Je-Kyun Park

Korea Advanced Institute of Science and Technology, Daiden, Daejeon, South Korea

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Publications (141)510.44 Total impact

  • Jaejung Son · Chae Yun Bae · Je-Kyun Park
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    ABSTRACT: Hydrogels can be patterned at the micro-scale using microfluidic or micropatterning technologies to provide an in vivo-like three-dimensional (3D) tissue geometry. The resulting 3D hydrogel-based cellular constructs have been introduced as an alternative to animal experiments for advanced biological studies, pharmacological assays and organ transplant applications. Although hydrogel-based particles and fibers can be easily fabricated, it is difficult to manipulate them for tissue reconstruction. In this video, we describe a fabrication method for micropatterned alginate hydrogel sheets, together with their assembly to form a macro-scale 3D cell culture system with a controlled cellular microenvironment. Using a mist form of the calcium gelling agent, thin hydrogel sheets are easily generated with a thickness in the range of 100 - 200 µm, and with precise micropatterns. Cells can then be cultured with the geometric guidance of the hydrogel sheets in freestanding conditions. Furthermore, the hydrogel sheets can be readily manipulated using a micropipette with an end-cut tip, and can be assembled into multi-layered structures by stacking them using a patterned polydimethylsiloxane (PDMS) frame. These modular hydrogel sheets, which can be fabricated using a facile process, have potential applications of in vitro drug assays and biological studies, including functional studies of micro- and macrostructure and tissue reconstruction.
    No preview · Article · Jan 2016 · Journal of Visualized Experiments
  • Jaejung Son · Chae Yun Bae · Je-Kyun Park
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    ABSTRACT: Hydrogel-based bottom-up tissue engineering depends on assembly of cell-laden modules for complex three-dimensional tissue reconstruction. Though sheet-like hydrogel modules enable rapid and controllable assembly, they have limitations in generating spatial microenvironments and mass transport. Here, we describe a simple method for forming large-scale cell-hydrogel assemblies via stacking cell-embedded mesh-like hydrogel sheets to create complex macroscale cellular scaffolds. Freestanding stacked hydrogel sheets were fabricated for long-term cell culturing applications using a facile stacking process where the micropatterned hydrogel sheets (8.0 mm × 8.7 mm) were aligned using a polydimethylsiloxane drainage well. The stacked hydrogel sheets were precisely aligned so that the openings could facilitate mass transport through the stacked sheets. Despite the relatively large height of the stacked structure (400-00 μm), which is larger than the diffusion limit thickness of 150-200 μm, the freestanding cell-ydrogel assemblies maintained cell viability and exhibited enhanced cellular function compared with single hydrogel sheets. Furthermore, a three-dimensional co-culture system was constructed simply by stacking different cell-containing hydrogel sheets. These results show that stacked hydrogel sheets have significant potential as a macroscale cell-culture and assay platform with complex microenvironments for biologically relevant in vitro tissue-level drug assays and physiological studies.
    No preview · Article · Dec 2015 · Biotechnology Journal
  • Jae Hoon Oh · Moon Kyoo Park · Seong Wook Kim · Je-Kyun Park
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    ABSTRACT: Allergy testing is important for evidence-based care and treatment. In this paper, we report a new clinical laboratory instrument, AdvanSure AlloStation Smart, which is used for a multiple allergen-specific immunoglobulin (IgE) assay. For efficient automation of immunoblot procedures, a novel tilting carousel technology was incorporated. The analyzer showed 100.5–101.7% of pipetting accuracy, no sample carryover, and 0.2–3.2% coefficient of variation of optical precision. Assay performance on the system was comparable with that of a single allergen test, ImmunoCAP for 23 allergens. The slope and the intercept of this comparison were 0.994 and 0.070, respectively. The Pearson correlation coefficient between two methods was r = 0.836. The coefficient of variation of intra-assay precision ranged from 3.2% to 11.1% and that of inter-assay precision varied from 4.0% to 17.6%. The AdvanSure AlloStation Smart provides a simple and reliable multiple assay platform to monitor allergen-specific IgE profiles.
