Of mice and (wo)men: Engineering tool to assist in the study of the brain

Siyuan Rao, an assistant professor of biomedical engineering, would have been a great addition to campus all on her own — but bringing along five doctoral students, her entire lab and the projects they’re working on makes this move a special one.

“We have the entire graduate student team moving with me,” Rao said. “And we actually have a very ambitious research goal, from fundamental neurobiology material science all the way to the translational applications. We have patents under review and more new innovations on the way. We hope to create real new products that focus on spinal cord injury or brain recordings.”

Rao has recently completed a move from her lab’s previous iteration, located at the University of Massachusetts Amherst, and is settling into her new position at Binghamton University’s Thomas J. Watson College of Engineering and Applied Science. She is one of 36 new staff members who were welcomed to campus through a $6.5 million initiative directly from the SUNY system.

New approaches to neurology

To understand the mechanisms that keep our brains functioning and develop effective treatments to help when things go wrong, Rao’s research links behavior and cellular activity. Using implantable soft material bioelectronic devices and a magnetic toolkit, her research team hopes to create better ways to understand the brain, and potentially develop therapeutic approaches for neurological disorders.

“We are providing engineering and new approaches to tackle neurobiological questions while trying to bridge the understanding of those mechanisms all the way to treatment,” said Rao, who received her doctorate in materials physics and chemistry at Beihang University and began her postdoctoral research in neuro-engineering and bioelectronics at the Massachusetts Institute of Technology in 2016.

While at MIT, she co-invented with her colleagues a specialized technique known as “the chemomagnetic technique.” It combines the magnetic toolkit she uses in her research with behavioral neuroscience practices to enable precise corrections to the neural circuitry that affects motivation and social interaction.

Rao launched her Neurobiological Interfaces Lab in 2021, and like her postdoctoral work, it is highly interdisciplinary. Her team sits at the intersection of materials science engineering, electrical engineering, neuroscience and biomedicine. Her work can be complex and multifaceted, and her doctoral students can come from a variety of backgrounds — yet they all benefit from a unique model of mentorship.

“Each PhD student is building their own team by independently recruiting undergraduate students. They have relatively independent projects,” Rao said. “I want to train my students as leaders, in our current lab and also in the future. I want them to leave with a comprehensive expertise in the field and also help in building their own career.”

The teams are working on topics that fall under the greater umbrella of Rao’s work. The fundamental building blocks — implantable soft material bioelectronic devices into the nervous system and magnetic devices to impart non-invasive stimulus — serve as a starting point for the student’s interests in their unique fields. The students have made significant process in both parts of the project.

Inhibiting pain through implants

In October 2023, Rao and her students published a paper in the journal Nature Methods titled “Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion,” which introduced the hydrogel soft fiber devices to inhibit pain in mice models. Rao’s devices are made of a new type of fatigue-resistant hydrogel, which is able to adapt to the tissue motion when the experimental subjects are moving, and optogenetically transmit light to the neurons, delivering treatments while a patient is cognizant.

“This device can be very soft, transparent and stretchable. If you’ve implanted in the experimental subject, even if this animal is running around having very fierce moving behaviors, that material can adapt to that tissue movement without causing local damage,” Rao said. “Two months after implantation, this device is still effective in inhibiting thermal pain and mechanical pain.”

Studying behaviors in a natural setting can greatly affect the results that you receive, she added. Once you change a behavior, you are potentially looking at the “constrained self”: an altered behavior because of the subject’s inhibited nature. This type of soft bioelectronics opens up access to study the neural mechanism when the experimental subjects are naturally behaving.

Rao hopes that the research can be compiled and used to improve the ways that our brains and bodies are studied. She would one day like to be able to mass-produce the hydrogel fiber probes used in her lab in a fashion similar to the battery hub recently added to campus. For now, she is committed to helping recruit more women into STEM-related fields and to continue her research so the devices can be used for a variety of applications.

“Our goal is to integrate multiple functionalities within the same device. Right now, we achieved the first step, transmitting light,” Rao said. “The next step we are trying is to put an electrode here to record the electrical signal and even infuse drug or genetic viral vectors to enable gene therapy. Ultimately, we want to create a comprehensive but still miniaturized device that can do everything all in one.”