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31.05.23 - EPFL spin-off Nanolive has developed a microscope that lets scientists look inside live cells – a feature particularly useful for new drug discovery. Founded by CEO Yann Cotte ten years ago, the firm has just opened a regional office in the US with the goal of going public. Your first glimpse into the functioning of live cells is a mesmerizing experience. You watch as tiny organelles get to work, as the process of apoptosis – or programmed cell death – runs its course, as T-cells search and destroy tumors, and much more. While these color-enhanced images are fascinating to view for the uninitiated, they also contain a gold mine of information for biologists. And they’re made possible thanks to research done by Yann Cotte. He caused a minor sensation in the imaging industry when in 2012, just after graduating from EPFL with a PhD in physics, he presented his new microscope in a reference publication in the prestigious scientific journal Nature. His design was the first to combine holography and laser scanning in the same device, resulting in clear 3D images well below the existing resolution threshold. Initially intended as a proof of concept by characterizing materials, Cotte’s microscope elicited both intrigue and interest. A chance meeting paved the way to biology Cotte developed the basic technology behind his microscope as well as the first prototype as part of his PhD thesis in the early 2010s, working with then-fellow PhD student Fatih Toy, today an associate professor of biomedical engineering at Istanbul Medipol University. Their breakthrough was an entirely novel calibration system containing a thin layer of aluminum with several nanoscopic holes. The holograms are assembled and processed by algorithms to reconstruct 3D images. Then the images are “sliced” virtually, in process similar to that of a scanner, so as to give scientists precise views of a given object. “I was really proud of what we accomplished,” says Cotte. Some highly promising innovations never make it to market since they lack a viable application, and others end up spending years in the R&D stage. Yet things went quickly for Cotte, thanks largely to a chance meeting. During the peer review process for their publication in Nature, a professor from Johns Hopkins University asked Cotte if his microscope, intended as a proof of concept by characterizing materials, could be used to examine neurons. His answer: yes. Once back in Switzerland, he had to work quickly to get some samples ready and recalibrate the machine. Although the microscope was still in its early stages, and the data still took several hours to collect, when the Johns Hopkins professor and his colleagues tried it for the first time, they obtained never-before-seen images of live cells in their natural environment with no contrast agents or fluorophore. The professors’ enthusiasm was contagious. This enabled Cotte to make the leap from photons to biology even before his microscope left the laboratory. “Their really positive feedback marked a turning point in the creation of our company,” he says. It was at that point that he realized the full potential of his invention. Since then, the microscope has been used in a host of applications, ranging from immuno-oncology and new drug discovery to personalized medicine. “We held a number of discussions with biologists, pharmaceutical scientists and medical doctors to pinpoint their needs and identify the next steps,” says Cotte. He and his team also developed software to automatically recognize specific objects, quantify them and compare them. One version of the microscope has a screening feature that lets scientists observe several dozen cell samples in parallel, record how cells respond to various stimuli (like the administration of a drug) and observe the response over time. I have a lot of respect for all entrepreneurs. Fundraising for a new business is very stressful and you have to invest a lot of time and energy. Yann Cotte “We knew from the start it’d be a long-term endeavor” Startups are by definition high-potential businesses, and this was what Cotte kept in mind as he went through the different business development stages. The way he describes those initial years – with an enthusiastic smile – almost suggest it was a walk in the park, and that the leap from being an academic researcher to a CEO was a snap. “We took it one step at a time,” he says. “We knew from the start that Nanolive would be a long-term endeavor and we were only just beginning.” When asked about the thorny issue of fundraising, Cotte admits that it’s “still a challenge.” The firm has carried out three funding rounds since it was founded – including one in 2022 that brought in $20 million in venture capital – and has obtained quite a bit of startup funding from entrepreneurship programs and competitions in Switzerland. “I have a lot of respect for all entrepreneurs,” says Cotte. “Fundraising for a new business is very stressful and you have to invest a lot of time and energy.” He points out that he was lucky with his timing, since he ended up talking to potential investors in the middle of the pandemic. “There was a lot of interest in healthcare-related businesses at the time,” says Cotte. “People saw meaning in what we were doing. I think it’d be harder to raise funds today in the current geopolitical climate.” Watching and analyzing T cells attack cancer cells in real time The goal is an IPO Today Nanolive has about 70 employees, up from 45 in 2021, and with its new office in the US is targeting an IPO. “Our Boston site is far from a guarantee that we’ll be able to go public, but it brings us closer to the vast North American market, enables us to serve customers more quickly and gives us an opportunity to soak up the US business culture.” Taking a lab discovery to market entails developing a broad range of skills and assuming a variety of roles. So what’s Cotte’s secret for navigating the pitfalls of business development without breaking his stride? One could be his excitement at seeing how many applications there are for his device. And he’s quick to clarify that he’s motivated not by the market potential, but rather because he’s “genuinely amazed at what researchers are doing with our microscope, the things they’re studying and the discoveries they’re making.” What advice would Cotte give to entrepreneurs just starting out? “You’ll inevitably make mistakes. So make them as early as possible when the consequences won’t be as serious.” Cécilia Carron