Simultaneous Culturing of Cell Monolayers and Spheroids on a Single Microfluidic Device for Bridging the Gap between 2D and 3D Cell Assays in Drug Research

Two‐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.Peer reviewe

Mechanistic study of oxygen-scavenging properties of off-stoichiometric thiol-enes

Peer reviewe

Understanding Cell Proliferation and Material induced Cell Death on Microfluidic Devices Made of Off Stoichiometric Thiol enes

Peer reviewe

Inkjet Printed Silver Electrodes on Macroporous Paper for a Paper-Based Isoelectric Focusing Device

We demonstrate a combined printing process utilizing inkjet printing of silver electrodes and solid-ink technology for printing hydrophobic wax barriers for fabricating paper microfluidic devices with integrated electrodes. Optimized printing parameters are given for achieving conducting silver lines on the top of macroporous chromatography paper down to 250 mu m-300 mu m resolution. Electrical characterization and wicking experiments demonstrate that the printed silver patterns are simultaneously conductive and porous enough to allow reliable capillary wicking across the electrodes. The combined wax and silver printing method is used for fabrication of paper microfluidic isoelectric focusing devices for separation and concentration of proteins. Published by AIP Publishing.Peer reviewe

Ympäristön lääkejäämät: toivoa on, tietoa vain rajallisesti : Pharmaceuticals in the Environment

Non peer reviewe

Fish-Liver-on-Chip: A Microfluidic Model to Assess Bioaccumulation of Environmental Drug Residues In Vitro

Peer reviewe

Cytochrome P450 Inhibition by Antimicrobials and Their Mixtures in Rainbow Trout Liver Microsomes In Vitro

Antimicrobials are ubiquitous in the environment and can bioaccumulate in fish. In the present study, we determined the half-maximal inhibitory concentrations (IC50) of 7 environmentally abundant antimicrobials (ciprofloxacin, clarithromycin, clotrimazole, erythromycin, ketoconazole, miconazole, and sulfamethoxazole) on the cytochrome P450 (CYP) system in rainbow trout (Oncorhynchus mykiss) liver microsomes, using 7-ethoxyresorufin O-deethylation (EROD, CYP1A) and 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD, CYP3A) as model reactions. Apart from ciprofloxacin and sulfamethoxazole, all antimicrobials inhibited either EROD or BFCOD activities or both at concentrationsPeer reviewe

Microfluidic oxygen tolerability screening of nanocarriers for triplet fusion photon upconversion

The full potential of triplet fusion photon upconversion (TF-UC) of providing high-energy photons locally with low-energy excitation is limited in biomedicine and life sciences by its oxygen sensitivity. This hampers the applicability of TF-UC systems in sensors, imaging, optogenetics and drug release. Despite the advances in improving the oxygen tolerability of TF-UC systems, the evaluation of oxygen tolerability is based on comparing the performance at completely deoxygenated (0% oxygen) and ambient (20-21%) conditions, leaving the physiological oxygen levels (0.3-13.5%) neglected. This oversight is not deliberate and is only the result of the lack of simple and predictable methods to obtain and maintain these physiological oxygen levels in an optical setup. Herein, we demonstrate the use of microfluidic chips made of oxygen depleting materials to study the oxygen tolerability of four different micellar nanocarriers made of FDA-approved materials with various oxygen scavenging capabilities by screening their TF-UC performance over physiological oxygen levels. All nanocarriers were capable of efficient TF-UC even in ambient conditions. However, utilizing oxygen scavengers in the oil phase of the nanocarrier improves the oxygen tolerability considerably. For example, at the mean tumour oxygen level (1.4%), nanocarriers made of surfactants and oil phase both capable of oxygen scavenging retained remarkably 80% of their TF-UC emission. This microfluidic concept enables faster, simpler and more realistic evaluation of, not only TF-UC, but any micro or nanoscale oxygen-sensitive system and facilitates their development and implementation in biomedical and life science applications.Peer reviewe

Cell adhesion and proliferation on common 3D printing materials used in stereolithography of microfluidic devices

Three-dimensional (3D) printing has recently emerged as a cost-effective alternative for rapid prototyping of microfluidic devices. The feature resolution of stereolithography-based 3D printing is particularly well suited for manufacturing of continuous flow cell culture platforms. Poor cell adhesion or material-induced cell death may, however, limit the introduction of new materials to microfluidic cell culture. In this work, we characterized four commercially available materials commonly used in stereolithography-based 3D printing with respect to long-term (2 month) cell survival on native 3D printed surfaces. Cell proliferation rates, along with material-induced effects on apoptosis and cell survival, were examined in mouse embryonic fibroblasts. Additionally, the feasibility of Dental SG (material with the most favored properties) for culturing of human hepatocytes and human-induced pluripotent stem cells was evaluated. The strength of cell adhesion to Dental SG was further examined over a shear force gradient of 1–89 dyne per cm² by using a custom-designed microfluidic shear force assay incorporating a 3D printed, tilted and tapered microchannel sealed with a polydimethylsiloxane lid. According to our results, autoclavation of the devices prior to cell seeding played the most important role in facilitating long-term cell survival on the native 3D printed surfaces with the shear force threshold in the range of 3–8 dyne per cm².Three-dimensional (3D) printing has recently emerged as a cost-effective alternative for rapid prototyping of microfluidic devices. The feature resolution of stereolithography-based 3D printing is particularly well suited for manufacturing of continuous flow cell culture platforms. Poor cell adhesion or material-induced cell death may, however, limit the introduction of new materials to microfluidic cell culture. In this work, we characterized four commercially available materials commonly used in stereolithography-based 3D printing with respect to long-term (2 month) cell survival on native 3D printed surfaces. Cell proliferation rates, along with material-induced effects on apoptosis and cell survival, were examined in mouse embryonic fibroblasts. Additionally, the feasibility of Dental SG (material with the most favored properties) for culturing of human hepatocytes and human-induced pluripotent stem cells was evaluated. The strength of cell adhesion to Dental SG was further examined over a shear force gradient of 1-89 dyne per cm(2)by using a custom-designed microfluidic shear force assay incorporating a 3D printed, tilted and tapered microchannel sealed with a polydimethylsiloxane lid. According to our results, autoclavation of the devices prior to cell seeding played the most important role in facilitating long-term cell survival on the native 3D printed surfaces with the shear force threshold in the range of 3-8 dyne per cm(2).Peer reviewe