    No preview · Article · Sep 2015 · Analytical methods
  • Dongsik Han · Je-Kyun Park

    No preview · Article · Sep 2015 · Biosensors & Bioelectronics
  • Seyong Kwon · Chang Hyun Cho · Eun Sook Lee · Je-Kyun Park
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    ABSTRACT: We report an automated multiple biomarker measurement method for tissue from cancer patients using quantum dot (QD)-based protein detection combined with reference-based protein quantification and autofluorescence (AF) removal. For multiplexed detection of biomarkers in tissue samples, visualization of QDs on cytokeratin was performed to create a multi-channel microfluidic device on sites with dense populations of tumor cells. Three major breast cancer biomarkers (i.e., estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) were labeled using QDs successively on cancer cells in tissue sections. For the automated measurement of biomarkers, a cytokeratin-based biomarker normalization method was used to measure the averaged expression of proteins. A novel AF-removal algorithm was developed, which normalizes the reference AF spectra reconstructed from unknown AF spectra based on random sampling. For accurate quantification of QDs, we automatically and accurately removed the AF signal from 344 spots of QD-labeled tissue samples using 240 reference AF spectra. Using analytical data with 10 tissue samples from breast cancer patients, the measured biomarker intensities were in good agreement with the results of conventional analyses.
    No preview · Article · Mar 2015 · Analytical Chemistry
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    Do-Hyun Lee · Chae Yun Bae · Seyong Kwon · Je-Kyun Park
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    ABSTRACT: Cell-containing hydrogel modules, as cell–hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions, facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell–matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond current 2D cell-culture systems.
    Full-text · Article · Mar 2015 · Lab on a Chip
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    Joong Ho Shin · Juhwan Park · Je-Kyun Park · Seung-Hoon Kim
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    ABSTRACT: This paper reports a method to control the fluid flow in paper-based microfluidic devices simply by pressing over the channel surface of paper, thereby decreasing the pore size and permeability of a non-woven polypropylene sheet. As a result, fluid resistance is increased in the pressed region and causes flow rate to decrease. We characterize the decrease of flow rate with respect to different amounts of pressure applied, and up to 740% decrease in flow velocity was achieved. In addition, we demonstrate flow rate control in a Y-shaped merging paper and sequential delivery of multiple color dyes in a three-branched paper. Furthermore, sequential delivery of multiple fluid samples is performed to demonstrate its application in multi-step colorimetric immunoassay, which shows a 4.3-fold signal increase via enhancement step.
    Full-text · Article · Oct 2014 · Biomicrofluidics
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    Joong Ho · Myung Gwon Lee · Sungyoung Choi · Je-Kyun Park
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    ABSTRACT: This paper demonstrates an inertia-activated cell sorting method to separate cells based on their surface protein expression by using inertial microfluidics. Target cells are immune-specifically reacted with antibody-coated microbeads and then separated from nontarget cells. As a proof of concept, separation of MCF-7 breast cancer cells from U937 lymphoma cells was achieved with 97.6% target cell recovery rate, 95% nontarget cell rejection ratio, 73.8% purity, and an enrichment ratio of 93 at a total flow rate of 8.75 mL/h without using any external forces.
    Full-text · Article · Aug 2014 · RSC Advances
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    Jung Kim · Seyong Kwon · Je-Kyun Park · Inkyu Park
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    ABSTRACT: In this paper, we report an efficient and high-performance immunoassay platform by combining high-density vertical ZnO nanowire array with photostable quantum dot (QD) labeling. The ZnO nanowire array provides a large surface area for the immobilization of biomolecules, which makes it an efficient substrate for the immunoreaction of biomolecules. When a sandwich immunoassay with QD label was conducted on various substrates, the ZnO nanowire substrate showed stronger fluorescence signal than ZnO thin film and bare glass substrates by 3.8 and 8.5 times, respectively. We found that the fluorescence resonance energy transfer (FRET) from QD to ZnO nanowire could be suppressed by extending their distance with multilayer biotin–streptavidin complex. In addition, we demonstrated the QD-based immunoassay of carcinoembryonic antigen (CEA) on a ZnO nanowire substrate, showing an excellent immunoassay performance with a very low detection limit (0.001 ng/mL) and a large detection range up to 100 ng/mL.
