High-Throughput Controlled Mechanical Stimulation and Functional Imaging In Vivo

Abstract

Understanding mechanosensation and other sensory behavior in genetic model systems such as C. elegans is relevant to many human diseases. These studies conventionally require immobilization by glue and manual delivery of stimuli, leading to low experimental throughput and high variability. Here we present a microfluidic platform that delivers precise mechanical stimuli robustly. The system can be easily used in conjunction with functional imaging and optical interrogation techniques, as well as other capabilities such as sorting or more sophisticated fluid delivery schemes. The platform is fully automated, thereby greatly enhancing the throughput and robustness of experiments. We show that behavior of the well-known gentle and harsh touch neurons and their receptive fields can be recapitulated in our system. Using calcium dynamics as a readout, we demonstrate the ability to perform a drug screen in vivo. Furthermore, using an integrated chip platform that can deliver both mechanical and chemical stimuli, we examine sensory integration in interneurons in response to multimodal sensory inputs. We envision that this system will be able to greatly accelerate the discovery of genes and molecules involved in mechanosensation and multimodal sensory behavior, as well as the discovery of therapeutics for related diseases.