Microfluidic cell cultures are ideally positioned to become the next generation of in vitro diagnostic tools for biomedical research, where key biological processes such as cell signalling and dynamic cell-to-cell interactions can be reliably analysed under reproducible physiological cell culture conditions. In the last decade, a large number of microfluidic cell analysis systems have been developed for a variety of applications including drug target optimization, drug screening and toxicological testing. More recently, advanced in vitro microfluidic cell culture systems have emerged that are capable of replicating the complex three-dimensional architectures of tissues and organs and thus represent valid biological models for investigating the mechanism and function of human tissue structures, as well as studying the onset and progression of diseases such as cancer. In this review, we present the most important developments in single-cell, 2D and 3D microfluidic cell culture systems for studying cell-to-cell interactions published over the last 6 years, with a focus on cancer research and immunotherapy, vascular models and neuroscience. In addition, the current technological development of microdevices with more advanced physiological cell microenvironments that integrate multiple organ models, namely, the so-called body-, human- and multi-organ-on-a-chip, is reviewed.
Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics.
In this study we have investigated a photosensitive thermoset (OSTEMER 322-40) as a complementary material to readily fabricate complex multi-layered microdevices for applications in life science. Simple, versatile and robust fabrication of multifunctional microfluidics is becoming increasingly important for the development of customized tissue-, organ- and body-on-a-chip systems capable of mimicking tissue interfaces and biological barriers. In the present work key material properties including optical properties, vapor permeability, hydrophilicity and biocompatibility are evaluated for cell-based assays using fibroblasts, endothelial cells and mesenchymal stem cells. The excellent bonding strength of the OSTEMER thermoset to flexible fluoropolymer (FEP) sheets and poly(dimethylsiloxane) (PDMS) membranes further allows for the fabrication of integrated microfluidic components such as membrane-based microdegassers, microvalves and micropumps. We demonstrate the application of multi-layered, membrane-integrated microdevices that consist of up to seven layers and three membranes that specially confine and separate vascular cells from the epithelial barrier and 3D tissue structures.
In this work we present a high resolution oxygen imaging approach, which can be used to study 2D oxygen distribution inside microfluidic environments. The presented setup comprises a fabrication process of microfluidic chips with integrated luminescent sensing films combined with referenced oxygen imaging applying a color CCD-camera. Enhancement of the sensor performance was achieved by applying the principle of light harvesting. This principle enabled ratiometric imaging employing the red and the green channel of a color CCD-camera. The oxygen sensitive emission of platinum(ii)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin (PtTFPP) was detected by the red channel, while the emission of a reference dye was detected by the green channel. This measurement setup allowed for accurate real-time 2D oxygen imaging with superior quality compared to intensity imaging. The sensor films were subsequently used to measure the respiratory activity of human cell cultures (HeLa carcinoma cells and normal human dermal fibroblasts) in a microfluidic system. The sensor setup is well suited for different applications from spatially and temporally resolving oxygen concentration inside microfluidic channels to parallelization of oxygen measurements and paves the way to novel cell based assays, e.g. in tissue engineering, tumor biology and hypoxia reperfusion phenomena.
The human placenta plays a crucial role as the interface between mother and fetus. It represents a unique tissue that undergoes morphological as well as functional changes on the cellular and tissue level throughout pregnancy. To better understand how the placenta works, a variety of techniques has been developed to re-create this complex physiological barrier in vitro. However, due to the low availability of freshly isolated primary cells, choriocarcinoma cell lines remain the usual suspects as in vitro models for placental research. Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model.
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