    Full-text · Article · May 2014 · Biosensors & Bioelectronics
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    Chae Yun Bae · Mun-Kyeong Min · Hail Kim · Je-Kyun Park
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    ABSTRACT: A microstructure-based hydrogel was employed to study the relationship between spatial specificity and cellular behavior, including cell fate, proliferation, morphology, and insulin secretion in pancreatic β-cells. To effectively form homogeneous cell clusters in vitro, we made cell-containing hydrogel membrane constructs with an adapted grid structure based on a hexagonal micropattern. Homogeneous cell clusters (average diameter: 83.6 ± 14.2 μm) of pancreatic insulinoma (MIN6) cells were spontaneously generated in the floating hydrogel membrane constructs, including a hexagonal grid structure (size of cavity: 100 μm, interval between cavities: 30 μm). Interestingly, 3D clustering of MIN6 cells mimicking the structure of pancreatic islets was coalesced into a merged aggregate attaching to each hexagonal cavity of the hydrogel grid structure. The fate and insulin secretion of homogeneous cell clusters in the hydrogel grid structure were also assessed. The results of these designable hydrogel-cell membrane constructs suggest that facultative in vitro β-cell proliferation and maintenance can be applied to biofunctional assessments.
    Full-text · Article · Mar 2014 · Lab on a Chip
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    ABSTRACT: Conventional molecular profiling methods using immunochemical assays have limits in terms of multiplexity and the quantification of biomarkers in investigation of cancer cells. In this paper, we demonstrate a quantum dot (QD)-based microfluidic multiple biomarker quantification (QD-MMBQ) method that enables labeling of more than eight proteins immunochemically on cell blocks within 1 h, in a quantitative manner. An internal reference, β-actin, was used as a loading control to compensate for differences in not only the cell number but also in staining quality among specimens. Furthermore, the microfluidic blocking method exhibited less nonspecific binding of QDs than the conventional static blocking method.
    No preview · Article · Mar 2014 · Integrative Biology
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    ABSTRACT: Loss of contractility and acquisition of an epithelial phenotype of vascular smooth muscle cells (VSMCs) are key events in proliferative vascular pathologies such as atherosclerosis and post-angioplastic restenosis. There is no proper cell culture system allowing differentiation of VSMCs so that it is difficult to delineate the molecular mechanism responsible for proliferative vasculopathy. We investigated whether a micropatterned substrate could restore the contractile phenotype of VSMCs in vitro. To induce and maintain the differentiated VSMC phenotype in vitro, we introduced a micropatterned groove substrate to modulate the morphology and function of VSMCs. Later than 7(th) passage of VSMCs showed typical synthetic phenotype characterized by epithelial morphology, increased proliferation rates and corresponding gene expression profiles; while short-term culture of these cells on a micropatterned groove induced a change to an intermediate phenotype characterized by low proliferation rates, increased migration, a spindle-like morphology associated with cytoskeletal rearrangement and expression of muscle-specific genes. Microarray analysis showed preferential expression of contractile and smooth muscle cell-specific genes in cells cultured on the micropatterned groove. Culture on a patterned groove may provide a valuable model for the study the role of VSMCs in normal vascular physiology and a variety of proliferative vascular diseases.
    Full-text · Article · Feb 2014 · PLoS ONE
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    ABSTRACT: This paper describes enhanced blood plasma separation by modulating the inertial lift force for separation in a contraction–expansion array (CEA) microchannel. By changing a contraction channel length, we observed the force modulation effects for size-based particle separation. In the CEA device, there are two force components that act in opposite direction to separate particles by size. By lengthening the contraction region in the CEA microchannel, we can easily control the lateral migration of desired particles by modulating a single force component (inertial lift force) without affecting the other (Dean drag force). From the experimental results, the inertial force ratio was calculated for prediction of force superiority between inertial lift force and Dean drag force, and applied to determine design parameters of the CEA microdevice for blood plasma separation. Using the force modulation in the microchannel, we successfully demonstrated enhancement of inertial blood plasma separation from human whole blood with a substantially high blood cell rejection ratio and a separation yield of 92.6% and 69.5%, respectively, with a throughput of 5.4 × 1011 cells/min.
