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Responding to the need for an affordable, easy-to-read textbook that introduces microfluidics to undergraduate and postgraduate students, this concise book will provide a broad overview of the important theoretical and practical aspects of microfluidics and lab-on-a-chip, as well as its applications.

Key Points Miniaturization from conventional to small size results in several advantages, such as reduced sample consumption and shortened transport times of mass and heat. A key feature in microfluidic systems is the integration of different functional units for reaction, separation and detection in a channel network. Therefore, serial processing and analysis could be easily performed in the flowing systems. Furthermore, because space is used sparingly, massive parallelization can be accomplished. In microfluidic chips, chemical syntheses can be performed. Concentration of reagents and temperature can be regulated precisely. Operating under continuous flow conditions will also allow the combination of multiple reaction steps and on-line analysis on one single chip. Serial and parallel solution-phase synthesis is demonstrated in microchips. Microfluidic screening and sorting devices have been developed that offer the benefits of a continuous operation, including reaction steps preceding as well as succeeding the sorting process. In combination with appropriate biological assays and high-sensitivity detection techniques, such systems allows the identification and isolation of individual cells or molecules. Microfluidic chips facilitate the generation and handling of nano- and picolitre liquid volumes. By injecting the aqueous phase into the stream of the carrier medium at a T-junction or by applying focussing techniques, small reaction chambers ('droplets') are generated. The precisely controllable supply of reagents, handling of small liquid volumes devoid of fast evaporation as well as the high-speed formation of droplets with a homogeneous diameter of a few μm makes this approach a valuable tool for screening experiments that rely on high reproducibility. By generating technologies with nanoscale dimensions, reaction volumes are being achieved similar to those typically found in biological systems such as living cells. Recent studies show the possibility of using microfluidic platforms for cell culturing and observation and being able to manipulate living cells individually. Using microfluidics, cells could be locally stimulated, for example, to study the effect of drug levels on chemotaxis of living cells in vitro . In key issues of drug discovery, such as chemical synthesis, screening of compounds and preclinical testing of drugs on living cells, microfluidic tools can meet the demands for high throughput, and can improve or might eventually replace existing technologies. Advances in microfluidics could prove invaluable both by enhancing existing biological assays and for the design of sophisticated new screens. Dittrich and Manz review current and future applications of scaled-down science and look at the impact of lab-on-a-chip technology on drug discovery. Miniaturization can expand the capability of existing bioassays, separation technologies and chemical synthesis techniques. Although a reduction in size to the micrometre scale will usually not change the nature of molecular reactions, laws of scale for surface per volume, molecular diffusion and heat transport enable dramatic increases in throughput. Besides the many microwell-plate- or bead-based methods, microfluidic chips have been widely used to provide small volumes and fluid connections and could eventually outperform conventionally used robotic fluid handling. Moreover, completely novel applications without a macroscopic equivalent have recently been developed. This article reviews current and future applications of microfluidics and highlights the potential of 'lab-on-a-chip' technology for drug discovery.

Sinusoidal endothelial cells and mesenchymal CXCL12-abundant reticular cells are principal bone marrow stromal components, which critically modulate haematopoiesis at various levels, including haematopoietic stem cell maintenance. These stromal subsets are thought to be scarce and function via highly specific interactions in anatomically confined niches. Yet, knowledge on their abundance, global distribution and spatial associations remains limited. Using three-dimensional quantitative microscopy we show that sinusoidal endothelial and mesenchymal reticular subsets are remarkably more abundant than estimated by conventional flow cytometry. Moreover, both cell types assemble in topologically complex networks, associate to extracellular matrix and pervade marrow tissues. Through spatial statistical methods we challenge previous models and demonstrate that even in the absence of major specific interaction forces, virtually all tissue-resident cells are invariably in physical contact with, or close proximity to, mesenchymal reticular and sinusoidal endothelial cells. We further show that basic structural features of these stromal components are preserved during ageing. The bone marrow microenvironment modulates haematopoiesis, stem cell maintenance and differentiation. Here, the authors use 3D microscopy to map the topography of haematopoietic stem cell niche stromal components.

▪ Abstract  In vertebrates, serum antibodies are an essential component of innate and adaptive immunity and immunological memory. They also can contribute significantly to immunopathology. Their composition is the result of tightly regulated differentiation of B lymphocytes into antibody-secreting plasma blasts and plasma cells. The survival of antibody-secreting cells determines their contribution to the immune response in which they were generated and to long-lasting immunity, as provided by stable serum antibody levels. Short-lived plasma blasts and/or plasma cells secrete antibodies for a reactive immune response. Short-lived plasma blasts can become long-lived plasma cells, probably by competition with preexisting plasma cells for occupation of a limited number of survival niches in the body, in a process not yet fully understood. Limitation of the number of long-lived plasma cells allows the immune system to maintain a stable humoral immunological memory over long periods, to react to new pathogenic challenges, and to adapt the humoral memory in response to these antigens.

