EPFL spin-off Nanolive develops microscope that inspects live cells

06 Jun 2023

Company has just opened office in Boston, MA, US, with the aim of going public.

EPFL spin-off Nanolive has developed a microscope that lets scientists look inside live cells – a feature they say is particularly useful for new drug discovery. Founded by CEO Yann Cotte in 2013, the firm has just opened a regional office in the US with the goal of going public.

Looking into the functioning of live cells reveals significant activity. Visible phenomena include tiny organelles working, as the process of apoptosis – or programmed cell death – runs its course, as T-cells search and destroy tumors, and more.

While these color-enhanced images can be fascinating to view for the uninitiated, they also contain much information for biologists. These are enabled partly thanks to research done by Cotte. He caused a stir in the imaging industry when in 2012, just after graduating from EPFL with a PhD in physics, he presented his new design for a microscope in a paper in 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.

Chance meeting

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.

Progress toward market readiness was rapd for Cotte’s development, 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. The answer: yes.

Cotte 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 had left the laboratory. “Their really positive feedback marked a turning point in the creation of our company,” he said.

‘Multiple applications’

Since then, the microscope has been used in many 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,” said 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 (such as the administration of a drug) and observe the response over time.

Considering the commercialisation process of the microscope, Cotte commented, “We knew from the start that Nanolive would be a long-term endeavor and we were only just beginning.”

And on fundraising, Cotte admitted 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,” said 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. The ultimate 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,” said Cotte.