Fish-on-a-chip: microfluidics for zebrafish research

High-efficiency zebrafish (embryo) handling platforms are crucially needed to facilitate the deciphering of the increasingly expanding vertebrate-organism model values. However, the manipulation platforms for zebrafish are scarce and rely mainly on the conventional static microtiter plates or glass slides with rigid gel, which limits the dynamic, three-dimensional (3D), tissue/organ-oriented information acquisition from the intact larva with normal developmental dynamics. In addition, these routine platforms are not amenable to high-throughput handling of such swimming multicellular biological entities at the single-organism level and incapable of precisely controlling the growth microenvironment by delivering stimuli in a well-defined spatiotemporal fashion. Recently, microfluidics has been developed to address these technical challenges via tailor-engineered microscale structures or structured arrays, which integrate with or interface to functional components (e.g. imaging systems), allowing quantitative readouts of small objects (zebrafish larvae and embryos) under normal physiological conditions. Here, we critically review the recent progress on zebrafish manipulation, imaging and phenotype readouts of external stimuli using these microfluidic tools and discuss the challenges that confront these promising fish-on-a-chip technologies. We also provide an outlook on future potential trends in this field by combining with bionanoprobes and biosensors.