Si Hyung Jin

Controlled fabrication of multicompartmental polymeric microparticles by sequential micromolding via surface-tension-induced droplet formation.

Polymeric multicompartmental microparticles have significant potential in many applications due to the capability to hold various functions in discrete domains within a single particle. Despite recent progress in microfluidic techniques, simple and scalable fabrication methods for multicompartmental particles remain challenging. This study reports a simple sequential micromolding method to produce monodisperse multicompartmental particles with precisely controllable size, shape, and compartmentalization. Specifically, our fabrication procedure involves sequential formation of primary and secondary compartments in micromolds via surface-tension-induced droplet formation coupled with simple photopolymerization. Results show that monodisperse bicompartmental particles with precisely controllable size, shape, and chemistry can be readily fabricated without sophisticated control or equipment. This technique is then extended to produce multicompartmental particles with controllable number of compartments and their size ratios through simple design of mold geometry. Also, core-shell particles with controlled number of cores for primary compartments can be readily produced by simple tuning of wettability. Finally, we demonstrate that the as-prepared multicompartmental particles can exhibit controlled release of multiple payloads based on design of particle compositions. Combined, these results illustrate a simple, robust, and scalable fabrication of highly monodisperse and complex multicompartmental particles in a controlled manner based on sequential micromolding.

Microfluidic preparation of a highly active and stable catalyst by high performance of encapsulation of polyvinylpyrrolidone (PVP)-Pt nanoparticles in microcapsules.

The encapsulation of active metals in microcapsules would be highly advantageous in maintaining or improving the reaction performance of an array of widely used chemical reactions. However, conventional methods suffer from low uniformity, complicated fabrication steps, sintering, leaching, decline of catalytic activity, and/or poor reusability. Here, we report an efficient microfluidic approach to encapsulate Pt nanoparticle stabilized by polyvinylpyrrolidone (PVP) in photocurable double-emulsion droplets with semipermeable thin shells. The encapsulated catalysts are prepared by the in situ photopolymerization of a double emulsion. The rapid and exquisite microfluidics-based fabrication process successfully generates monodisperse microcapsules without loss of the PVP-Pt nanoparticles, which is the first demonstration of the microfluidic encapsulation of active metal with promising catalytic activity. Specifically, compared to quasi-homogeneous catalysis of PVP-Pt nanoparticles for 4-nitrophenol hydrogenation, the encapsulated PVP-Pt nanoparticles demonstrate excellent catalytic activity, a leaching-proof nature, and high reusability under the same reaction conditions. We envision that the approach described here may be an example of elegant catalyst design to efficiently overcome difficult problems in active-metal encapsulation and to dramatically enhance catalytic activity by taking advantage of the unique aspects of microfluidic methods.

Flow control in paper-based microfluidic device for automatic multistep assays: A focused minireview

Although lateral flow tests (LFTs) are easy-to-use diagnostics, they have fundamental limitations for sequential multistep assay that can be reduced to a single chemical reaction step. Paper-based microfluidic devices have attracted considerable attention for use in automatic multi-step assays because paper can be an excellent platform to control sequential fluid flow without external equipment. This review focuses on recent developments on how to control flow rate in paper-based microfluidic devices for automating sequential multi-step assays. The aim of this review is to discuss the limitations of LFTs and potential paper-based microfluidic devices for automated sequential multi-step assays in developing countries; and the existing fluidic control technologies for sequential multi-step assays. In addition, we present future challenges for commercialization of paper-based microfluidic devices to perform automatic multi-step assays.

Programmable Static Droplet Array for the Analysis of Cell–Cell Communication in a Confined Microenvironment

Direct cell-cell communication can occur through various chemical and mechanical signals. However, available cell culture systems lack single-cell resolution and are often limited by sensitivity and accuracy. In this study, we present an accurate, efficient and controllable microfluidic device that can be used for in situ monitoring of natural cell-cell contact and signaling processes in a confined microenvironment. This innovative static droplet array (SDA) enables highly efficient trapping, encapsulation, arraying, storage, and incubation of defined cell populations. For proof-of-principle experiments, we monitored the response of budding yeast to peptide mating pheromones, as it is one of the best understood examples of eukaryotic cell-cell communication. Specifically, we measured the yeast response to varying concentration of synthetic MATα-type mating factor, as well as varying the cell number ratio of MATα and MATa in a confined space. We found clear morphological and doubling-time changes during the mating reaction with a significantly higher accuracy than conventional methods. Further, phenotypic analysis of data generated with the microfluidic static droplet array allowed distinguishing the function of genes in yeast mutants defective for different aspects of pheromone signaling. Taken together, the microfluidic platform provides a valuable research tool to study cell-cell communication and signaling in a controlled microenvironment with the sensitivity and accuracy required for screening and long-term phenotypic analysis.

Optimization of microwell-based cell docking in microvalve integrated microfluidic device

This study presents a novel cell docking system based on microwells integratded with microvalves. Conventional cell docking device based on micro-well suffers from generation of dead volume and shear stress within micro-wells resulting in low efficiency of cell docking, limitation of nutrient, and low cell viability. Our approach to solve the problems adopts integration of microvalve controlled by pressure with microwells for provinding guided flow stream of cells and nutrients into microwell. We have optimized the efficiency of cell docking by varying several experimental parameters including flow rate, cell concentration, microvalve pressure, and size of microvalve. Under the optimized flow rate (1 µL/sec) and valve pressure (0.2 MPa), we obtain high efficiency of cell docking as 14.1 cells/microwell. In this study, we confirm that the perfusion culture of cells in microfluidic chip provides suitable environmental condition for cell culture at small scale and demonstrate the feasibility of universal cell culture platform.

