A Better Way of Detecting Bacterial Toxins

An eighth-grade trip to the Jersey Shore has led Aravind Krishnan, C’25, W’25, to a promising new way of detecting toxins in medicine and drinking water. 

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During a school trip, Krishnan learned that the horseshoe crab population was threatened because they are harvested for the use of their blood to make a detection test for bacterial endotoxins. Horseshoe crabs have been around for more than 300 million years, and their blood still contains a type of immune cell called amebocytes. This type of cell is used to make an extract known as limulus amebocyte lysate (LAL), which detects the presence of toxins by clotting around them. LAL is used to ensure sterility of pharmaceuticals, vaccines (including the COVID-19 vaccines), and medical equipment and implants, and is vital to the lives of people around the world. In fact, almost every medical product you’ve ever used has likely been tested with the blood of the horseshoe crab.

The process of creating LAL makes it expensive, and while the companies that use horseshoe crabs for their blood try to do so sustainably, it is having an effect on the crab population. “Horseshoe crabs are one of the keystone species of the Jersey Shore ecosystem, which means that all the other species in the ecosystem rely upon them,” says Krishnan. “I learned from ecologists that the populations were declining because they were being harvested faster than they could be replenished by their own natural reproduction. So, loving nature and being curious about biology, I wanted to find out more.”

Krishnan spent much of that summer doing initial research, and was surprised to find there were no other detectors for bacterial toxins approved by the FDA. He was starting high school that fall, and made it one of his goals to try to develop an alternative: “I knew that was ambitious, of course, but I still wanted to make some progress towards solving this problem.”

His research pointed him at Arabidopsis, a member of a family of plants that includes cauliflower and cabbage. “This is one of the few families of plants that actually evolved to detect these bacterial toxins,” Krishnan says. He hypothesized that he could engineer Arabidopsis to serve as a natural sensor for bacterial toxins. He put together a research proposal and sent it to more than 100 professors in his area, including at universities like Rutgers and Princeton. Fewer than a dozen responded. “It's understandable from their perspective,” Krishnan says. “Not many ninth graders would come up to them and just pitch to them this new scientific research idea.”

He met with some of those who replied, and Eric Lam, a professor of plant biology at Rutgers, accepted Krishnan into his lab, giving him the space and resources to work on his project. By the end of high school, Krishnan had developed a bacterial toxin sensor system that he named ToxiSense.

When Krishnan was applying to colleges, Penn’s Roy and Diana Vagelos Program in Life Sciences and Management (LSM) seemed ideal. LSM students earn degrees in both a life science from the College of Arts & Sciences and in economics from Wharton. The goal is to produce graduates who can translate lab breakthroughs into medications and other useful products, and manage and promote those products. “I don't think there's any other program that combines this rigorous background in life sciences with business,” says Krishnan.

Once at Penn, Krishnan applied to the Spire Accelerator, a startup accelerator run by the Penn Social Entrepreneurship Movement (PennSEM). He met Udit Garg, ENG’25, who joined Krishnan to begin the ToxiSense team. They researched the regulatory hurdles they’d need to overcome to bring their product to market, general factors about the market, competitors, and other business aspects. 

Through other clubs, Krishnan and Garg met fellow first-year students Andrew Diep-Tran, W’25, and Aarush Sahni, C’25, and added them to the ToxiSense team. Diep-Tran already had business development experience, while Sahni would focus on scientific research and product development.

The four entered Venture Lab’s Startup Challenge, a competition for Penn student-founded ventures. They were competing against 30 other projects, most led by upperclassmen or graduate students. “We weren’t even expecting to make it to finals,” says Krishnan. When they did, they buckled down for the four days remaining. “The night before the competition we stayed up until 4:30 a.m. practicing our pitch,” he says. “We actually brought all of Udit’s hallmates to the lounge, and they were patiently listening and giving us feedback.”

The eight finals teams pitched to a panel of alumni judges in front of a live audience of nearly 200 attendees. ToxiSense came away with the Perlman Grand Prize, which includes $50,000 plus legal, accounting, and strategy services. 

This summer the team is focusing on increasing the sensitivity of the test and creating a synthetic version that will be more shelf-stable, and starting to prototype the test kit and conduct initial user testing. They’re also focusing on customer acquisition, including working with the Philadelphia Water Department with the help of the Penn Water Center. 

“The whole Penn community has been behind us,” Krishnan says. “From the professors and organizations that have supported us to our friends and hallmates—I think without them, none of this would've been possible, and we’re extremely grateful to them. I look forward to continuing to work with them as we continue our journey of turning that small spark of an idea five years ago into a new reality that is more sustainable and safe for both humans and ecosystems all around the world.”