Pumpless microfluidic device with open top cell culture under oscillatory shear stress
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Pumpless microfluidic device with open top cell culture under oscillatory shear stress Zhehuan Chen 1 & Jenny Zilberberg 2 & Woo Lee 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Here we developed a 96-well plate-based pumpless microfluidic device to mimic bidirectional oscillatory shear stress experienced by osteoblasts at the endosteal niche located at the interface between bone and bone marrow. The culture device was designed to be high-throughput with 32 open top culture chambers for convenient cell seeding and staining. Mathematical modeling was used to simulate the control of oscillatory shear stress with the peak stress in the range of 0.3 to 50 mPa. Osteoblasts, cultured under oscillatory shear stress, were found to be highly viable and significantly aligned along the direction of flow. The modeling and experimental results demonstrate for the first time that cells can be cultured under controllable oscillatory shear stress in the open top culture chamber and pumpless configurations. Keywords Pumpless . Open-top . Oscillatory shear stress . Endosteal niche
1 Introduction Dynamic cell culture provides an important means of mimicking mechanically dynamic microenvironments of native tissues. Various tools have been used for dynamic cell culture such as spinner flasks, shake flasks, rotating vessels, and bioreactors.(Reinwald et al. 2016) In particular, microfluidic devices have been developed for benefits such as reduction of cell and reagent usage, precise flow control, continuously refreshed culture medium for diminished waste accumulation, and effective sample washing.(Chen et al. 2011; Dhiman et al. 2019; Wang et al. 2017; Warrick et al. 2007) Despite these advantages, the high-throughput use of microfluidic culture devices has been limited due to several major challenges. Jenny Zilberberg and Woo Lee contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-020-00515-2) contains supplementary material, which is available to authorized users. * Woo Lee [email protected] 1
Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, NJ 07030, USA
2
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
First, cell seeding, placement, staining, and harvesting in microfluidic devices are typically conducted through closed microchannel passages and can often be problematic. For example, directly injecting cells into a microchannel often results in clogging due to cell aggregation. It is also quite difficult to insert a pipette tip into a microfluidic inlet while precisely controlling the placement of cell suspension to a designated culture area within the device. Cell staining can also be difficult since it requires fixation, permeabilization, and immunostaining with each procedure involving syringe-based injection,(Ong et al. 2017) pipette dispensing(Chen et al. 2019) or passive pumping(Komeya et al
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