LAB-ON CHIP

Standard cell culture techniques have remained basically unchanged for almost a century. Over the past decade the convergence of micro and nanoengineering with microfluidics and cell biology is leading to the development of a new approach to biological studies aimed to recreate organs and complex biological processes on chip in a more physiologically relevant context. The exploitation of Lab-on Chip have pervaded various fields to address the formidable pharmacological and physiological gaps between monolayer cell cultures, animal models, and humans that severely limit the speed and efficiency of drug development.

Traditional disease models provide only limited diagnostic information because they generally analyze the drug response of isolated cells in an artificial environment is the only way to obtain in vivo pharmacokinetic and pharmacodynamic response data. However, this approach is currently one of the major bottlenecks with high costs (more than $2m), lengthy testing duration and often fail to predict reliably human toxicity or efficacy physiological responses due to metabolic and physiological differences. In addition, this is subject to various ethical constraints. Accordingly, microfluidic devices may serve to bypass or mimic animal testing by re-creating tissues using co-culture of multiple cell types. Microsystems provide new cell culture microenvironments to manage complex experiments to analyze cell populations or even single cells, allowing for quantitative and real-time measurements. Soluble biochemical factors, extracellular matrix interactions, homotypic and heterotypic cell-cell signaling, physical cues (e.g. oxygen tension, pH, temperature), and mechanical forces (e.g. shear, topography, rigidity) can be finely tuned. Microfluidic liquid handling allow to integrate, automate, parallelize and miniaturize assay formats with increased throughput and measurement reproducibility. Recent research efforts have made it possible to recapitulate tissue-tissue interfaces and the complex 3D microarchitectures of specific organs integrating crucial dynamic mechanical cues as well as spatiotemporal chemical signals.

Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, have created one of the most sophisticated devices so far: a “lung-on-a-chip” by mimicking the alveolar capillary interface including mechanical actuation of the interface into the model. The great challenge lies in the ability to integrate functional organ mimetics. The US Department of Defense’s Defense Advanced Research Projects Agency is now supporting a project up to $37 million aiming to link ten or more functional organs together such as gut-, liver-, lung- and skin-on-chips within a ‘human-on a-chip’ as a unique, integrated, chip-based multi-organ screening paradigm. Microengineered organ-on-chip may provide novel platform more predictive of drug efficacy and toxicity in patients . These have been nicknamed 'Homo chippiens' by some working in the field.

Labs on chip devices provide an interactive environment to foster multidisciplinary approaches to take problems at the interface Biology, Chemistry and Physics. Collaborative efforts between researchers with distinct state of the art and expertise will be necessary by means of a synergetic approach to create tools that can be translated from lab innovations to high-impact products in pharmaceutical industry.