We’ve seen robotic cars and humanoid assistants, but have you ever seen a robotic worm? On January 31, Professor Xinyu Liu from the Department of Mechanical and Industrial Engineering presented a talk at U of T’s Robotics Institute on the robotic manipulation and characterization of small model organisms. Professor Liu and his team study robotics as an “enabling technology for experimental studies of living biological samples such as cells, tissues, and organisms.” 

Nematodes in research: The star of the show

The star of Professor Lui’s recent research is a squiggly little worm called Caenorhabditis elegans (C. elegans), a nematode. 

Nematodes — a class of worms that feed on smaller micro-organisms — have been the model of success for several Nobel Prize winners in medicine and physiology in the past 25 years, including the 2024, 2006, and 2002 prizes. The reason for the ubiquity of C. elegans in biological research is its simplicity. 

It only has 302 neurons — the dominant cells in our nervous system — which have been completely mapped by researchers, making it a good choice for studying nerves, which function similarly in more complex organisms like ourselves. For reference, our own nervous system contains about 86 billion neurons. C. elegans are also used in genetic studies because it is easy to modify the worm’s genome — the entire set of genetic code found in a cell. Additionally, nematodes like C. elegans can be bred easily as they have short lifespans of about a month and thrive at room temperature. 

Professor Liu’s experimental innovations

However, conducting research with C. elegans also presents unique challenges, one of which involves injecting the worms with foreign material. In genetic studies, scientists modify an organism’s DNA by injecting new genes into the worm using a microneedle. The traditional process of manually injecting them is difficult and highly skill-dependent, with a 30 per cent success rate. 

Liu’s lab created a machine that uses microfluidics — technology that manipulates fluids flowing through minuscule channels — to funnel the worms one at a time to an injection site. The injection site is a narrow tube that squeezes the worm and immobilizes it. Once the worm is in the narrow tube, a camera-guided microneedle injects genetic material into the worm. This robotic implementation had a success rate of 80 per cent, which is much higher than manual injections. 

But Liu’s work doesn’t end there. His lab is also working to turn Nematode worms into ‘robots’ whose movements can be guided according to researcher instructions. This is done through optogenetics — a powerful technology that allows for fast, targeted, and precise control of different components of biological systems depending on their selective response to light. 

Neurons facilitate movement by electrically stimulating muscle cells. Liu and his team use optogenetics to control different neurons and what muscle cells they stimulate, which allows scientists the same control over model organisms such as C. elegans. Using optogenetic methods, genes that selectively respond to certain lights were inserted into an organism’s genome. As a result, whenever researchers shined a blue light on a muscle, for example, it would contract. 

Liu also needed to ensure the worm’s neurons were not independently causing the muscles to contract. To prevent this they used a chemical to temporarily disrupt the signal from the neuron to the muscle cells, paralyzing the worm. They could now use lights to control the motion of the worm by contracting different muscles, allowing them to manipulate it into navigating a maze, which is a significant step forward. 

The fact that worms can be directed by researchers to such a high degree of accuracy, highlights future possibilities where these worms can be used to push objects or soft electronics from one place to another. Sure, it is a little unsettling that scientists can control living worms with a flickering light, but in the name of science, isn’t it exciting?