Microfluidic Devices for Behavioral Screening of Multiple Zebrafish
Larvae: Design Investigation Process
Abstract
Microfluidic devices have been introduced for phenotypic screening of
zebrafish larvae in both fundamental and pre-clinical research. One of
the remaining challenges for the broad use of microfluidic devices is
their limited throughput, especially in behavioural assays. Previously,
we introduced the tail locomotion of a semi-mobile zebrafish larva
evoked on-demand with electric signal in a microfluidic device. Here, we
report the lessons learned for increasing the number of specimens from
one to four larvae in this device. Multiple parameters including loading
and testing time per fish and loading and orientation efficiencies were
refined to optimize the performance of modified designs. Simulations of
the flow and electric field within the final device provided insight
into the flow behavior and functionality of traps when compared to
previous single-larva devices. Outcomes led to a new design which
decreased the testing time per larva by approximately 60%. Further,
loading and orientation efficiencies increased by more than 80%.
Critical behavioural parameters such as response duration and tail beat
frequency were similar in both single and quadruple-fish devices. The
optimized microfluidic device has significant advantages for greater
throughput and efficiency when behavioral phenotyping is required in
various applications, including chemical testing in toxicology and gene
screening.