Abstract
AbstractTwo‐dimensional (2D) cell cultures have been the primary screening tools to predict drug impacts in vitro for decades. However, owing to the lack of tissue‐specific architecture of 2D cultures, secondary screening using three‐dimensional (3D) cell culture models is often necessary. A microfluidic approach that facilitates side‐by‐side 2D and 3D cell culturing in a single microchannel and thus combines the benefits of both set‐ups in drug screening; that is, the uniform spatiotemporal distributions of oxygen, nutrients, and metabolic wastes in 2D, and the tissue‐like architecture, cell–cell, and cell–extracellular matrix interactions only achieved in 3D. The microfluidic platform is made from an organically modified ceramic material, which is inherently biocompatible and supports cell adhesion (2D culture) and metal adhesion (for integration of impedance electrodes to monitor cell proliferation). To induce 3D spheroid formation on another area, a single‐step lithography process is used to fabricate concave microwells, which are made cell‐repellant by nanofunctionalization (i.e., plasma porosification and hydrophobic coating). Thanks to the concave shape of the microwells, the spheroids produced on‐chip can also be released, with the help of microfluidic flow, for further off‐chip characterization after culturing. In this study, the methodology is evaluated for drug cytotoxicity assessment on human hepatocytes.
Highlights
The increasing focal length and consequent lightDr P
We describe a microfabrication method, which facilitates straightforward implementation of U-shaped microwells for production of small 3D cell spheroids under microfluidic flow
The microfluidic control of growth conditions is achieved by sealing the Ormocomp platform with a gas-permeable polydimethylsiloxane (PDMS) channel (200 μm × 3 mm × 30 mm, height × width × length) (Figure 1a–c)
Summary
Jokinen Department of Chemistry and Materials Science School of Chemical Engineering Aalto University Tietotie 3, Espoo 02150, Finland spatiotemporal control over the culture conditions, microfluidics enables improved supply of nutrients and oxygen, and efficient removal of metabolic waste. These factors have immediate impacts on both the cell health and the accuracy of the in vitro-in vivo prediction of drug effects. We describe a microfabrication method, which facilitates straightforward implementation of U-shaped microwells for production of small 3D cell spheroids under microfluidic flow. The concept was applied to drug cytotoxicity evaluation with the help of paclitaxel, a known hepatotoxic anticancer drug
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