Interactive manipulation of microparticles in an octagonal sonotweezer

Acoustic standing wave technology combined with microtechnology opens up new areas for the development of advanced particle and cell separating microfluidic systems. This tutorial review outlines the fundamental work performed on continuous flow acoustic standing wave separation of particles in macro scale systems. The transition to the microchip format is further surveyed, where both fabrication and design issues are discussed. The acoustic technology offers attractive features, such as reasonable throughput and ability to separate particles in a size domain of about tenths of micrometers to tens of micrometers. Examples of different particle separation modes enabled in microfluidic chips, utilizing standing wave technology, are described along a discussion of several potential applications in life science research and in the medical clinic. Chip integrated acoustic standing wave separation technology is still in its infancy and it can be anticipated that new laboratory standards very well may emerge from the current research.

We present an extracellular matrix (ECM) microarray platform for the culture of patterned cells atop combinatorial matrix mixtures. This platform enables the study of differentiation in response to a multitude of microenvironments in parallel. The fabrication process required only access to a standard robotic DNA spotter, off-the-shelf materials and 1,000 times less protein than conventional means of investigating cell-ECM interactions. To demonstrate its utility, we applied this platform to study the effects of 32 different combinations of five extracellular matrix molecules (collagen I, collagen III, collagen IV, laminin and fibronectin) on cellular differentiation in two contexts: maintenance of primary rat hepatocyte phenotype indicated by intracellular albumin staining and differentiation of mouse embryonic stem (ES) cells toward an early hepatic fate, indicated by expression of a beta-galactosidase reporter fused to the fetal liver-specific gene, Ankrd17 (also known as gtar). Using this technique, we identified combinations of ECM that synergistically impacted both hepatocyte function and ES cell differentiation. This versatile technique can be easily adapted to other applications, as it is amenable to studying almost any insoluble microenvironmental cue in a combinatorial fashion and is compatible with several cell types.