Robotic Stimulation of Freely Moving <italic>Drosophila</italic> Larvae Using a 3D-Printed Micro Force Sensor

Abstract

The Drosophila larva is an excellent model organism in biology for studying the mechanisms of sensory mechanotransduction and the neural basis of behavior. This paper reports an automated robotic micromanipulation system capable of force-controlled mechanical stimulation and locomotion behavior analysis of freely moving Drosophila larvae, which improves the force regulation accuracy and larva operation consistency over conventional manual manipulation. A three-dimensionally-printed, three-axis micro force sensor was developed and integrated into the robotic system to measure the contact force between the tip of an end-effector and the larva head, and an adaptive fuzzy proportional-integral-derivative (PID) controller was proposed for closed-loop control of the contact force. The three-axis force sensor was also employed to monitor lateral disturbances to the contact force caused by small larva head movements, and thus validate the effectiveness of larva stimulation. The robotic system performed automated larva stimulation and locomotion analysis at a speed of four larvae per minute, and was applied to quantify the correlation between the applied contact force direction/magnitude and the larva reorientation behavior. With its high accuracy and efficiency, this system will greatly facilitate large-scale studies of mechanosensory behaviors in Drosophila larva.