Three-dimensional spheroid-forming lab-on-a-chip using micro-rotational flow

Ota, Hiroki; Yamamoto, Ryōichi; Deguchi, Kisaburo; Tanaka, Yuta; Kazoe, Yutaka; Sato, Yohei; Miki, Norihisa

doi:10.1016/j.snb.2009.11.061

Cited by 56 publications

(62 citation statements)

References 26 publications

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“…Because there are many beneficial size effects at the micro and nano scales, such as short mixing times, high efficiency in chemical reactions, and minute amounts of reagents and effluent liquids, micro/nano fluidic devices have been extensively studied for use in biomedical applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In particular, nano fluidic devices that contain nano channels can be used for separation and filtration [21], single-molecule detection [22][23][24][25][26], highly efficient PCR [27], chemical analysis [28,29] and nano-photonic sensors [30], with great help of development of nanofabrication technologies [31][32][33][34][35][36][37][38][39][40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Effects of Micromachining Processes on Electro-Osmotic Flow Mobility of Glass Surfaces

et al. 2013

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Silica glass is frequently used as a device material for micro/nano fluidic devices due to its excellent properties, such as transparency and chemical resistance. Wet etching by hydrofluoric acid and dry etching by neutral loop discharge (NLD) plasma etching are currently used to micromachine glass to form micro/nano fluidic channels. Electro-osmotic flow (EOF) is one of the most effective methods to drive liquids into the channels. EOF mobility is affected by a property of the micromachined glass surfaces, which includes surface roughness that is determined by the manufacturing processes. In this paper, we investigate the effect of micromaching processes on the glass surface topography and the EOF mobility. We prepared glass surfaces by either wet etching or by NLD plasma etching, investigated the surface topography using atomic force microscopy, and attempted to correlate it with EOF generated in the micro-channels of the machined glass. Experiments revealed that the EOF mobility strongly depends on the surface roughness, and therefore upon the fabrication process used. A particularly strong dependency was observed when the surface roughness was on the order of the electric double layer thickness or below. We believe that the correlation described in this paper can be of great help in the design of micro/nano fluidic devices.

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Section: Introductionmentioning

confidence: 99%

Effects of Micromachining Processes on Electro-Osmotic Flow Mobility of Glass Surfaces

et al. 2013

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“…Later studies showed further progress toward effective µ-PIV investigation of microvortices [20]. On the millimeter scales, Ota et al applied two parallel counter flows to generate circulation, and the associated µ-PIV work demonstrated rotational velocity profiles inside the chamber [25]. We present the first experimental data describing fluid velocity profiles of microvortices in a side chamber.…”

Section: Investigations Of Flow Profiles In Microvortex Systemsmentioning

confidence: 89%

Simulation and Experimental Characterization of Microscopically Accessible Hydrodynamic Microvortices

et al. 2012

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Abstract:Single-cell studies of phenotypic heterogeneity reveal more information about pathogenic processes than conventional bulk-cell analysis methods. By enabling high-resolution structural and functional imaging, a single-cell three-dimensional (3D) imaging system can be used to study basic biological processes and to diagnose diseases such as cancer at an early stage. One mechanism that such systems apply to accomplish 3D imaging is rotation of a single cell about a fixed axis. However, many cell rotation mechanisms require intricate and tedious microfabrication, or fail to provide a suitable environment for living cells. To address these and related challenges, we applied numerical simulation methods to design new microfluidic chambers capable of generating fluidic microvortices to rotate suspended cells. We then compared several microfluidic chip designs experimentally in terms of: (1) their ability to rotate biological cells in a stable and precise manner; and (2) their suitability, from a geometric standpoint, for microscopic cell imaging. We selected a design that incorporates a trapezoidal side chamber connected to a main flow channel because it provided well-controlled circulation and met imaging requirements. Micro particle-image velocimetry (micro-PIV) was used to provide a detailed characterization of flows in the new design. Simulated and experimental results OPEN ACCESSMicromachines 2012, 3 530 demonstrate that a trapezoidal side chamber represents a viable option for accomplishing controlled single cell rotation. Further, agreement between experimental and simulated results confirms that numerical simulation is an effective method for chamber design.

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“…These structures facilitate short-term [23,94], controllable and uniform diameter [22,95] and compact spheroid generation [32,92]. U-shaped microstructures either are actuated temporarily using pneumatics [91][92][93]96] or are fixed within the device [90,93].…”

Section: Microfluidic Methods For Spheroid Culturementioning

confidence: 99%

“…Other works have used acoustic tweezers [104], pyramid microwells [26], porous membranes [105] and microrotational flow [23] in µSFCs for more efficient spheroid formation. We have recently shown that electrospinning technique can be efficiently used to fabricate porous membrane [106] and incorporation of such membrane inside a microchip can give rise to the formation of three different cellular aggregates, namely, single cells, monolayer and spheroid-like tissue [107].…”

Section: Microfluidic Methods For Spheroid Culturementioning

confidence: 99%

“…These cell spheroids have all the features mentioned above except that some quantities differ among them including spheroid formation time, oxygen uptake and diffusion and hypoxia limit. For instance, oxygen diffusion limitations develop necrotic core in both cancerous and hepatic spheroids when the spheroid grows more than a specified diameter (e.g., 150-200 µm for hepatic cells and 500 µm for cancerous cells [23]). …”

Section: Introductionmentioning

confidence: 99%

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Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumour models. The complex tumour microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

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Three-dimensional spheroid-forming lab-on-a-chip using micro-rotational flow

Cited by 56 publications

References 26 publications

Effects of Micromachining Processes on Electro-Osmotic Flow Mobility of Glass Surfaces

Effects of Micromachining Processes on Electro-Osmotic Flow Mobility of Glass Surfaces

Simulation and Experimental Characterization of Microscopically Accessible Hydrodynamic Microvortices

Inventions and Innovations in Preclinical Platforms for Cancer Research

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