Trailblazers of Medical Engineering

From brain sensors to gene therapy, the spirit of innovation thrives in the Andrew and Peggy Cherng Department of Medical Engineering (MedE). As MedE marks its tenth anniversary in 2023, its alumni are already making an entrepreneurial impact in health care.

Cherng MedE alumni Shane Shahrestani (MS '19, PhD '21), Alessandro Maggi (MS '16, PhD '17), Tatyana Dobreva (PhD '22), and Colin Cook (PhD '18) embody the mission of MedE and are trailblazers in translational medicine. Each of these four are founders or co-founders of a company working at the nexus of engineering and medicine, designing and fabricating devices and systems to make healthcare cheaper, more effective, and more accessible.

ENGenuity spoke with these entrepreneurs to learn about their companies, innovations, and what brought them to Medical Engineering at Caltech.

The sensor Shahrestani and colleagues developed at Caltech works like a metal detector for blood in the brain. As it circulates throughout our body, blood carries iron and charged ions to the brain. The StrokeDx sensor scans the brain to detect these ion distributions, picking up areas that might signal a pool of blood, a hemorrhage, or blockage.

Portable sensing technologies like ultrasound and electroencephalography (EEG) are already used in the medical field, but these aren't effective at diagnosing issues in the brain. Ultrasound can't image through a skull, and EEG can't distinguish between a bleed or a clot. StrokeDx's unique approach to brain diagnostics sidesteps these problems.

Central to the StrokeDx sensor is the technology of eddy current damping, which is used to detect cracks in airplane wings. In this technology, a sensor sends electrical currents through an airplane wing. If the wing has cracks, the electrical currents will be disrupted, allowing the sensor to pinpoint the exact location and size of the crack. StrokeDx is bringing eddy current damping out of aviation and into diagnostic medicine.

"I came to Caltech with no formal engineering background," says Shahrestani. "When I started working in the Micro Electromechanical Systems Lab (MEMS), I thought, how can I combine this cool airplane scanner with brain diagnostics?

"Caltech was the perfect environment for generating innovative ideas because you're getting IP help on one end, while learning cool new technologies in a MedE class, and then going to the lab and learning a whole different technology. There was so much creativity and freedom."

While working through the process of getting StrokeDx up and running, Shahrestani credits success, in part, to the environment of cross-collaboration within MedE, the assistance from Caltech's Office of Technology Transfer and Corporate Partnerships (OTTCP), as well as the guidance from his mentor, Professor Yu-Chong Tai [Anna L. Rosen Professor of Electrical Engineering and Medical Engineering], and other faculty like Professor Wei Gao [Assistant Professor of Medical Engineering].

After completing a seed round of funding, Shahrestani and co-founder Alex Ballatori are now working on optimizing their scanner for a clinical setting. "When you're dealing with the FDA, there's so much regulatory framework that you have to keep in mind in order to make sure you're moving forward correctly," says Shahrestani. "There are ten more steps you need to take before you can even make it to the step that you thought was just two steps away.

"Coming to MedE, I had no idea that I would leave with a device and have a startup. So, pursue that crazy idea because nothing's impossible."

Alessandro Maggi's company, Ecate (pronounced "eh-kuh-tay"), is developing a spinal cord machine interface to help the brain transmit information to limbs in the event of paralysis. When you have a spinal cord injury, the communication between your brain and your limbs is severed. With the neural probes being developed by Maggi and colleagues, information from the brain can be captured and sent to microscopic robotic devices and pressure sensors, creating a new channel of communication to the limbs.

"For effective brain implants, you must collect neurological information from as many areas as you can, and then you must identity and decode spatiotemporal patterns from those signals. This is an incredibly challenging task, especially if it needs to be done in real-time," says Maggi. "In our case, you've already made your decision; the white matter of the spinal cord simply mirrors that decision, and we're collecting that information to bypass your site of injury and restore voluntary movement."

For Maggi and Ecate, the biggest challenge is funding. "The technical challenges are always there but we've been trained on how to solve them," says Maggi. Unlike Artificial Intelligence or other technological applications, the return on investment (ROI) for neural brain interface devices is slow—the technology is still in development and the market is relatively small. There are opportunities to receive federal funding from organizations like the NIH and NSF, but the slow ROI for medical devices makes private funding difficult to obtain.

Although Maggi is now sharply focused on building Ecate, his path towards medical engineering was not direct. Maggi was originally a PhD student in biophysics, where he started working on microscale 3D scaffolds for bone growth in the lab of Julia Greer [Professor of Materials Science, Mechanics, and Medical Engineering]. At the time, the MedE department was not yet established, but after speaking with faculty in Electrical Engineering, Maggi switched from biophysics to medical engineering and became the first official MedE student. After completing his PhD, Maggi went to Apple to work on micro displays, gathering enough resources to eventually leave Apple, apply for an NSF grant, and turn Ecate into a reality.

