• Journal of Biosystems Engineering
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• v.39 no.3
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• pp.244-252
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• 2014

Purpose: The development of an efficient in vitro cell culture device to process various cells would represent a major milestone in biological science and engineering. However, the current conventional macro-scale in vitro cell culture platforms are limited in their capacity for detailed analysis and determination of cellular behavior in complex environments. This paper describes a microfluidic-based culture device that allows accurate control of parameters of physical cues such as pressure. Methods: A microfluidic device, as a model microbioreactor, was designed and fabricated to culture Saccharomyces cerevisiae and Chlamydomonas reinhardtii under various conditions of physical pressure stimulus. This device was compatible with live-cell imaging and allowed quantitative analysis of physical cue-induced behavior in yeast and microalgae. Results: A simple microfluidic-based in vitro cell culture device containing a cell culture channel and an air channel was developed to investigate physical pressure stress-induced behavior in yeasts and microalgae. The shapes of Saccharomyces cerevisiae and Chlamydomonas reinhardtii could be controlled under compressive stress. The lipid production by Chlamydomonas reinhardtii was significantly enhanced by compressive stress in the microfluidic device when compared to cells cultured without compressive stress. Conclusions: This microfluidic-based in vitro cell culture device can be used as a tool for quantitative analysis of cellular behavior under complex physical and chemical conditions.

• Journal of Biosystems Engineering
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• v.41 no.1
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• pp.60-65
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• 2016

Purpose: The necessity for precise manipulation of bioparticles has greatly increased in the fields of bioscience, biomedical, and environmental monitoring. Dielectrophoresis (DEP) is considered to be an ideal technique to manipulate bioparticles. The objective of this study is to develop a DEP microfluidic device that can trap fluorescent beads, which mimic bioparticles, at the low voltage and frequency of the sinusoidal signal supplied to the microfluidic device. Methods: A DEP microfluidic device, which is composed of polydimethylsiloxane (PDMS) channels and interdigitated electrode networks, is fabricated to trap fluorescent beads. The geometry of the interdigitated electrodes is determined through computational simulation. To determine the optimum voltage and frequency of the sinusoidal signal supplied to the device, the experiments of trapping beads are conducted at various combinations of voltage and frequency. The performance of the DEP microfluidic device is evaluated by investigating the correlation between fluorescent intensities and bead concentrations. Results: The optimum ratio of the widths between the negative and positive electrodes was 1:4 ($20:80{\mu}m$) at a gap of $20{\mu}m$ between the two electrodes. The DEP electrode networks were fabricated based on this geometry and used for the bead trapping experiments. The optimum voltage and frequency of the supplied signal for trapping fluorescent beads were 15 V and 5 kHz, respectively. The fluorescent intensity of the trapped beads increased linearly as the bead concentration increased. The coefficient of determination ($R^2$) between the fluorescent intensity and the bead concentration was 0.989. Conclusions: It is concluded that the microfluidic device developed in this study is promising for trapping bioparticles, such as a cell or virus, if they are conjugated to beads, and their concentration is quantified.

• Bulletin of the Korean Chemical Society
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• v.27 no.4
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• pp.479-483
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• 2006

We developed a microfluidic immunoassay platform for the detection of various analytes such as bacterial pathogen by packing antibody-immobilized glass beads in spatially-isolated microchambers on a microfluidic device. Primary amines of antibody were covalently conjugated to carboxyl-terminated glass beads previously treated with aminosilane followed by glutaraldehyde. Through this covalent binding, up to 905 $\mu$g immunoglobulin G (IgG) per gram of glass beads was immobilized. For application, glass beads attaching antibody specific to Escherichia coli O157:H7, a foodborne pathogen, were packed into a microfluidic device and used for the detection of the serotype. This prototype immunoassay device can be used for the simultaneous detection of multiple analytes by sequentially packing different-sized glass beads attaching different antibody in discrete microchambers on a single microfluidic device.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.17 no.2
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• pp.447-452
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• 2013

Microfluidic devices can offer precise control for a verity of tasks involving biological specimen. In this paper, we propose an integrated system consisting of a microfluidic device along with a digital holographic microscope and present three-dimensional (3D) sensing and segmentation of biological microorganisms. When the individual microorganisms are inputted into the microfluidic channel, the holographic microscope records their holograms. The holograms are computationally reconstructed in 3D using Fresnel transform and the reconstructed phase images are used to search the position of microorganisms. Optical experiments are carried out and experimental results are presented to illustrate the usefulness of the proposed system.

