• 분석과학
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• 제34권6호
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• pp.275-283
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• 2021

본 연구에서는 화학 물질의 급성 안자극 시험을 수행하기 위한 세포 기반 미세유체 칩의 개발과 응용에 관한 연구를 수행하였다. 포토리소그래피와 소프트리소그래피 공정을 이용하여 미세유체 칩을 제작하였으며, 칩은 배양 면적이 다른 3개의 세포 배양 구획으로 이루어져 있다. 세포 기반 안자극 시험은 토끼 각막 상피 세포를 사용하여 수행하였다. 미세유체 칩에 배양된 세포에 화학 물질 수용액을 처리한 후 일정한 간격으로 세포를 관찰하고, 생존율 곡선을 기반으로 세포 사멸에 대한 속도 상수를 계산하였다. 세포-세포 사이의 연접, 세포-기판 사이의 부착, 초기 세포 수 변화가 세포 사멸 속도에 미치는 영향을 조사하여 미세유체 칩의 성능을 검증하였다. 안자극 시험의 표준물질인 sodium dodecylsulfate (SDS) 수용액의 다양한 농도 조건에서 안자극 시험을 수행하였다. 화학 물질의 수용액에 300초 동안 노출시킨 세포의 생존율을 이용하여 안자극을 시험하였다. 최종적으로 미세유체 칩의 각 구획에 대한 가중치를 기반으로 독성 점수(toxicity score, TS) 산출식을 얻었다. 본 연구에서 개발한 세포 기반 미세유체 칩은 화장품과 제약에 사용되는 화학 물질의 안자극 시험에 활용될 수 있을 것이다.

• BioChip Journal
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• 제12권4호
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• pp.257-267
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• 2018

Inertial microfluidics has attracted significant attention in recent years due to its superior benefits of high throughput, precise control, simplicity, and low cost. Many inertial microfluidic applications have been demonstrated for physiological sample processing, clinical diagnostics, and environmental monitoring and cleanup. In this review, we discuss the fundamental mechanisms and principles of inertial migration and Dean flow, which are the basis of inertial microfluidics, and provide basic scaling laws for designing the inertial microfluidic devices. This will allow end-users with diverse backgrounds to more easily take advantage of the inertial microfluidic technologies in a wide range of applications. A variety of recent applications are also classified according to the structure of the microchannel: straight channels and curved channels. Finally, several future perspectives of employing fluid inertia in microfluidic-based cell sorting are discussed. Inertial microfluidics is still expected to be promising in the near future with more novel designs using various shapes of cross section, sheath flows with different viscosities, or technologies that target micron and submicron bioparticles.

• 한국가시화정보학회지
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• 제18권3호
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• pp.84-89
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• 2020

Cancer cells secrete angiogenic factors, and nearby vasculatures make new blood vessels essential for cancer development and metastasis in response to these soluble factors. Many efforts have been made to elucidate cancer-endothelial cell interactions in vitro. However, not much is known due to the lack of a suitable co-culture platform. Here, we introduce a 3D printing-based microfluidic system that mimics the in vivo-like cancer-endothelial cell interactions. The tumoroids and endothelial cells are co-cultured, physically separated by porous fibrin gel, allowing communication between two cell types through soluble factors. Using this microfluidic system, we were able to visualize new vessel formation induced by tumoroids of different origins, including liver, breast, and ovary. We confirmed that the ovarian tumoroids most induced angiogenesis while the other two cancer types suppressed it. Utilization of the proposed co-culture platform will help the researchers unveil the underlying mechanisms of the dynamic interplay between tumor and angiogenesis.

• 센서학회지
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• 제17권4호
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• pp.245-249
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• 2008

This paper presents a microfluidic cell sizing method using hydrophoretic size-based separation. By exploiting slanted obstacles in a microchannel, we can generate a lateral pressure gradient so that microparticles can be deflected and arranged along lateral flows induced by the gradient. Using such movement of particles, we discriminated 8 to 15 μm-sized beads. We measured the size of U937 cells by comparing the hydrophoretic response of the cells to those of the size-standard beads whose diameters are known. Due to its simple design and fabrication, the sizing method can be easily integrated with other microfluidic components such as cell culture chambers conducting on-chip sizing and sorting.

• 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.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2003년도 ICCAS
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• pp.2457-2460
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• 2003

There is a great demand to manipulate biological cell autonomously since biologist should spend much time to obtain skillful manipulation techniques. For this purpose, we propose a cell chip to control, carry, fix and locate the cell. In this paper, we focus on the cell rotator to rotate individual biological cell based on a micro fluidics technology. The cell rotator consists of injection hole and rotation well to rotate a biological cell properly. Under the variation of flow rate in injection hole, the angular velocity of a biological cell is evaluated to find the feasibility of the proposed rotation method. As a practical experiment, Zebrafish egg is employed. Based on this research, we find the possibility of non-contact rotation way that can highly reduce the damage of the biological cell during manipulation. To realize an autonomous biological cell manipulation, a cell chip with manipulation well and micro channel in this research will be utilized effectively in near future.

