An Easy-to-Fabricate Microfluidic Shallow Trench Induced Three-Dimensional Cell Culturing and Imaging (STICI3D) Platform

Umut Can Coskun, Funda Kus, Ateeq Ur Rehman, Berna Morova, Merve Gulle, Hatice Baser, Demet Kul, Alper Kiraz, Kemal Baysal, Ahmet Erten*

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1 Atıf (Scopus)

Özet

Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable nature of the STICI3D platform makes it suitable for researchers interested in fabricating custom polydimethylsiloxane devices as well as those who are in need of ready-to-use plastic platforms. As such, STICI3Ds can be used in imaging cell-cell interactions, angiogenesis, semiquantitative analysis of drug response in cells, and measurement of transport through cell sheet barriers.

Orijinal dilİngilizce
Sayfa (başlangıç-bitiş)8281-8293
Sayfa sayısı13
DergiACS Omega
Hacim7
Basın numarası10
DOI'lar
Yayın durumuYayınlandı - 15 Mar 2022

Bibliyografik not

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

Finansman

This study was supported by The Scientific and Technological Research Council of Turkey (Grant No 119E138). The authors gratefully acknowledge use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget. The microscope images were captured using the microscopes in the Molecular Imaging Core Facility of KUTTAM. Computing resources used in this work were provided by the National Center for High Performance Computing of Turkey under Grant No. 1006212019. This study was supported by The Scientific and Technological Research Council of Turkey (Grant No 119E138). The authors gratefully acknowledge use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget. The microscope images were captured using the microscopes in the Molecular Imaging Core Facility of KUTTAM. Computing resources used in this work were provided by the National Center for High Performance Computing of Turkey under Grant No. 1006212019.

FinansörlerFinansör numarası
Koç University Research Center for Translational Medicine
Koç University Research Center for Translational Medicine
National Center for High Performance Computing of Turkey1006212019
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu119E138

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