Assistant professor Bozhi Tian, recently the recipient of an NIH New Innovator Award and a Presidential Early Career Award for Scientists and Engineers, has been dreaming about combining humans with electronics since his days as a graduate student in physical chemistry at Harvard. With a background in building nanoscale electronic devices and cellular engineering, Tian’s latest discovery brings him a step closer to creating cyborg cells—moving beyond mere prosthetics to devices that can respond to light or stimulate muscle contractions. Though modest about the revolutionary potential of his work for biomedical use, Tian’s energy and enthusiasm for his work is palpable.
Tian explains that all his work is driven by the pursuit of fundamental questions. “We were thinking of the molecular level structure and the mechanics of the device, which allows for its seamless integration with cellular components,” he says, introducing his wireless electrical stimulator, a spongy, deformable silicon developed in his lab. While stiff materials prompt bodies to respond to the irritation with inflammation, soft materials move with the body’s own tissue, limiting damage—and, as he puts it, “biological materials . . . like them.”
While most researchers have placed their focus on soft polymers for tissue repair, Tian and his lab have concentrated on silicon, a traditionally hard material. “It has unique physical properties,” he says, referring to its ability to interact with light and generate electrical impulses. “Because silicon is usually rigid, we wanted to discover a material as mechanically deformable as polymers that retains most of silicon’s special properties. The conductivity of traditional silicon is somewhere between an insulator, like glass, and a metal, like gold. Because it’s in-between, you have a lot of room to tune it, and if you can regulate it, the device becomes active and even multifunctional. For example, the output voltage from a silicon-based device can be modulated by changing the input voltage, which results in a kind of circuit. One nice thing about an active device is that you can also amplify a tiny amount of input signal into a big output.”
A year ago, his lab succeeded in producing just such a material. Porous in nature, it combines deformability, biocompatibility, and biodegradability with the possibility of making devices that respond to light by generating heat and eventually electricity directly across a biological membrane—in other words, an ideal material with potential for repairing or replacing nerve tissue. “We found that when we shone light onto a spongy silicon surface which attached to a cell membrane, the silicon could convert energy from the incident light into something like electrical stimulation,” Tian says. “We’re using light to modulate neural activity using spongy silicon as a transducer. One promising application is repairing photoreceptors in damaged retinas.”
Another possible application the Tian lab is exploring is repairing peripheral nerve damage. “We could inject the spongy silicon into skeletal muscle and shine light on it. The silicon then stimulates the muscle like the original nerve,” he explains. “Alternatively, we can combine a silicon-based network with a collagen-based conduit to promote nerve regeneration.”
Tian and his group are in the early phases of their biomedical studies, moving from calibration of their material in vitro to in vivo studies in, for instance, blind mice. “We want to show the field that our material can have a good impact,” he says. He also notes that his interest in exploring biomedical applications of their material emerges as an extension from their fundamental studies: “If we don’t do it, no one will.”
However, the majority of Tian’s research is aimed at understanding the electrical behavior of biological systems, such as how cytoskeleton and motor proteinsrespond to localized electrical stimulation. “In the past, there were no tools to understand such processes from an electrical perspective,” Tian says. Most of the information we have is superficial: for example, we have a plate of cells and near it we place some electrodes and see how the cells migrate. But we are trying to understand how it works on a molecular level.”
On such a scale, direct measurement remains a significant challenge. “If we place a global electrode, everything becomes messy, and you can’t see anything because you target the entire cell.” But Tian has developed a way to observe the effects of electrical stimulation on cytoskeletal filaments within insect cells. “We designed a nanoscale solar cell and let the cell internalize the solar cell. Essentially, it is a wireless electrical stimulation device that can be placed inside the cell and targeted to a specific component. When we shine light, the tiny solar cell responds and generates a transient electrical output from the interior of the cell. Then we watch how the cell responses changes from this electrical perturbation.” This set of experiments is critical for understanding how the increasing use of implantable electronic devices may affect humans on a cellular or subcellular level.
“For me, the exploration of a new frontier or the discovery of a new phenomenon is the most important thing. I like unexpected things and unconventional paths. I would not put application (at least at this career stage) as the major driving force of my research. There are a lot of mysteries, and we are trying to understand only one part.” Furthermore, Tian admits, bioelectrics, the study of electrical behavior or phenomena in biological systems, is an open field with few players at present. “I don’t want to work in a crowded field. If you work in a crowded area, even if it’s a hot area, it’s unlikely to be the first person to discover something. You feel nervous, and you always ask yourself, ‘What if my work is scooped by someone else?’ and you put that pressure on your students—and you will not sleep well. And then I would not enjoy science! I like to work on things that may become important only in 5 years, 10 years or even longer—that is how we can become real leaders. If we understand the origin of bioelectrics, we can understand a lot of things that have been mysteries for centuries, such as deep brain stimulation and acupuncture—we know that they work, but why?”
(Irene Hsiao, The Chemists Club, Autumn 2016)