• Journal of Biosystems Engineering
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• 제39권3호
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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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• 제41권1호
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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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• 제27권4호
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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.

• 한국정보통신학회논문지
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• 제17권2호
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• pp.447-452
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• 2013

미세유체소자(microfluidic device)는 미생물과 관련된 다양한 작업들에 대해서 정확한 제어를 제공할 수 있다. 본 논문에서는 미세유체 소자와 디지털 홀로그래피 마이크로스코피 기술로 구성된 시스템을 구성하고 미생물의 3D 이미징과 세그먼테이션을 설명한다. 각각의 미생물은 미세유체 채널을 통하여 흘러가며 홀로그래피 마이크로스코피가 홀로그램을 기록한다. 기록된 홀로그램은 Fresnel 변환을 통하여 컴퓨터적으로 복원되며, 복원된 영상의 위상성분을 이용하여 미생물의 위치 정보를 찾기 위한 세그먼테이션을 수행한다. 제안하는 방법의 유용함을 설명하기 위하여 광학 실험을 수행하고 그 결과를 나타내었다.

• 한국가시화정보학회지
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• 제16권1호
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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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• 제26권4호
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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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• 제12권4호
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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.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 2012년도 춘계학술대회 논문집
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• pp.515-516
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• 2012

• Korean Chemical Engineering Research
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• 제52권2호
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• pp.141-153
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• 2014

액적기반의 미세유체 시스템은 마이크로 시험관으로서 화학, 생물학 연구에 적용하기 위해 개발되었다. 미세유체 시스템에서 피코부피(picoliter)의 매우 작은 액적은 소형화된 시스템 내에서 잘 정형화 되고 구획화된 반응기로 제공되어 진다. 매우 작은 액적에서의 반응은 자동화된 초고속 대용량 스크리닝 시스템을 통하여 저가이면서 고효율적으로 수행될 수 있다. 본 총설에서는 액적 기반의 미세유체시스템의 기능들인 액적 형성, 정교한 액적 제어, 다양한 응용분야에 대해 소개하고자 한다. 또한 화학적, 생물학적 새로운 응용분야에 관해 알아보고, 기존의 방법과 비교하여 액적기반의 미세유체 시스템이 갖는 장점에 관해 논의하고자 한다.

• KSBB Journal
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• 제29권4호
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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.