Microfluidic dual loops reactor for conducting a multistep reaction

Precise control of each individual reaction that constitutes a multistep reaction must be performed to obtain the desired reaction product efficiently. In this work, we present a microfluidic dual loops reactor that enables multistep reaction by integrating two identical loop reactors. Specifically, reactants A and B are synthesized in the first loop reactor and transferred to the second loop reactor to synthesize with reactant C to form the final product. These individual reactions have nano-liter volumes and are carried out in a stepwise manner in each reactor without any cross-contamination issue. To precisely control the mixing efficiency in each loop reactor, we investigate the operating pressure and the operating frequency on the mixing valves for rotary mixing. This microfluidic dual loops reactor is integrated with several valves to realize the fully automated unit operation of a multistep reaction, such as metering the reactants, rotary mixing, transportation, and collecting the product. For proof of concept, CdSeZn nanoparticles are successfully synthesized in a microfluidic dual loops reactor through a fully automated multistep reaction. Taking all of these features together, this microfluidic dual loops reactor is a general microfluidic screening platform that can synthesize various materials through a multistep reaction.

Microfluidic preparation of monodisperse polymeric microspheres coated with silica nanoparticles

The synthesis of organic-inorganic hybrid particles with highly controlled particle sizes in the micrometer range is a major challenge in many areas of research. Conventional methods are limited for nanometer-scale fabrication because of the difficulty in controlling the size. In this study, we present a microfluidic method for the preparation of organic-inorganic hybrid microparticles with poly (1,10-decanediol dimethacrylate-co-trimethoxysillyl propyl methacrylate) (P (DDMA-co-TPM)) as the core and silica nanoparticles as the shell. In this approach, the droplet-based microfluidic method combined with in situ photopolymerization produces highly monodisperse organic microparticles of P (DDMA-co-TPM) in a simple manner, and the silica nanoparticles gradually grow on the surface of the microparticles prepared via hydrolysis and condensation of tetraethoxysilane (TEOS) in a basic ammonium hydroxide medium without additional surface treatment. This approach leads to a reduction in the number of processes and allows drastically improved size uniformity compared to conventional methods. The morphology, composition, and structure of the hybrid microparticles are analyzed by SEM, TEM, FT-IR, EDS, and XPS, respectively. The results indicate the inorganic shell of the hybrid particles consists of SiO2 nanoparticles of approximately 60 nm. Finally, we experimentally describe the formation mechanism of a silica-coating layer on the organic surface of polymeric core particles.

Nanoliter scale microloop reactor with rapid mixing ability for biochemical reaction

The mixing rate is a crucial factor in determining the reaction rate and product distribution in reactors for academic and industrial application. Especially, in pharmaceutical or dangerous chemistry, it is essential to create rapidly homogeneous mixture under the control of a small volume of precious sample. In this study, we propose a microloop reactor that is capable of rapid mixing for homogeneous reaction by utilizing programmable actuated microvalves (PAVs), which can generate the rotary flow rapid mixing in the reactor. The microloop reactor is composed of a stacked layered structure, which is prepared by a soft lithography method. The top layer (fluidic layer) has microchannels for supplying each reagent that is assembled with the bottom layer (control layer). The bottom layer has ultrathin polymer membrane, which can be an on-off valve to precisely control the nanoliter-scale volume of reagents in the reactor. To evaluate mixing performance, we use peroxidase reaction that produces fluorescent by-product (resorufin), thereby observing how fast they are mixed together. We quantify the uniformity of fluorescent intensity throughout the reaction loop, indicating that our proposed microloop reactor exhibits a homogeneous reaction. We envision the microreactor has potential to provide optimized microenvironments in which to perform dangerous chemistry, pharmaceuticals.

Spontaneous generation of emulsion droplets by autonomous fluid-pumping using the gas permeability of poly(dimethylsiloxane) (PDMS)

ABSTRACT Conventional droplet-based microfluidic systems require expensive, bulky external apparatuses, such as electric power supplies and pressure-driven pumps for fluid transportation. This study demonstrates an alternative way to produce emulsion droplets by autonomous fluid-handling based on the gas permeability of poly(dimethylsiloxane) (PDMS). Furthermore, basic concepts of fluid-handling are expanded to control the direction of the microfluid in the microfluidic device. The alternative pumping energy resulting from the high gas permeability of PDMS is used to generate water-in-oil (W/O) emulsions, which require no additional structures apart from microchannels. We can produce emulsion droplets by simple loading of the oil and aqueous solutions into the inlet reservoirs. During the operation of the microfluidic device, changes in droplet size, volumetric flow rate, and droplet generation frequency were quantitatively analyzed. As a result, we found that changes in the wetting properties of the microchannel greatly influence the volumetric flow rate and droplet generation frequency. This alternative microfluidic approach for preparing emulsion droplets in a simple and efficient manner is designed to improve the availability of emulsion droplets for point of care bioanalytical applications, in situ synthesis of materials, and on-site sample preparation tools. GRAPHICAL ABSTRACT