Engineering a Solution to Cancer

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Over the course of his career as a mechanical engineer, Greg Sawyer relished working on what he thought were “the hardest problems” in engineering — controlling surfaces to make things work in challenging environments, such as space.

He cut his teeth at NASA’s Jet Propulsion Laboratory in the early 1990s, working with a small design team on what would eventually become the first Mars Rover. Later, as a faculty member at the University of Florida, he ran a surface engineering lab and led an effort to develope low-friction nanocomposite materials — including a “super Teflon” of sorts — to make it easier for spacecraft components to move and slide but still be able to withstand radiation, extreme temperatures and other hazards in space. He also trained students, developed instruments and collaborated with scientists across the globe on methods of engineering surfaces to help things slide, move, support loads and conduct electricity.

That all changed in 2013, when Sawyer was diagnosed with Stage IV melanoma, a deadly skin cancer that had spread to his spine.

The days that followed were filled with scans, tests and surgeries. The doctors told him he’d probably had the cancer for years without knowing it, and they gave him a “very short horizon,” he says. The worst moment was telling his two sons, who were then 7 and 12 years old, that he had cancer, and when he eventually returned to his lab, he broke down in tears, wondering how he’d tell his students that he likely wouldn’t see them graduate.

Sawyer decided he’d help them wrap up the projects they were working on but was hesitant to take on any new students or new projects. He also decided that when he was gone, he’d leave as much of his lab as he could to cancer research.

Fortunately for Sawyer, immunotherapy he received in a clinical trial saved his life. Seizing the opportunity, he set out to determine how the tools he’d developed over his two-decade career could actually be helpful to cancer researchers.

He threw himself into immunology textbooks and the journal Nature and started sitting in on meetings at the College of Medicine where physicians were discussing clinical cases. Much of the time, he felt like he was trying to understand a foreign language, and he found it all personally exhausting. “I spent two years feeling guilty that I had this time, which was precious, but I was unable to find a way to help the biologists do what they were doing better, and I felt very guilty for not being smart enough to be a good enough biologist to be able to help them,” he recalls.

He didn’t turn the corner, he says, until he stopped trying to think like a biologist and went back to thinking like an engineer. Engineers, Sawyer says, approach whatever problem they’re working on by “putting it in the middle” and positioning their tools around the perimeter. Once he did that, it became obvious what was missing: A better way to study cancer than exists in mice or flat, 2-D, plastic culture dishes.

Those traditional laboratory research models are often poor substitutes for humans, as tumor cells don’t always behave normally in those environments. Growing cells in rigid, 2-D dishes, for instance, alters everything from their shape and structure to their biochemical signaling and gene expression, studies have shown. And mice, the most prevalently used animals in biomedical research, are unreliable tools for studying human biological mechanisms and diseases. A 2014 study in the American Journal of Translational Research, found the average rate of successful translation from animal models to clinical cancer trials to be less than 8%.

Living cells in 3-D

Sawyer and his collaborators postulated that a 3-D culture platform might provide a better model to mimic human tissues and organs. In 2015, they set out to build one.

Step one was finding the right matrix for the culture ecosystem. Sawyer and his team found inspiration in a common product that many people use every day: Hand sanitizer.

Although swollen in ethanol and fragrance, the microgel particles that comprise hand sanitizer struck them as the perfect substance for suspending cells and tissues. Remove the alcohol, perfumes and colorant, they reasoned, and you’d have a liquid-like solid with enough stability to support delicate tissue structures with enough space between the gels to create fluid channels, similar to a network of small blood vessels known as a capillary bed, through which nutrients and waste can flow.

“If you can believe that Bath & Body Works can put these small particles in there, I think you have to believe as engineers, we can put cells and tumors in there, and that’s really what we ended up doing,” Sawyer explained at a conference last year.

It took a few years of tweaking and tuning to get it just right, Sawyers says, but eventually they perfected their liquid-like formula for maintaining living cells in 3-D. They invented other tools to support the infrastructure, including their patented Darcy Plates, which use a pump-free suction system to transfer cell culture media (the chemicals needed to support cellular growth) into the microgel and remove waste products secreted by the cells. They also came up with micro-manipulator called BioPelle that functions almost like a tiny da Vinci surgical robot. When mounted to a microscope, researchers can pick up and place micro-tissues. Using it, they can, for instance, deposit cells, proteins and therapeutic molecules into their 3-D experiment to see how the cells react or pluck a particularly aggressive immune cell from culture for further analysis.

By 2020, the 3-D platform was generating buzz in UF research circles. Infectious disease researchers at the university adopted the tools to culture human lung tissue, infect it with the virus that causes COVID-19 and perform drug screenings. “We basically donated our entire infrastructure to the COVID pandemic to try to help find treatments,” Sawyer says.

