Toward a living soft microrobot through optogenetic locomotion control of Caenorhabditis elegans

Abstract

Learning from the locomotion of natural organisms is one of the most effective strategies for designing microrobots. However, the development of bioinspired microrobots is still challenging because of technical bottlenecks such as design and seamless integration of high-performance actuation mechanism and high-density energy source for untethered locomotion. Directly harnessing the activation energy and intelligence of living tissues in synthetic micromachines provides an alternative route to developing biohybrid microrobots. Here, we propose an approach to engineering the genetic and nervous systems of a nematode worm, Caenorhabditis elegans, and creating an untethered, highly controllable living soft microrobot (called “RoboWorm”). A living worm is engineered through optogenetic and biochemical methods to shut down the signal transmissions between its neuronal and muscular systems while its muscle cells still remain optically excitable. Through dynamic modeling and experimental verification of the worm crawling, we found that the phase difference between the worm body curvature and the muscular activation pattern generates the thrust force for crawling locomotion. By reproducing the phase difference via optogenetic excitation of the worm body muscles, we emulated the major worm crawling behaviors in a controllable manner. Furthermore, with real-time visual feedback of the worm crawling, we realized closed-loop regulation of the movement direction and destination of single worms. This technology may facilitate scientific studies on the biophysics and neural basis of crawling locomotion of C. elegans and other nematode species.

A high-throughput method to deliver targeted optogenetic stimulation to moving C. elegans populations

“…Patterned light from a projector, for example, can be used to illuminate only a subset of the cells expressing the optogenetic protein [24,25]. For targeting behaving animals, real-time processing is also needed to track the animal and dynamically update the illumination pattern based on its movements [26][27][28][29][30][31].…”

“…For example, delivering a perturbation triggered to the swing of an animal's head has informed our understanding of neural mechanisms underlying thermotaxis [32] and chemotaxis [8]. The use of closed-loop stimulation triggered on behavior in C. elegans [31,33], Drosophila [34], and mammals [35,36] is part of a broader trend in systems neuroscience toward more efficient exploration of the vast space of possible neural perturbations [37,38], especially during ethologically relevant naturalistic behaviors [39].…”

“…Targeted and closed-loop illumination systems probe one animal at a time [8,26,31,40,41] or, at most, 2 [42]. This low throughput poses challenges for acquiring datasets with enough statistical power to constrain quantitative models of neural computation.…”

Closed-loop targeted optogenetic stimulation of C. elegans populations

“…Patterned light from a projector, for example, can be used to illuminate only a subset of the cells expressing the optogenetic protein [25,26]. For targeting behaving animals, real-time processing is also needed to track the animal and dynamically update the illumination pattern based on its movements [27][28][29][30][31][32].…”

“…For example, delivering a perturbation triggered to the swing of an animal's head has informed our understanding of neural mechanisms underlying thermotaxis [33] and chemotaxis [9]. The use of closed-loop stimulation triggered on behavior in C. elegans [32,34], Drosophila [35] and mammals [36,37] is part of a broader trend in systems neuroscience towards more efficient exploration of the vast space of possible neural perturbations [38,39], especially during ethnologically relevant naturalistic behaviors [40].…”