    Full-text · Article · Jan 2014 · Sensors and Actuators B Chemical
  • Seong-Won Nam · So Hyun Kim · Je-Kyun Park · Sungsu Park
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    ABSTRACT: Dielectrophoresis (DEP) is an effective method to trap, manipulate and separate various dielectric particles. To generate a DEP force, a spatially nonuniform electrical field has been generated by an array of electrodes, while electrodeless DEP has been accomplished by placing an insulating material between two electrodes. Here, we describe a new DEP method for generating a nonuniform electrical field using a slanted microchannel. The electric field gradient is induced due to a slope in the channel and can be used to move and separate particles. Based on the gradual electric field induced by three dimensional structure of the microchannel, our method enables particles of different sizes to be separated solely by DEP force without flow. The slanted microchannel was easily fabricated by a replica molding technique using a commercial UV-cured photopolymer (NOA 63) and bonded as an insulating layer between two indium-tin-oxide films. By applying the electrical field, polystyrene beads of different sizes (6-45 microm in diameter) were trapped and separated depending on the applied electric strength and frequency. Using this method, the opportunistic pathogen Pseudomonas aeruginosa attached to antibody-conjugated microbeads was successfully separated from Escherichia coli in a slanted microchannel.
    No preview · Article · Dec 2013 · Journal of Nanoscience and Nanotechnology
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    Do-Hyun Lee · Je-Kyun Park
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    ABSTRACT: Microparticle adsorption on microchannel walls occurs frequently due to nonspecific interactions, decreasing operational performance in pressure-driven microfluidic systems. However, it is essential for delicate manipulation of microparticles or cells to maintain smooth fluid traffic. Here, we report a novel microparticle injection technique, which prevents particle loss, assisted by sample injection along the direction of fluid flow. Sample fluids, including microparticles, mammalian (U937) and green algae (Chlorella vulgaris) cells, were injected directly via a through-hole drilled in the lateral direction, resulting in a significant reduction in microparticle attachment. For digital microfluidic application, the proposed regime achieved a twofold enhancement of single-cell encapsulation compared to the conventional encapsulation rate, based on a Poisson distribution, by reducing the number of empty droplets. This novel interconnection method can be straightforwardly integrated as a microparticle or cell injection component in integrated microfluidic systems.
    Full-text · Article · Dec 2013 · Electrophoresis
  • Chae Yun Bae · Mun-kyeong Min · Hail Kim · Je-Kyun Park
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    ABSTRACT: This paper demonstrates chemical response of MIN6 pseudo-islets using geometric controlled hydrogel constructs including hexagon-based mesh pattern. The MIN6-laden hydrogels with regular and irregular meshed geometric micropattern were simply fabricated, free-standing cultured and morphologically analyzed to examine the effect of the microscale hydrogel patterns on pancreatic cellular growth within hydrogel constructs. We also investigate MIN6 cellular viability in this hydrogel culture platform to a serotonin antagonist, SB204741, which has been associated with reduction in β-cell mass. On the basis of cellular response using size-controlled pseudo-islets, these artificial 3D cell clusters can be applied to a facultative in vitro -cell proliferation and maintenance for drug assay. Copyright © (2013) by the Chemical and Biological Microsystems Society All rights reserved. All rights reserved.
