Micro total analysis systems for cell biology and biochemical assays.

Novel applications of micro total analysis systems (µTAS) are addressing fundamental biological questions, creating new biomedical reagents, and developing innovative cell and biochemical assays. These efforts impact progress in all areas of µTAS from materials to fluidic handling as well as detection and external control systems. Three areas show the greatest current and potential impact on the biomedical sciences: improvements in device fabrication and operation, development of enabling technologies, and advancements at the interface with biology (Figure 1). The range of materials from which devices can be fabricated has expanded considerably and now includes paper, fabric and thread, and a multitude of polymers as well as more conventional materials. Thus device substrates and component materials suitable for nearly all biological applications are readily available. Devices are also becoming increasingly integrated with advancements in sample handling and preparation, key first steps in any biological analysis. Another growing area focuses on modular components that can be mixed and matched on-demand and applied to many different assays, so-called programmable microfluidics. This development should enhance the rate at which new bioassays are generated as well as customize existing experimental protocols. A second area of rapid advancement has been the development new technologies that enable assays that cannot be efficiently performed by any method except µTAS. Novel analyses of single cells are enabled due to effective manipulation of picoliter-scale volumes. Synthesis and screening of large-scale libraries has become increasingly feasible due to the fast processing speeds and combinatorial mixing of reagents provided by lab-on-chip systems. Increased automation within a completely contained system has now begun to provide some of the first true µTAS diagnostic devices for clinical medicine. The third area in which µTAS has begun to yield high dividends is the interfacing of living entities with microdevices to create biological communities, including tissues and organs on-chip. Control of cell placement in multiple dimensions has produced biological systems midway between the conventional tissue-culture dish and an intact animal. Thus the complexities of living constructs can be recreated in a controlled experimental environment permitting groundbreaking biological questions to be addressed. Application of µTAS in all of these areas continues to be highly interdisciplinary, utilizing techniques and strategies from almost every scientific field. This multidisciplinary focus insures continued relevance to the biological community as well as a bright future. Figure 1 We highlight recent contributions to µTAS in three interlocking areas: fabrication & operation, enabling technologies, and interfacing with biology. Due to the rapid progress of µTAS or “lab-on-a-chip” systems, this review focuses on advances impacting cell biology and biochemistry and covers the time span from March 2010 through August 2011. The material for the review was compiled using several strategies: reviews of high impact journals such as Analytical Chemistry, Lab on a Chip, Science, Nature, and PNAS; extensive key word searches in databases such as PubMed, SciFinder, Web of Science, and Google Scholar; and screens of other recent topical reviews. Although several thousand papers were identified and over a thousand papers received a detailed examination, we focused on the most novel and exciting methods, devices, and applications in the areas of cell biology and biochemistry. We also endeavored to cover the most prominent work from a range of labs and countries. Ultimately we were limited by space constraints and our desire to craft a readable commentary on the state of the field. We apologize in advance for omitted papers and welcome feedback regarding any oversights on our part.