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

Abstract

The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation. A moving wall design was integrated into this microfluidic platform first time in literature to accommodate zebrafish inside the microchannel from 1 day post-fertilization (dpf) to 6 dpf and can be further extended to 9 dpf for axial orientation control in a rotational range between 0 to 25 degrees at the minimum step of 2-degree increment in a stepwise manner. This moving wall feature was performed through the deflection of shape memory alloy wire embedded inside the microchannel controlled by the electrical waveforms with high accuracy.

Microfluidic Devices: A Tool for Nanoparticle Synthesis and Performance Evaluation

“…In addition to the geometry of the channel, alternative entrapping techniques are represented by the appliance of gravity force, , suction force, , and droplet encapsulation . Indeed, in order to improve the embryo handling and manipulation of zebrafish, a two-plate droplet-based “digital” microfluidic technology for on-chip transporting of zebrafish embryos was developed. , Additionally, on-chip high-quality imaging was developed to achieve fine-tuning of temperature, light, and oxygenated water levels, remote transport and orientation through light patterning, and dynamic culturing of zebrafish . This noninvasive automated system eliminated manual handling, enabling more accurate imaging measurements.…”

Microfluidic Applications of Artificial Cilia: Recent Progress, Demonstration, and Future Perspectives

“…Zebrafish have a similar genetic structure to humans, and researchers are interested in taking up zebrafish research to the next level by employing artificial cilia for zebrafish research. For instance, the artificial cilia were embedded in the microchannel which was facilitated with a moving wall feature using shape memory alloy to rotate and control the zebrafish stepwise for the benefit of hemodynamic screening [ 162 ]. The shape memory alloy-based miniaturized actuator’s detailed fabrication and the controlling process can be found elsewhere [ 163 ].…”

Comprehensive Hydrodynamic Investigation of Zebrafish Tail Beats in a Microfluidic Device with a Shape Memory Alloy

“…This manual practice is not only time-consuming but also incorporates significant substantial and morphological damage, which can lead to adverse zebrafish conditions, and it is not suitable for easy quantification of subtle behavioral responses, thus calling for alternative rapid and easy-to-use techniques [ 4 , 12 ]. To date, most of the zebrafish-screening- and imaging-associated studies relied heavily on skilled researchers with repetitive and generally manual zebrafish orientation control activity to image the region of interests [ 13 , 14 ]. The above shortcomings have inspired the development of microfluidics as an ideal form of miniaturization technology for the screening of the zebrafish with precision in order to provide significantly analytical efficiency and high-throughput effectiveness with no loss of accuracy and reliability in reduced expense, time, and energy expenditure [ 15 ].…”