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This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested rather than microchip method. Analyte categories for which examples are presented include (i) drugs (quality control, seizures) and explosives residues, (ii) drugs and endogenous small molecules and ions in biofluids, (iii) proteins and peptides, and (iv) analysis of nucleic acids and oligonucleotides. Few cases of microchip analysis of physiological samples or other "real-world" matrices were found. However, many of the examples presented have potential application for these samples, especially with ongoing parallel developments involving integration of sample pretreatment onto chips and the use of fluid propulsion mechanisms other than electrokinetic pumping.

The organ-on-a-chip (OoC) is an intriguing scientific and technological development in which biology is coupled with microtechnology 1,2 to mimic key aspects of human physiology. The chip takes the form of a microfluidic device containing networks of hair-fine microchannels for guiding and manipulating minute volumes (picolitres up to millilitres) of solution [3][4][5] . The organ is a more relatable term that refers to the miniature tissues grown and residing in the microfluidic chips, which can recapitulate one or more tissue-specific functions. Although they are much simpler than native tissues and organs, scientists have discovered that these systems can often serve as effective mimics of human physiology and disease. OoCs comprise advanced in vitro technology that enables experimentation with biological cells and tissues outside the body. This is achieved by containing them inside vessels conditioned to sustain a reasonable semblance of the in vivo environment, from a biochemical and physical point of view. Working on the microscale lends a unique opportunity to attain a higher level of control over the microenvironment that ensures tissue life support, as well as a means to directly observe cell and tissue behaviour.The OoC is a relatively recent addition to the toolbox of model biological systems available to life science researchers to probe aspects of human pathophysiology and disease. These systems cover a spectrum of physiological relevance, with 2D cell cultures the least relevant, followed in increasing order by 3D cell cultures, organoids and OoCs. Unsurprisingly, the use of model organisms such as mice and Drosophila physiologically exceeds engineered tissue approaches 6,7 . While biological complexity increases with physiological relevance in model organisms, this unfortunately leads to increased experimental difficulty. In vivo physiological processes are, in many ways, the least accessible to direct investigation in mice, humans and other mammals, despite significant advances in in vivo imaging. However, 2D and 3D cell cultures, such as spheroids and stem cell-derived organoids, sacrifice some aspects of in vivo relevance to facilitate experimentation. The OoC may be regarded as a bridging technology, offering the ability to work with complex cell cultures, while providing better engineered microenvironments to maximize the model.Following on from early concepts, including animal-on-a-chip 8 , body-on-a-chip 9 and breathing lung-on-a-chip 10 , research in the OoC and microphysiological systems fields has grown exponentially; evidenced by numerous excellent reviews published recently 1,2,11 . Recognition of OoC technology now extends far beyond university laboratories, driven by a need to better understand the human physiology underlying health and disease, and to find new approaches to improve the human condition. The World Economic Forum, for instance, selected the OoC as one of the top ten emerging technologies in 2016 (ref. 12

The use of planar fluidic devices for performing small-volume chemistry was first proposed by analytical chemists, who coined the term "miniaturized total chemical analysis systems" (TAS) for this concept. More recently, the TAS field has begun to encompass other areas of chemistry and biology. To reflect this expanded scope, the broader terms "microfluidics" and "lab-on-a-chip" are now often used in addition to TAS. Most microfluidics researchers rely on micromachining technologies at least to some extent to produce microflow systems based on interconnected micrometer-dimensioned channels. As members of the microelectromechanical systems (MEMS) community know, however, one can do more with these techniques. It is possible to impart higher levels of functionality by making features in different materials and at different levels within a microfluidic device. Increasingly, researchers have considered how to integrate electrical or electrochemical function into chips for purposes as diverse as heating, temperature sensing, electrochemical detection, and pumping. MEMS processes applied to new materials have also resulted in new approaches for fabrication of microchannels. This review paper explores these and other developments that have emerged from the increasing interaction between the MEMS and microfluidics worlds.