"A lot of work was done on stimulating the brain in the '90s and 2000s, but not much on reading the brain. It will take some time before we have brain medical devices approved by the FDA and then usable for the average person," says Maggi. "But overall, medical engineering has a bright future, especially with neuro-related things. There are so many opportunities for improvement."

"I feel like the medical engineering program was focused on actually releasing something into the world. It had more of a build/iterate mindset," says Dobreva.

While working on an Alzheimer's-related project in the labs of Viviana Gradinaru and Matt Thompson [Assistant Professor of Computational Biology], Dobreva ran into a challenge related to blood collection. "It wasn't easy to get blood at Caltech. At other universities, you can walk across the street and there's an associated hospital," says Dobreva. "We also wanted to contact people after drawing their blood because we wanted to do a study where we tracked people's immune system across time. We realized we can't do that easily. So, we thought, why don't we take it into our own hands? Why don't we have people collect their own blood?"

As the COVID-19 pandemic evolved, the public gained a heightened awareness of the immune system, which generated business interest in the biotech space. This led Dobreva and her co-founder, David Brown (PhD '21), to pitch the idea that ultimately became ImYoo (pronounced "I'm you"), where patients can self-collect blood at home and ship it to a lab. Once the blood samples enter the lab, a technology called single cell RNA sequencing is performed—a process that captures a molecular snapshot of a person's immune system.

"We're looking at what's happening in the different immune cells in the blood. For instance, we're looking at what each individual t-cell or b-cell is doing," says Dobreva. "We're trying to capture medical data at the patient's convenience as they're experiencing significant medical events in their life, across time. This is a data set that's been missing and it's what the company is working on, building a longitudinal database across time in different immune conditions."

The single cell RNA sequencing data can lead to a better understanding of conditions like migraines, rheumatoid arthritis, and inflammatory bowel disease, just to name a few. Initially, the concept behind ImYoo was to anonymously match people's immune profiles and treatments to determine the efficacy of a specific drug or treatment. "The whole idea is that if you want to take a certain medication or therapy, you could ask someone who has a similar immune system as you," says Dobreva—giving rise to the company name, ImYoo.

ImYoo's most significant challenge is proving the clinical usefulness of single cell RNA sequencing, which is still a new and unproven technology. "There can be a lot of negativity, doubt, and discouragement, but knowing that we have partnerships and a team of people who took this on as their full-time job is very encouraging to see," says Dobreva. "Seeing my team persevering through the challenges and believing in what we're doing gets me up in the morning."

While attending a MedE seminar on oncolytic virotherapy by Dr. Yuman Fong, a cancer surgeon at City of Hope in Duarte, Cook was alerted to the major production bottlenecks facing the growing cell and gene therapy space. "There simply wasn't enough bioreactor volume globally to meet current, let alone future demand," says Cook. With the support of his advisor, Professor Yu-Chong Tai, Cook developed a new class of bioreactor and bioprocesses that dramatically increase productivity when compared to traditional methods.

"Conventionally, biologics like viral vectors have been manufactured in stir tank reactors, like how you would brew beer," says Cook. "This new process acts like an artificial lung and circulatory system, allowing a large number of cells to be packed into a tiny footprint."

Together, Cook, Tai, and Fong co-founded the company XDemics, which uses this new process to deliver an abundant supply of viral vectors for R&D, and eventually, clinical use. Instead of researchers burning precious time by making vector in multiple small batches, XDemics supports researchers with enough vector in one batch to run every experiment necessary.

"One of the things that the Medical Engineering department did right from its inception is the marriage of the entrepreneurial with the research," says Cook. "If you're in another field, you can be academically successful without whatever you're developing being commercially successful. But for a medical technology to be impactful, it must make economic sense in the marketplace to be reimbursed by insurance."

Now that the cell growth technology behind XDemics has shown to work in experiments, Cook and his colleagues face a familiar foe: financing. As XDemics transitions from a research and development company to a manufacturing company, business logistics are the next challenge. Cook received early support from Professor Tai via the Caltech Rothenberg Innovation Initiative, as well as initial funding from a federal Small Business Technology Transfer (STTR) grant, but finding a long-term funding partner will help XDemics accelerate real-world impact in the medical field.

"We want to allow researchers and academic startups to manufacture their biologic drugs so cheaply that they can perform more experiments and find really cutting-edge medicines," says Cook. "So, we're trying to transition from a paradigm of scarcity to one of abundance."