Simultaneous generation of chemical concentration and mechanical shear stress gradients using microfluidic osmotic flow comparable to interstitial flow

Park, Joong Yull,Yoo, Sung Ju,Hwang, Chang Mo,Lee, Sang-Hoon Royal Society of Chemistry 2009 Lab on a chip Vol.9 No.15

<P>Cells are very sensitive to various microenvironmental cues, including mechanical stress and chemical gradients. Therefore, physiologically relevant models of cells should consider how cells sense and respond to microenvironmental cues. This can be accomplished by using microfluidic systems, in which fluid physics can be realized at a nanoliter scale. Here we describe a simple and versatile method to study the generation of chemical concentration and mechanical shear stress gradients in a single microfluidic chip. Our system uses an osmotic pump that produces very slow (<a few µm/s) and controlled flow, allowing a wide and stable diffusion of specific chemical concentration. We also established a shear stress gradient passively <I>via</I> a circular channel in the interstitial level. For evaluation of the system, we used L929 mouse fibroblast cells and simultaneously exposed them to a mechanical stress gradient and a chemical nutrient gradient. The interstitial shear stress level clearly affected cell alignment, mobility velocity, and attachment. At the same time, cell proliferation reflected nutrient concentration level. Our system, which enables continuous and long-term culture of cells in a combined chemical and mechanical gradient, provides physiologically realistic conditions and will be applicable to studies of cancer metastasis and stem cell differentiation.</P> <P>Graphic Abstract</P><P>The generation of chemical concentration and mechanical shear stress gradients was achieved in a single microfluidic chip. The interstitial level of flow affected cell alignment, mobility, and attachment. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b822006a'> </P>

Differentiation of Neural Progenitor Cells in a Microfluidic Chip-Generated Cytokine Gradient

Park, Joong Yull,Kim, Suel-Kee,Woo, Dong-Hun,Lee, Eun-Joong,Kim, Jong-Hoon,Lee, Sang-Hoon Wiley (John WileySons) 2009 Stem Cells Vol.27 No.11

<P>In early embryonic development, spatial gradients of diffusible signaling molecules play important roles in controlling differentiation of cell types or arrays in diverse tissues. Thus, the concentration of exogenous cytokines or growth factors at any given time is crucial to the formation of an enriched population of a desired cell type from primitive stem cells in vitro. Microfluidic technology has proven very useful in the creation of cell-friendly microenvironments. Such techniques are, however, currently limited to a few cell types. Improved versatility is required if these systems are to become practically applicable to stem cells showing various plasticity ranges. Here, we built a microfluidic platform in which cells can be exposed to stable concentration gradients of various signaling molecules for more than a week with only minimal handling and no external power source. To maintain stability of the gradient concentration, the osmotic pumping performance was optimized by balancing the capillary action and hydraulic pressure in the inlet reagent reservoirs. We cultured an enriched population of neural progenitors derived from human embryonic stem cells in our microfluidic chamber for 8 days under continuous cytokine gradients (sonic hedgehog, fibroblast growth factor 8, and bone morphogenetic protein 4). Neural progenitors successfully differentiated into neurons, generating a complex neural network. The average numbers of both neuronal cell body clusters and neurite bundles were directly proportional to sonic hedgehog concentrations in the gradient chip. The system was shown to be useful for both basic and translational research, with straightforward mechanisms and operational schemes.</P>

Regulating microenvironmental stimuli for stem cells and cancer cells using microsystems

Park, Joong Yull,Takayama, Shuichi,Lee, Sang-Hoon Royal Society of Chemistry 2010 Integrative biology Vol.2 No.5

<P>Cells express hundreds of different types of receptors, which they use to continuously monitor their chemical and mechanical microenvironments. Stem cells and cancer cells are particularly sensitive to microenvironmental cues because their interactions have profound effects on stem cell potency and tumorigenesis, respectively. Unlike conventional tissue culture in wells and dishes, microtechnology with dimensions on the cellular scale can be combined with materials, chemicals, physiological flows, and other effectors to provide high levels of control in a format more flexible than macroscale <I>in vitro</I> or <I>in vivo</I> systems, revealing stimulation-specific responses of stem cells and cancer cells. Microtechnology-integrated biology enable the simultaneous control of multiple numbers of biological microenvironmental factors in a high-throughput manner. In this review we present representative examples of the use of microtechnology systems to regulate the mechanical, chemical, topological, adhesive, and other environments of individual stem cells and cancer cells. We then explore the possibilities for simultaneous multimodal control of combinations of these environmental factors.</P> <P>Graphic Abstract</P><P>Microtechnology in regulating single or multiple biological stimuli will offer great opportunities to reveal new cellular behaviors for stem cell and cancer research. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c000442a'> </P>

Ice-lithographic fabrication of concave microwells and a microfluidic network

Park, Joong Yull,Hwang, Chang Mo,Lee, Sang-Hoon Springer-Verlag 2009 Biomedical microdevices Vol.11 No.1

Study of cellular behaviors on concave and convex microstructures fabricated from elastic PDMS membranes

Park, Joong Yull,Lee, Dae Ho,Lee, Eun Joong,Lee, Sang-Hoon Royal Society of Chemistry 2009 Lab on a chip Vol.9 No.14