By the summer of 2021, Sawyer and his colleagues decided to graduate their tools out of the lab and into an office in Gainesville’s Innovation District. They named the company Aurita, after Aurelia aurita, the common moon jellyfish, which was one of the first soft 3-D objects UF engineers printed nearly a decade ago. “We carry that (polymer) jellyfish with us as a reminder that life and jellyfish are very simple. We all know them — they’re soft, wet and squishy. They’re actually very similar in composition to the microgels we make,” Sawyer says.

The startup’s co-founders include Jack Famiglietti and Ryan Smolchek, who both worked with Sawyer on the technology when they were earning their doctorates in mechanical engineering at UF. In less than a year, they converted their office into a small manufacturing space with a biosafety level 2 lab, where they make all the gels for the 3-D culture system and assemble the Darcy Plates and other research products.

Walking through Aurita’s first-floor lab, Famiglietti, the company’s chief technology officer, shows off a tool that he and Smolchek built for heat sealing special membranes into the plates. The plates come in as injection-molded parts from various suppliers and are then washed, assembled and sent out in pouches, he says.

Aurita is on its second iteration of the Darcy Plate. While the original one they invented worked well in smaller-scale labs, such as those found at universities, the new ones are designed to better fit the automation and scale of larger pharmaceutical companies.

Brightly colored images of colorectal tissue, pancreatic cancer and malignant brain tumors — all cultured with Aurita’s 3-D system — adorn the startup’s office walls.

The pancreatic tissue is a particular source of pride. “The pancreas tissue is extremely hard to culture in most systems,” Famiglietti says. That’s because pancreatic tissue produces enzymes that digest food and under traditional culturing techniques, when pancreatic tissue is sliced open and dropped into culture media, it digests itself and dies. With Aurita’s 3-D-perfusion system and its continuous, one-direction, slow-flow media, researchers can essentially flush those enzymes away. “Instead of sitting in a pool of enzymes and digesting itself, we’ve actually been able to keep human pancreatic tissue up to 14 days still functioning,” he says.

Aurita has also been able to keep mouse pancreatic tissue alive and functional more than 10 days, Smolchek says. It usually dies within one to two days, but it’s easier to come by than human pancreatic tissue because the organ is rarely cut out in surgery. Consequently, mouse pancreatic tissue is predominantly used for studying diabetes and “being able to keep that alive for a long time is a huge benefit,” he says.

While Aurita started generating revenue just one year out of the gate and expects to be profitable in year two as well, Sawyer says it was never really his intention to launch a startup. “We did not set out on this mission to build a small company. We set out to build the tools to make new discoveries possible and to cure patients,” he says, but at certain point, interest was so great that they had to spin it out to support a “diverse group of researchers from different universities, different laboratories and even different disciplines.”

A decade after his cancer diagnosis, Sawyer is setting new goals. He recently joined Moffitt Cancer Center & Research Institute, heading up its new bioengineering department and he reckons that one day Aurita’s tools might provide a quantum leap forward for personalized medicine.

“It’s the ultimate in personalized medicine,” says Sawyer. “The idea is that you can take micro-tissues from a patient, with all of that patient’s history, all of their environmental exposures, all of the things that make that patient unique and look uniquely for therapies for that patient (and) not have to treat everybody as a statistical ensemble. The tools that we have in place, we’re always developing with an eye toward that.”

Key Elements of Aurita Bioscience’s 3-D Culture System

The Gel: Aurita's Liquid Like Solids culture material is similar to hand sanitizer and provides the 3-D matrix in which cells and tissues are suspended and studied.

The Plates: The membranes on the bottom of Aurita’s Darcy Plates — named after French engineer Henry Darcy who developed an equation for the flow of fluid through a porous medium — hold the 3-D-suspended tissue samples in place. The process works like a filter in a kidney dialysis machine, allowing fluids to flow up through the membrane but ensuring the solids and tissues stay put. “All the tissues in your body and all the tissues in any living creature are always kind of slowly being perfused with some kind of flow that’s washing away waste metabolites your cells are making and bringing in nutrients,” says Jack Famiglietti, co-founder and chief technology officer at Aurita Bioscience.

The Shovel: When UF researchers were using the 3-D system to study the virus that causes COVID-19 in lung tissue, they needed a way to locate the lung tissue in very precise positions on the Darcy Plates. They built a micro-manipulator they call the BioPelle, which comes from the French word pelle, meaning shovel. “We found it was pretty good at doing things even down to almost a single cell,” says Ryan Smolchek, co-founder and COO of Aurita Bioscience.

Tags: Technology/Innovation, Feature, Startups