    No preview · Conference Paper · Oct 2013
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    Do-Hyun Lee · Chae Yun Bae · Jong-In Han · Je-Kyun Park
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    ABSTRACT: Microalgae, a group of microorganisms that grow using sunlight as the sole energy source and carbon dioxide as an only carbon source, have been considered as a feedstock of choice for the production of biofuels such as biodiesel. To explore the economic feasibility of such application, however, many technical hurdles must first be overcome; the selection and/or screening of competent species are some of the most important and yet challenging tasks. To greatly accelerate this rather slow and laborious step, we developed a droplet-based microfluidic system that uses alginate hydrogel microcapsules with a mean diameter of 26 μm, each of which is able to encapsulate a single microalgal cell. This novel device was successfully demonstrated using three microalgae species, namely, Chlorella vulgaris , Chlamydomonas sp., and Botryococcus braunii . In situ analysis of the lipid content of individual microalgal cells by nondestructive fluorescence staining using BODIPY (4,4-difluoro-1,3,5,7,-tetramethyl-4-bora-3a,4a-diaza-s-indacene) was possible. In all cases, we confirmed that the lipid content of microalgal species in alginate hydrogel microcapsules was comparable to that of free-living cells. Stochastic heterogeneity in the lipid content was verified under a highly viable physiological condition, implying that other analyses were possible after the determination of lipid content. Furthermore, the designed microwell arrays enabled us to distinguish the BODIPY fluorescence response of a single live alga within the microcapsules.
    Full-text · Article · Sep 2013 · Analytical Chemistry
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    ABSTRACT: Towards potential applications in the field of nanomedicine, a new high-throughput synthesis method of lipid vesicles with tunable size as well as enhanced monodispersity is demonstrated using a semicircular contraction-expansion array (CEA) microchannel. Lipid vesicles are generated in the CEA microchannel by injecting lipids in isopropyl alcohol as a sample flow and phosphate buffered saline as a buffer flow, leading to spontaneous formation of lipid vesicles. In the CEA microchannel, Dean vortices cause three-dimensional (3D) lamination by continuously splitting and redirecting fluid streams, resulting in enhancement of fluid mixing. When considered only 3D laminating effect, it showed the best mixing efficiency in the range of flow rates of 12-15 mL/h. However, shear force effect also gives a strong influence on the formation of lipid vesicles, leading to the smallest size and uniform size distribution of lipid vesicles at a total flow rate of 18 mL/h. Consequently, from the interplay between high shear stress and 3D laminating effect, the lipid vesicles were generated with monodispersity and high throughput. The formation of lipid vesicles can be controlled with a total flow rate and a flow rate ratio between the sample and buffer fluids. The throughput of the lipid generation in the CEA microchannel was 10 times higher than previous works. In addition, the generated lipid vesicle populations were confirmed using a cryogenic transmission electron microscopy (cryo-TEM) technique.
    No preview · Article · Sep 2013 · BioChip journal
  • Joonwoo Jeong · Eujin Um · Je-Kyun Park · Mahn Won Kim
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    ABSTRACT: We present a simple method with the aid of a microfluidic droplet-generation technique to fabricate magnetic Janus particles by utilizing a solvent evaporation-induced phase separation and preferential partitioning of magnetic nanoparticles in the polymer blends. Non-aqueous emulsion droplets of the polymer blends and nanoparticles solution are produced to become Janus particles after the evaporation of the solvent. The stabilizing polymer of the nanoparticles, which is compatible only with one of the polymer blends to be phase-separated, plays a key role in the anisotropic positioning of the nanoparticles in the Janus particles. Using this phase separation-based method and microfluidics, excellent control over the size, size distribution, and morphology of the particles is achieved. Especially, we could control the morphology of the Janus particles easily by varying the volume ratio of the polymers. However, with an analysis of the shapes of resulting Janus particles, we found that non-equilibrium aspects of the evaporation-induced phase separation play a major role in determining the particle morphology. We expect that the versatility of this method in the choice of polymer blends and functional nanoparticles will enable the fabrication of colloids with various functionality and desired morphology.
    No preview · Article · Jun 2013 · RSC Advances
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    ABSTRACT: We report a contraction-expansion array (CEA) microchannel device that performs label-free high throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation using non-diluted whole blood sample (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9% and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by two-step filtration process with two devices connected in series.
    Full-text · Article · Jun 2013 · Analytical Chemistry

Publication Stats

3k Citations
510.44 Total Impact Points

Institutions

  • 2004-2015
    • Korea Advanced Institute of Science and Technology
      • • Department of Bio and Brain Engineering
      • • Department of Biological Sciences
      Daiden, Daejeon, South Korea
  • 2007
    • LG Electronics
      Sŏul, Seoul, South Korea
  • 2006
    • Kyung Hee University
      Sŏul, Seoul, South Korea