• Journal of the Korean Society of Visualization
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• v.16 no.1
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• pp.15-20
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• 2018

For the measurement of biophysical properties related with cardiovascular diseases (CVD), various microfluidic devices were proposed. However, many devices were monitored by optical equipment. Ultrasound measurement to quantify the biophysical properties can provide new insights to understand the cardiovascular diseases. This study aims to check feasibility of microfluidic device for ultrasound image analysis based on 3D printer. To facilitate acoustic transmission, agarose solution is poured around 3D mold connected with holes of the acrylic box. By applying speckle image velocimetry(SIV) technique, flow information in the bifurcated channel was estimated. Considering that ultrasound signal amplitude is determined by red blood cell (RBC) aggregation, RBC aggregation in the bifurcated channel can be estimated through the analysis of ultrasound signal. As examples of microfluidic device which mimic the CVD model, velocity fields in microfluidic devices with stenosis and aneurysm were introduced.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.380-388
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• 2018

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro, we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

• BioChip Journal
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• v.12 no.4
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• pp.294-303
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• 2018

Shear stress occurs in flowing liquids, especially at the interface of a flowing liquid and a stationary solid phase. Thus, it occurs inside the artery system of the human body, where it is responsible for a number of biological functions. The shear stress level generally remains less than $70dyne/cm^2$ in the whole circulatory system, but in the stenotic arteries, which are constricted by 95%, a shear stress greater than $1,000dyne/cm^2$ can be reached. Methods of researching the effects of shear stress on cells are of large interest to understand these processes. Here, we show the development of a microfluidic device for generating shear stress gradients. The performance of the shear stress gradient generator was theoretically simulated prior to experiments. Through simple manipulations of the liquid flow, the shape and magnitude of the shear stress gradients can be manipulated. Our microfluidic device consisted of five portions divided by arrays of micropillars. The generated shear stress gradient has five distinct levels at 8.38, 6.55, 4.42, 2.97, and $2.24dyne/cm^2$. Thereafter, an application of the microfluidic device was demonstrated testing the effect of shear stress on human umbilical vein endothelial cells.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2012.05a
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• pp.515-516
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• 2012

• Korean Chemical Engineering Research
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• v.52 no.2
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• pp.141-153
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• 2014

Droplet based microfluidic systems have been developed for the application of biological and chemical research field. A picoliter droplet in microfluidic device provides a compartmentalized and well-defined reactor in miniaturized system. The microfluidic system with small droplets can reduce reagent cost and enhance efficiency through automated high-throughput screening system. In this review, we summarize the functionality of droplet based microfluidic system including droplet generation, precise droplet control, and various applications. In addition, this article reviews current applications in chemistry and biology, and discuss advantages of droplet based microfluidics compared with conventional manner.

• KSBB Journal
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• v.29 no.4
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• pp.278-284
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• 2014

We present microfluidic method to rapidly analyze the effect of temperature on the change of morphologies of Antarctic bacteria (Pseudoalteromonas sp., Shewanella vesiculosa, Shewanella sp., and Cellulophaga sp.). The microfluidic device is able to generate stable temperature gradient from 7 to$40^{\circ}C$ and dramatically reduce the number of experiments, experimental cost and labor, and amount of sample. Based on this approach, we found that specific bacteria transforming morphology into filament or elongated body strongly depends on cultivation temperature. Interestingly, we found that the morphologies of Pseudoalteromonas sp., Shewanella vesiculosa, Shewanella sp., and Cellulophaga sp. are elongated at below $25^{\circ}C$, above $20^{\circ}C$, above $15^{\circ}C$ and above $35^{\circ}C$, respectively. We envision the microfluidic device is a useful approach to analyze biological events with a high throughput manner.