An Automated Force-Controlled Robotic Micromanipulation System for Mechanotransduction Studies of Drosophila Larvae

摘要

The capability of accurately applying millinewton-level touch stimuli to Drosophila larvae and simultaneously observing their resultant fluorescence responses in mechanosensitive neuron transmission will enable novel studies of mechanotransduction neural circuitry. This paper presents an automated robotic micromanipulation system capable of force-controlled mechanical stimulation and quantitative fluorescence imaging of Drosophila larvae, which significantly improves the force regulation accuracy and operation consistency over conventional manual operations. An elastomeric microdevice is developed for efficient immobilization of an array of larvae for subsequent force-controlled touching. A microelectromechanical systems (MEMS) based force sensor is integrated into the robotic system for closed-loop force control of larva touching at a resolution of 50 μN. Two micromanipulators are coordinately servoed using orchestrated position and force control laws for automatic operations. The system performs simultaneous force-controlled larva touching and fluorescence imaging at a speed of four larvae per minute, with a success rate of 92.5%. This robotic system will greatly facilitate the dissection of mechanotransduction mechanisms of Drosophila larvae at both molecular and cellular levels.