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This textbook provides a unique, pocket-sized, self-directed study guide to fluid, electrolyte and acid base homeostasis for undergraduate biomedical science, pharmacology, medical and allied health students. It details the chemical (mostly ionic) composition of body fluids, explains how abnormalities arise, what laboratory tests can be used to identify and analyze the cause of these disorders and shows how normality can be achieved to maintain health.

Peripheral biochemical monitoring involves the use of wearable devices for minimally invasive or noninvasive measurement of analytes in biofluids such as interstitial fluid, saliva, tears and sweat. The goal in most cases is to obtain measurements that serve as surrogates for circulating analyte concentrations in blood. Key technological developments to date include continuous glucose monitors, which use an indwelling sensor needle to measure glucose in interstitial fluid, and device-integrated sweat stimulation for continuous access to analytes in sweat. Further development of continuous sensing technologies through new electrochemical sensing modalities will be a major focus of future research. While there has been much investment in wearable technologies to sense analytes, less effort has been directed to understanding the physiology of biofluid secretion. Elucidating the underlying biology is crucial for accelerating technological progress, as the biofluid itself often presents the greatest challenge in terms of sample volumes, secretion rates, filtration, active analyte channels, variable pH and salinity, analyte breakdown and other confounding factors.Heikenfeld et al. survey the range of biochemical analytes that can be sensed in dermal interstitial fluid, saliva and sweat, and outline criteria for tailoring sensor design to address the right analyte in the right body site for the right disease or wellness application.

In nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment. Although microrobotic swarms are attractive for biomedical applications, controlling their collective movement in specific bio-fluids is difficult. Here, the authors report navigated locomotion and collective behaviors of magnetic field- and medium-induced micro-robotic swarms in various bio-fluids.

Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.Assessing progress towards designing reliable wearable biosensors reveals the challenges remaining before the promise of clinical translation can be realized.

Proteomes are characterized by large protein-abundance differences, cell-type- and time-dependent expression patterns and post-translational modifications, all of which carry biological information that is not accessible by genomics or transcriptomics. Here we present a mass-spectrometry-based draft of the human proteome and a public, high-performance, in-memory database for real-time analysis of terabytes of big data, called ProteomicsDB. The information assembled from human tissues, cell lines and body fluids enabled estimation of the size of the protein-coding genome, and identified organ-specific proteins and a large number of translated lincRNAs (long intergenic non-coding RNAs). Analysis of messenger RNA and protein-expression profiles of human tissues revealed conserved control of protein abundance, and integration of drug-sensitivity data enabled the identification of proteins predicting resistance or sensitivity. The proteome profiles also hold considerable promise for analysing the composition and stoichiometry of protein complexes. ProteomicsDB thus enables navigation of proteomes, provides biological insight and fosters the development of proteomic technology. A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance. Mapping the human proteome More than a decade after publication of the draft human genome sequence, there is no direct equivalent for the human proteome. But in this issue of Nature two groups present mass spectrometry-based analysis of human tissues, body fluids and cells mapping the large majority of the human proteome. Akhilesh Pandey and colleagues identified 17,294 protein-coding genes and provide evidence of tissue- and cell-restricted proteins through expression profiling. They highlight the importance of proteogenomic analysis by identifying translated proteins from annotated pseudogenes, non-coding RNAs and untranslated regions. The data set is available on http://www.humanproteomemap.org . Bernhard Kuster and colleagues have assembled protein evidence for 18,097 genes in ProteomicsDB (available on https://www.proteomicsdb.org ) and highlight the utility of the data, for example the identification of hundreds of translated lincRNAs, drug-sensitivity markers and discovering the quantitative relationship between mRNA and protein levels in tissues. Elsewhere in this issue, Vivien Marx reports on a third major proteomics project, the antibody-based Human Protein Atlas programme ( http://www.proteinatlas.org/ ).

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.

Crucial steps in the miniaturisation of biosensors are the conversion of a biological signal into an electrical current as well as the direct sampling of bodily fluids. Here we show that protein sensors in combination with a nanopore, acting as an electrical transducer, can accurately quantify metabolites in real time directly from nanoliter amounts of blood and other bodily fluids. Incorporation of the nanopore into portable electronic devices will allow developing sensitive, continuous, and non-invasive sensors for metabolites for point-of-care and home diagnostics. Protein nanopores are emerging as sensors for a variety of biomolecules. Here the authors develop a nanopore based on the bacterial toxin ClyA, in conjunction with binding proteins for glucose and asparagine, to detect these biomolecules simultaneously from a variety of unprocessed, diluted body fluids.

Bacteriophages are promising therapeutic agents that can be applied to different stages of the commercial food chain. In this sense, bacteriophages can be orally administered to farm animals to protect them against intestinal pathogens. However, the low pH of the stomach, the activities of bile and intestinal tract enzymes limit the efficacy of the phages. This study demonstrates the utility of an alginate/CaCO encapsulation method suitable for bacteriophages with different morphologies and to yield encapsulation efficacies of ~100%. For the first time, a cocktail of three alginate/CaCO -encapsulated bacteriophages was administered as oral therapy to commercial broilers infected with Salmonella under farm-like conditions. Encapsulation protects the bacteriophages against their destruction by the gastric juice. Phage release from capsules incubated in simulated intestinal fluid was also demonstrated, whereas encapsulation ensured sufficient intestinal retention of the phages. Moreover, the small size of the capsules (125-150 μm) enables their use in oral therapy and other applications in phage therapy. This study evidenced that a cocktail of the three alginate/CaCO -encapsulated bacteriophages had a greater and more durable efficacy than a cocktail of the corresponding non-encapsulated phages in as therapy in broilers against Salmonella, one of the most common foodborne pathogen.

Recent progress in the various lab-on-a-chip microtechnologies is reviewed and the clinical and research areas in which they have made the greatest impact are discussed. Lab-on-a-chip technologies in biomedical research and diagnostics Microfluidics exploits the properties of fluids trapped in submillimetre-scale spaces — the physics behind inkjet printing, DNA microarrays, lab-on-a-chip chemistry and much else — to useful practical effect. In the past decade microfluidic devices have shown considerable promise in diagnostics and primary research in the biological sciences. In this Review, Eric Sackmann, Anna Fulton and David Beebe analyse the progress seen in lab-on-a-chip microtechnologies in recent years and discuss the clinical and research areas in which they have made — and may make — the greatest impact. Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.