The use of organoids is emerging as a promising technology to mimic accurately both human physiology and human pathologies, with interesting opportunities for drug discovery and preclinical toxicology. As a part of the organoid, stem cells and differentiated components are strictly regulated and are able to interact with the surrounding microenvironment provided by the culture medium. Organoids are 3D cellular clusters derived from stem cells or progenitor cells that self-organize in an artificial extracellular matrix and are spatially and dynamically similar to their in vivo counterparts. Furthermore, this technology allows for the study of complex systems by reproducing the realistic micro-anatomy and activities, mechanics, and physiological response of specific organs (organs- and organoids-on-a-chip), therefore allowing the shift from flat two-dimensional (2D) cell-based systems to more complex and sensible three-dimensional (3D) architectures. Representative applications include the simulation of cellular responses that mimic the in vivo environment, such as relaxed or constricted blood vessels, the ability to grow and manipulate a single or group of cells within a specific compartment of the chip, and the possibility to integrate on-line sample preparation and subsequent analysis. Microfluidic devices offer many advantages for the analysis of the content of single or multiple cells compared to standard methods (e.g., flow cytometry, cell imaging, liquid chromatography, and CE). The increased interest of the research community for these technologies is supported by thousands of publications in peer-reviewed journals and conference proceedings. Since then, the number and types of microfluidic-based technologies have dramatically increased and they have been applied in a number of fields including chemistry, biochemistry, physics, biology, and molecular biology. Approximately 10 years later, Manz and co-workers published a paper describing the use of micromachining to build up a miniaturized total chemical analysis system, laying the foundations for the development of an integrated microfluidic system using capillary electrophoresis (CE). described a miniature gas analysis system fabricated out of silicon. The development of the first microchip instrument goes back to 1979, when Terry et al. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies.Īs it has been described about 15 years ago by Whitesides, “microfluidic is the science and technology of systems that process or manipulate small (10 −9 to 10 −18 L) amounts of fluids, using channels with dimensions of tens to hundreds of micrometres”. Finally, the integration of microfluidics with recent innovative technologies-such as organoids, organ-on-chip, and 3D printing-for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids.

We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’.

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