is pushed out. Porous particles were synthesized based on in situ polymerization within droplets. A photocurable monomer having three active groups (Triacrylate) was loaded in droplets which can be cross-linked into a gel together with solvents under UV irradiation.37 Porous morphology is a result of the complete removal of solvents. These examples are opening three possibilities: (1) DIP printed particles can be re-shaped. Shape-specific particles with high uniformity may facilitate the accurate understanding of shape effect in biological application since the particle shape has great effect to cellular interaction.38 (2) Multiple components can be loaded in particles. Based on phase separation, uniform microparticles with other topologies, including dumbbell, core-shell, onion, are anticipated. (3) DIP droplets can serve as microreactors. In addition to photopolymerization, other chemical or biological reactions may be involved in the droplets. For example, sequencing or amplification of nucleic acid in the size-specific microdroplets has great potential for polymerase chain reaction (PCR) application. In summary, we described a paradigm, simple, and low-cost DIP technique for preparing monodisperse droplets and uniform polymeric microparticles. Generation of droplets happens at an air–water interface based on an interfacial shearing. The method is like a combination of microfluidic flowing with periodical printing, affording great convenience to turn solutions into droplets. We provided a comparison of the DIP technique with other methods for generating liquid droplets (Table 1). Overall, DIP technique is most cost effective and generally applicable. The DIP printer could be rapidly built up with the use of readily available components. Unlike the most common polydimethylsiloxane-based microfluidic devices, the pipeline of DIP system endures almost all the organic solvents. In addition to preparing oil-in-water type of droplets, DIP technique can be principally extended to other combinations containing two or more immiscible phases, e.g., printing water into oil, air into water, water into water, or oil into oil. Convenient insights at various interfaces or within droplets are promised at macroscopic level. It is also believed that enclosing many other functional excipients in polymeric particles may broaden the range of materials with spatiotemporal functions. Great efforts have been devoted to integrating multiple nozzles in the DIP system for improving the throughput of droplets. Moreover, the development of high-level printers able to integrate multiple components in one droplet is undergoing. It is anticipated that some challengeable studies will be possibly launched based on the DIP technique. This work was financially supported by the National Natural Science Foundation of China (Grants Nos. 51373197, 21422407, 21205134, 31470221), the Program for New Century Excellent Talents in University (NCET-12-0530), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB15040102). As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. 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