Mechanosensation is required for multiple sensory modalities such as touch, hearing, and balance, and is linked to a multitude of disorders including deafness. Molecular mechanisms for mechanotransduction have been partially elucidated using a variety of model organisms, including
Caenorhabditis elegans. Conventional mechanosensation experiments with
C. elegans typically involve the manual delivery of a mechanical stimulus via an eyebrow hair or metal pick, and visual scoring of touch avoidance behavior, an assay subject to considerable variability between experimenters. Microfluidics has long been used for well-controlled and high-throughput experiments with small samples. In addition to enabling precise perturbations on the micron scale, microfluidic devices can easily be designed to work together with optical microscopy, allowing for imaging of fluorescent probes such as calcium indicators. For
C. elegans experimentation particularly, microfluidics has been a widely adopted technology due to the match in length scale and compatibility with fluid handling. In this talk, I will present a microfluidic platform for delivering robust and precise mechanical stimuli to
C. elegans by using
pneumatically actuated structures. The device is fully automated, minimizing human variability and improving experimental throughput; it is fully compatible with fluorescent imaging of calcium dynamics of neurons. We show that this device can deliver mechanical stimuli with precise control in timing, location, and deformation. These characteristics allow us not only to recapitulate the well-known receptive field of the neurons in the gentle-touch circuit, but also to understand the dynamics of the harsh-touch neurons. We further developed this microfluidic system to interrogate behavior of mechanosensory neurons during development. Another direct application of the devices are in drug screens in a humanized worm model. Our microfluidic system directly addresses the current bottleneck of a lack of functional assay for such drug screens. The ability to automate and streamline the microfluidic system will greatly enhance our ability to identify potential therapeutics.
