AbstractThe nematodeCaenorhabditis elegansis one of the most widely studied organisms in biology due to its small size, rapid life cycle, and manipulable genetics. Research withC. elegansdepends on labor-intensive and time-consuming manual procedures, imposing a major bottleneck for many studies, especially for those involving large numbers of animals. Here, we describe a general-purpose tool, WormPicker, a robotic system capable of performing complex genetic manipulations and other tasks by imaging, phenotyping, and transferringC. eleganson standard agar media. Our system uses a motorized stage to move an imaging system and a robotic arm over an array of agar plates. Machine vision tools identify animals and assay developmental stage, morphology, sex, expression of fluorescent reporters, and other phenotypes. Based on the results of these assays, the robotic arm selectively transfers individual animals using an electrically self-sterilized wire loop, with the aid of machine vision and electrical capacitance sensing. AutomatedC. elegansmanipulation shows reliability and throughput comparable with standard manual methods. We developed software to enable the system to autonomously carry out complex protocols. To validate the effectiveness and versatility of our methods, we used the system to perform a collection of commonC. elegansprocedures, including genetic crossing, genetic mapping, and genomic integration of a transgene. Our robotic system will accelerateC. elegansresearch and open possibilities for performing genetic and pharmacological screens that would be impractical using manual methods.