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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.

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.

Great challenges still remain to develop drug carriers able to penetrate biological barriers (such as the dense mucus in cystic fibrosis) and for the treatment of bacteria residing in biofilms, embedded in mucus. Drug carrier systems such as nanoparticles (NPs) require proper surface chemistry and small size to ensure their permeability through the hydrogel-like systems. We have employed a microfluidic system to fabricate poly(lactic- co -glycolic acid) (PLGA) nanoparticles coated with a muco-penetrating stabilizer (Pluronic), with a tunable hydrodynamic diameter ranging from 40 nm to 160 nm. The size dependence was evaluated by varying different parameters during preparation, namely polymer concentration, stabilizer concentration, solvent nature, the width of the focus mixing channel, flow rate ratio and total flow rate. Furthermore, the influence of the length of the focus mixing channel on the size was evaluated in order to better understand the nucleation–growth mechanism. Surprisingly, the channel length was revealed to have no effect on particle size for the chosen settings. In addition, curcumin was loaded (EE% of ≈68%) very efficiently into the nanoparticles. Finally, the permeability of muco-penetrating PLGA NPs through pulmonary human mucus was assessed; small NPs with a diameter of less than 100 nm showed fast permeation, underlining the potential of microfluidics for such pharmaceutical applications.

A micromachined chemical amplifier was successfully used to perform the polymerase chain reaction (PCR) in continuous flow at high speed. The device is analogous to an electronic amplifier and relies on the movement of sample through thermostated temperature zones on a glass microchip. Input and output of material (DNA) is continuous, and amplification is independent of input concentration. A 20-cycle PCR amplification of a 176-base pair fragment from the DNA gyrase gene of Neisseria gonorrhoeae was performed at various flow rates, resulting in total reaction times of 90 seconds to 18.7 minutes.

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.

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.

Literature, newspapers or science use the internet, paper and written language for documenting their contents and transmitting it to the readers. The time scale for this is typically a human generation or can be much less. Technically speaking, printed paper, as such, will not necessarily survive very much longer. The computerized modern world has boosted the storage and accessibility of much more information. However, this has not improved the survival time scale [1]. [...]

Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

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.