Lab-on-a-chip: microfluidics in drug discovery

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 ex