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Article

A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array

1
School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore
2
Interdisciplinary Graduate School, Nanyang Technological University, Singapore 639798, Singapore
3
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
4
Endocrinology Department, Tan Tock Seng Hospital, Singapore 308433, Singapore
*
Author to whom correspondence should be addressed.
Biosensors 2021, 11(12), 509; https://doi.org/10.3390/bios11120509
Received: 17 October 2021 / Revised: 6 December 2021 / Accepted: 7 December 2021 / Published: 10 December 2021
(This article belongs to the Special Issue Bioinspired and Biobased Materials for Biosensor Applications)
Incorporation of extracellular matrix (ECM) and hydrogel in microfluidic 3D cell culture platforms is important to create a physiological microenvironment for cell morphogenesis and to establish 3D co-culture models by hydrogel compartmentalization. Here, we describe a simple and scalable ECM patterning method for microfluidic cell cultures by achieving hydrogel confinement due to the geometrical expansion of channel heights (stepped height features) and capillary burst valve (CBV) effects. We first demonstrate a sequential “pillar-free” hydrogel patterning to form adjacent hydrogel lanes in enclosed microfluidic devices, which can be further multiplexed with one to two stepped height features. Next, we developed a novel “spheroid-in-gel” culture device that integrates (1) an on-chip hanging drop spheroid culture and (2) a single “press-on” hydrogel confinement step for rapid ECM patterning in an open-channel microarray format. The initial formation of breast cancer (MCF-7) spheroids was achieved by hanging a drop culture on a patterned polydimethylsiloxane (PDMS) substrate. Single spheroids were then directly encapsulated on-chip in individual hydrogel islands at the same positions, thus, eliminating any manual spheroid handling and transferring steps. As a proof-of-concept to perform a spheroid co-culture, endothelial cell layer (HUVEC) was formed surrounding the spheroid-containing ECM region for drug testing studies. Overall, this developed stepped height-based hydrogel patterning method is simple to use in either enclosed microchannels or open surfaces and can be readily adapted for in-gel cultures of larger 3D cellular spheroids or microtissues. View Full-Text
Keywords: hydrogel patterning; 3D cell culture; organ-on-a-chip; microarray; spheroid culture hydrogel patterning; 3D cell culture; organ-on-a-chip; microarray; spheroid culture
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MDPI and ACS Style

Su, C.; Chuah, Y.J.; Ong, H.B.; Tay, H.M.; Dalan, R.; Hou, H.W. A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array. Biosensors 2021, 11, 509. https://doi.org/10.3390/bios11120509

AMA Style

Su C, Chuah YJ, Ong HB, Tay HM, Dalan R, Hou HW. A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array. Biosensors. 2021; 11(12):509. https://doi.org/10.3390/bios11120509

Chicago/Turabian Style

Su, Chengxun, Yon J. Chuah, Hong B. Ong, Hui M. Tay, Rinkoo Dalan, and Han W. Hou. 2021. "A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array" Biosensors 11, no. 12: 509. https://doi.org/10.3390/bios11120509

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