Abstract
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.
Highlights
For over two decades, the application of micromachining technologies for biomedical research has led to the development of miniaturized assays for advanced in vitro cell analysis in so-called cell-based microfluidic platforms
We present the latest developments in microfluidic co-culture systems for studies of cellto-cell interactions, with a focus on cancer research, vascular models, and neuroscience
Fundamental research aims to understand the biological processes behind cancer, tries to create relevant models by applying 3D cell culture techniques to microfluidic devices, and frequently includes drug testing
Summary
The application of micromachining technologies for biomedical research has led to the development of miniaturized assays for advanced in vitro cell analysis in so-called cell-based microfluidic platforms. Various types of target cell, including stromal, endothelial and immune cells, under physiologically relevant conditions.[2,38,43] Over the years, a variety of advanced microfluidic in vitro tumour models have been established for (i) the two-dimensional cultivation of tumour cells and (ii) the formation, as well as cultivation, of three-dimensional tumour structures (e.g., cell-laden hydrogels or spheroids).[5,44,45,46,47] More recently, the immunology of cancer has gained momentum owing to the emergence of cellbased immunotherapy as a promising complementary strategy for anticancer treatment. The authors demonstrated how non-invasive biosensors can be employed for the automation of assays of cell migration and tumour cell invasion on-chip, as they are highly sensitive to cell population responses without the need for cell staining or fluorescent transfection reagents
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