Micrometre-scale analytical devices are more attractive than their macroscale counterparts for various reasons. For example, they use smaller volumes of reagents and are therefore cheaper, quicker and less hazardous to use, and more environmentally appealing. Scaling laws compare the relative performance of a system as the dimensions of the system change, and can predict the operational success of miniaturized chemical separation, reaction and detection devices before they are fabricated. Some devices designed using basic principles of scaling are now commercially available, and opportunities for miniaturizing new and challenging analytical systems continue to arise.

Background The interactions between unemployment and mental health are complex. However, broad and current epidemiological data about the mental health status of unemployed individuals in Germany are scarce. This study aimed to evaluate the prevalence rates of mental disorders and work ability among all unemployed people who underwent socio-medical assessment by the Federal Employment Agency (FEA). Methods Socio-medical assessments between 2016 and 2021 were taken from the FEA database and analyzed regarding sociodemographic characteristics, mental disorders and work ability. Standard descriptive statistics were used to analyze the data. Results A total of 4,249,028 unemployed individuals were assessed. Of these, 2,213,048 persons (52.1%) had at least one psychiatric diagnosis (mean age 40.6 ± 13.5 years, 51.7% female). Mood disorders (53.9%), neurotic, stress-related and somatoform disorders (43.9%), as well as substance use disorders (15.3%) showed the highest prevalence rates among mental disorders and accounted for about 80% of all psychiatric diagnoses. About 40% of them were evaluated to be able to work full time. Conclusions Psychiatric morbidity among unemployed people is high. However, a significant proportion of them was assessed to be able to return to the labor market. Therefore, close collaborations between unemployment agencies and mental health care institutions as well as specific re-integration programs including supported job placement and vocational training, long-term job coaching as well as integrated mental health care are required in order to improve mental health status, prevent further chronification, avoid labor market exit, and increase employment rate.

Immune protection is based on long-lived memory cells and effector cells, which are either cytotoxic or secrete antibodies. The lifespan of these effector cells has not so far been determined. Here we show that antibody-secreting plasma cells from bone marrow are as long-lived as memory B cells.

In recent years, the development of polymerase chain reaction (PCR) technology has focused on digital PCR, which depends on the microfluidics. Based on continuous-flow microfluidic technology, this paper designed a miniaturized digital PCR amplification system, and greatly reduced the area required for microdroplet generation and reaction. The core rod. made of polydimethylsiloxane (PDMS), was combined with the Teflon tube to form 3D microfluidics, which requires only one heating source to form the temperature difference required for gene amplification. Only two 34 g needles can form and transmit micro-droplets in a 4-fold tapered Teflon tube, which is the simplest method to generate digital PCR droplets as far as we know, which allows the microdroplet generation device to be free from dependence on expensive chips. A complementary metal oxide semiconductor (CMOS) camera was used as a detection tool to obtain fluorescence video for the entire loop area or a specified loop area. In addition, we developed a homebrew for automatic image acquisition and processing to realize the function of digital PCR. This technique realizes the analysis of clinical serum samples of hepatitis B virus (HBV) and obtained the same results as real-time quantitative PCR. This system has greatly reduced the size and cost of the entire system, while maintaining a stable response.

Key Points Recent progress in lab-on-a-chip (LOC) technology and microfluidics is reviewed in this article, with a special focus on drug discovery. We introduce relevant scaling laws, together with the means by which the use of LOC technology could be advantageous. We discuss the origin of microfluidics and its benefits compare to conventional approaches. We discuss microfluidic techniques such as droplet microfluidics and patch clamp techniques, as well as their applications in drug discovery The applications of microfluidic techniques include measurements of enzyme activity and kinetics, drug–protein interactions, DNA synthesis and protein expression. Microfluidics can also be used for three-dimensional cell culturing, the development of organs-on-a-chip, as well as for the analysis of animals-on-a chip. Manz and colleagues discuss recent progress in the development of microfluidic techniques (lab-on-a-chip technology) and their applications in drug discovery. Highlights include high-throughput droplet technology and applications such as 'organs on a chip', which could help reduce reliance on animal testing. The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.