• Bulletin of the Korean Chemical Society
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• 제34권4호
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• pp.1175-1180
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• 2013

A microfabricated electrochemical cell comprising PDMS-based microchannel and in-channel gold microelectrodes was fabricated as a sensitive and a miniature alternative to the conventional electroanalytical systems. A reproducible fabrication procedure enabled patterning of multiple microelectrodes integrated within a PDMS-based fluidic network. The active area of each electrode was $200{\mu}m{\times}200{\mu}m$ with a gap of $200{\mu}m$ between the electrodes which resulted in a higher signal to noise ratio. Also, the PDMS layer served the purpose of shielding the electrical interferences to the measurements. Analytes such as potassium ferrocyanide; amino acid: cysteine and nucleoside: guanosine were characterized using the fabricated cell. The microchip was comparable to bulk electrochemical systems and its applicability was also demonstrated with flow injection based rapid amperometric detection of DNA samples. The device so developed shall find use as a disposable electrochemical cell for rapid and sensitive analysis of electroactive species in various industrial and research applications.

• Design & Manufacturing
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• 제15권2호
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• pp.11-16
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• 2021

Recently, three-dimensional (3D) cell culture systems, which are superior to conventional two-dimensional (2D) vascular systems that mimic the in vivo environment, are being actively studied to reproduce drug responses and cell differentiation in organisms. Conventional two-dimensional cell culture methods (scaffold-based and non-scaffold-based) have a limited cell growth rate because the culture cannot supply the culture medium as consistently as microvessels. To solve this problem, we would like to propose a 3D culture system with an environment similar to living cells by continuously supplying the culture medium to the bottom of the 3D cell support. The 3D culture system is a structure in which microvascular structures are combined under a scaffold (agar, collagen, etc.) where cells can settle and grow. First, we have manufactured molds for the formation of four types of microvessel-mimicking chips: width / height ①100 ㎛ / 100 ㎛, ②100 ㎛ / 50 ㎛, ③ 150 ㎛ / 100 ㎛, and ④ 200 ㎛ / 100 ㎛. By injection molding, four types of microfluidic chips were made with GPPS (general purpose polystyrene), and a 100㎛-thick PDMS (polydimethylsiloxane) film was attached to the top of each microfluidic chip. As a result of observing the flow of the culture medium in the microchannel, it was confirmed that when the aspect ratio (height/width) of the microchannel is 1.5 or more, the fluid flows from the inlet to the outlet without a backflow phenomenon. In addition, the culture efficiency experiments of colorectal cancer cells (SW490) were performed in a 3D culture system in which PDMS films with different pore diameters (1/25/45 ㎛) were combined on a microfluidic chip. As a result, it was found that the cell growth rate increased up to 1.3 times and the cell death rate decreased by 71% as a result of the 3D culture system having a hole membrane with a diameter of 10 ㎛ or more compared to the conventional commercial. Based on the results of this study, it is possible to expand and build various 3D cell culture systems that can maximize cell culture efficiency by cell type by adjusting the shape of the microchannel, the size of the film hole, and the flow rate of the inlet.

• BMB Reports
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• 제44권11호
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• pp.705-712
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• 2011

Advances in the fields of proteomics and genomics have necessitated the development of high-throughput screening methods (HTS) for the systematic transformation of large amounts of biological/chemical data into an organized database of knowledge. Microfluidic systems are ideally suited for high-throughput biochemical experimentation since they offer high analytical throughput, consume minute quantities of expensive biological reagents, exhibit superior sensitivity and functionality compared to traditional micro-array techniques and can be integrated within complex experimental work flows. A range of basic biochemical and molecular biological operations have been transferred to chip-based microfluidic formats over the last decade, including gene sequencing, emulsion PCR, immunoassays, electrophoresis, cell-based assays, expression cloning and macromolecule blotting. In this review, we highlight some of the recent advances in the application of microfluidics to biochemistry and molecular biology.

• Smart Structures and Systems
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• 제12권1호
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• pp.1-22
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• 2013

Magnetic nanoparticle based bioseparation in microfluidics is a multiphysics phenomenon that involves interplay of various parameters. The ability to understand the dynamics of these parameters is a prerequisite for designing and developing more efficient magnetic cell/bio-particle separation systems. Therefore, in this work proof-of-concept experiments are combined with advanced numerical simulation to design and optimize the capturing process of magnetic nanoparticles responsible for efficient microfluidic bioseparation. A low cost generic microfluidic platform was developed using a novel micromolding method that can be done without a clean room techniques and at much lower cost and time. Parametric analysis using both experiments and theoretical predictions were performed. It was found that flow rate and magnetic field strength greatly influence the transport of magnetic nanoparticles in the microchannel and control the capturing efficiency. The results from mathematical model agree very well with experiments. The model further demonstrated that a 12% increase in capturing efficiency can be achieved by introducing of iron-grooved bar in the microfluidic setup that resulted in increase in magnetic field gradient. The numerical simulations were helpful in testing and optimizing key design parameters. Overall, this work demonstrated that a simple low cost experimental proof-of-concept setup can be synchronized with advanced numerical simulation not only to enhance the functional performance of magneto-fluidic capturing systems but also to efficiently design and develop microfluidic bioseparation systems for biomedical applications.