Axial orientation control of zebrafish larvae using artificial cilia

Zebrafish has been used as an important vertebrate model of genetic screening and new drug development because of excellent characteristics, such as optical transparency, rapid ex vivo growth, and high genetic similarity to humans. Despite these advantages, studies on zebrafish are limited because of the lack of a robust and reliable method to manipulate zebrafish during microinjection and screening, as well as time-lapse imaging. In this work, a new microfluidic concept that utilizes a series of magnetically actuated artificial cilia integrated into a microchannel was employed to control the orientation of zebrafish larvae with a validated axial rotation capability. In contrast to conventional methods, the proposed method enables a highly accurate small-angle (0 degrees-20 degrees) stepwise axial rotation of a larva inside the microchannel with less detrimental effects on larval growth. The hemodynamics in a selected vessel was then imaged during the axial rotation of the tested larva to assist cardiovascular assessment. In addition, the bioactivity of the tested larvae remains stable without short-term negative effects after the imaging. The proposed platform, along with the provided analytical paradigm, can facilitate future zebrafish screening via microfluidics in the pharmaceutical industry.