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

Abstract

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.

Manipulation of zebrafish’s orientation using artificial cilia in a microchannel with actively adaptive wall design

“…The aforementioned statement can be verified in a recent manuscript17 where the authors have reviewed zebrafish manipulation platforms available till date and listed specifications of each devices. Our proposed microfluidic platform with a moving wall function will be able to advent the zebrafish entrapping technologies in terms of accommodating the vertebrae model throughout their embryonic developmental stages.…”

Single-cell in vivo imaging reveals light-initiated circadian oscillators in zebrafish

“…With advanced microfluidic systems to capture and recapture larval zebrafish, one can conduct more intense imaging on the same fish to achieve higher temporal resolution while minimizing the perturbations to the fish [28]. Using newly developed movable platform to track zebrafish larvae and novel volume imaging system, live imaging of cellular circadian rhythm on free-moving zebrafish will become possible [29].…”

Microfluidics for mechanobiology of model organisms

“…Most microfluidic devices for zebrafish have focused on trapping embryos or larvae for long-term imaging (reviewed by Yang et al (2016)). The biggest challenges in the design of a zebrafish microfluidic-based chip compared to other model organisms are (1) the zebrafish is a freshwater organism and needs sufficient perfusion for fresh water exchange to deliver oxygen and maintain consistent pH without damaging the animal, and (2) embryos develop at an optimal temperature of 28–29°C (Westerfield, 2000), so a heating system may be necessary for the health of the fish.…”