<P>Cells respond to geometrical cues, as well as to biochemical and mechanical stimuli. Recent progress in micro- and nano-technology has allowed researchers to create microbeads, micro-circular islands, and microposts, that can be used to examine the effect of geometrical cues on cellular behavior. Knowledge of changes in cell mechanics and morphology in response to geometric cues is important for understanding the basic behavior of cells during development and pathological processes. Most previous research in this area has focused on cell responses to two-dimensional planar or rectilinear structures. Very few studies have examined cell responses to three-dimensional curved structures because of the difficulty of fabricating such microstructures. Here we describe a novel method for the fabrication of convex and concave microstructures by use of a thin poly(dimethylsiloxane) (PDMS) membrane, SU-8 shadow mask, and negative air pressure without using any complicated silicon processes. We successfully fabricated concave and convex microstructures, with base diameters of 200–300 µm and depth (or height) of 50–150 µm (aspect ratios up to 1 : 0.5), and used these microstructures to study the responses of cultured L929 mouse fibroblast cells and human mesenchymal stem cells. These cells clearly sensed the three-dimensional microscale curvature and actively “escaped” from concave patterns, but not from those which were convex. Thus, it appears that microscale concave structures suppress cell adhesion and proliferation. We hypothesized that this might relate to deformation of the plasma membrane and subsequent opening of membrane channels. We anticipate that our system will be useful for various bio-MEMS (micro electro mechanical system) applications, including formation of uniformly-sized embryoid bodies, embryonic stem cell differentiation, and the fabrication of cell docking devices, microbioreactors, and microlenses as well as cell mechanics study.</P> <P>Graphic Abstract</P><P>We successfully fabricated concave and convex microstructures, and used these microstructures to study the responses of cultured fibroblast cells (<I>left</I>) and human mesenchymal stem cells (<I>right</I>). These cells clearly sensed the three-dimensional microscale curvature and actively “escaped” from concave patterns. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b820955c'> </P>

마이크로 유체 칩을 이용한 세포행태에 관한 연구

박중열(Joong Yull Park),이상훈(Sang-Hoon Lee) 대한기계학회 2008 대한기계학회 춘추학술대회 Vol.2008 No.11

In the conventional biology, the most of cell studies was carried out by culturing cells in the Petri dish and by investigating cellular behavior under the diverse bio-molecule (cell signalling materials, drugs or etc.) conditions. However, in vivo environments, diverse stimulations including chemical, mechanical and topological environments involved in the proliferation, differentiation and migration of cells and it is almost impossible to provide these conditions with traditional method. We have developed the methods to provide the well defined chemical and mechanical stimulations using microfluidic devices and applied these approaches to the study of environmental effect on cells. In this paper, we will introduce our microfluidic chips to provide microenvironment and its applications using several cells.

코로나19로 촉발된 비대면 교육의 대규모 확장

박중열(Joong Yull Park) 대한기계학회 2021 대한기계학회 논문집. Transactions of the KSME. C, 산업기술과 혁신 Vol.9 No.1

코로나19는 전 세계적으로 사회적, 경제적, 심리적 그리고 다른 모든 면에서 현재 진행형으로 크고 작은 영향을 미치고 있으며 당연히 대학의 교육에도 큰 영향을 가져왔다. 대표적인 것은 전통적인 대면 교육을 포기하고 대체 방안인 비대면 온라인 교육으로 전환한 것이다. 이에 온라인 교육의 특징과 학생들의 반응을 알아보았다. 코로나19의 범세계적 유행이 지나간 후에는 대학 교육에 대한 인식 변화는 필연적일 것이다. 특히, 교 · 강사와 학생들 모두가 온라인 교육의 본질에 대한 이해가 강화되고 깊어지고 있다. 이것은 온라인 교육을 보다 바람직한 방향으로 발전시킬 수 있는 원동력이 될 것이다. 미래에 전통적 대면 교육과 온라인 교육이 조화롭게 융합되어 새롭고 더 우수한 교육 형태로 거듭나기를 기대한다. COVID-19 is now affecting society, economics, psychology, and all other aspects globally, and has also had a major impact on university education. Most notable is the transition from traditional face-to-face training to non-face-to-face online training. Therefore, the characteristics of online education and the report on students" responses are introduced. After the pandemic of COVID-19 has passed, a change in perception of university education will be inevitable. In particular, both teachers and students are strengthening and deepening their understanding of the nature of online education. This will be the driving force to advance online education in a more desirable direction. In the future, it is hoped that traditional face-to-face education and online education will be harmoniously integrated and reborn as a new and superior form of education.

Open Sandwich FRET Immunoassay of Estrogen Receptor β in a PDMS Microfluidic Channel

Park, Hye-Jin,Lee, Moon-Kwon,Seong, Gi-Hun,Choo, Jae-Bum,Lee, Eun-Kyu,Park, Joong-Yull,Lee, Sang-Hoon,Lee, Kyeong-Hee,Choi, Young-Wook Korean Chemical Society 2008 Bulletin of the Korean Chemical Society Vol.29 No.7

Hypergravity-induced multicellular spheroid generation with different morphological patterns precisely controlled on a centrifugal microfluidic platform

Park, Jiheum,Lee, Gi-Hun,Yull Park, Joong,Lee, Jung Chan,Kim, Hee Chan IOP Publishing 2017 Biofabrication Vol.9 No.4

A numerical study of the Coriolis effect in centrifugal microfluidics with different channel arrangements

Park, Jiheum,Lee, Gi-Hun,Park, Joong Yull,Lee, Jung Chan,Kim, Hee Chan Springer-Verlag 2016 MICROFLUIDICS AND NANOFLUIDICS Vol.20 No.4