Automated Microscope Gives a Look Inside Live Cell Populations

Automated microscope
It works like an MRI machine that generates images of cells from all angles using their refractive index and then compiles 3D images with the help of an advanced software© 2019 Alain Herzog

From now on scientists can look at how living cells function and react under various experimental conditions, in parallel and throughout a the cell’s lifetime. With the new 3D microscope unveiled today by EPFL spin-off Nanolive, researchers can observe the details of how cells operate – all the way down to their organelles. What’s more, the microscope is fully automated and doesn’t damage the cells being studied.

From now on, live cells will keep no more secrets. Scientists will be able to see first-hand how they function, including how their organelles interact and react to stimuli. Nanolive, an EPFL spin-off founded in 2013, has just developed a groundbreaking microscope that lets researchers watch living cells directly, continuously, and without harming them. That paves the way to important discoveries about biological processes that until now have been insufficiently understood because of the lack of a reliable way to observe them. The company’s new system comes together with a proprietary software for converting the images in 3D and making them easier to interpret, such as by displaying specific organelles in color.

Cells can be observed for hours, days or even weeks

With this next-generation microscope, called CX-A, scientists can watch living cell populations and zoom in all the way down to individual organelles with a resolution of <200 nm. Samples are prepared by placing the cells on a special 96 well plate. Scientists can rapidly set up their experiments by simply specifying how often they want images to be taken; the device then runs on its own. Data can be collected this way for as long as needed, with thousands of images taken over a period of several days or weeks. As a result, they can obtain unprecedented insights into how biological processes work, how organelles interact, and how mitochondria form intricate networks, for example.

The technology was initially developed by Nanolive’s CEO Yann Cotte while he was a PhD student at EPFL. It works like an MRI machine that generates images of cells from all angles using their refractive index and then compiles 3D images with the help of an advanced software. A rotating laser illuminates the sample at a 45° angle to produce a hologram, providing a unique look into cells under natural conditions. The method is non-invasive, manipulation-free, and interference-free, and the rotational scanning allows for 3D reconstruction with excellent resolution.

Traditional microscopes require the addition of stains or markers to cells, in order to add contrast and visualize them. Unfortunately, these compounds damage cells and cause them to die prematurely, shortening the length of time during which measurements can be taken. Nanolive’s technology requires no stains. “With our microscope, scientists can run experiments under a range of conditions and obtain high-quality images without adding fluorescent markers,” says Mathieu Frechin, head of quantitative biology at Nanolive. “The images generated using refractive index and the possibility to combine them with fluorescent signals enable scientists to follow over time dynamic and delicate cell processes – such as the membrane potential – of living subcellular structures like mitochondria. The signals reveal subtle variations in structure and activity that occur in response to drugs or genetic mutations.

Nanolive prefers not to disclose information about its revenue or fundraising, but it’s clear the company is doing well – it will hire 15 new people this year alone. The company’s first device hit the market in 2015 and is now used by companies around the world to perform R&D in biology, pharmaceutics, and cosmetics, as well as by universities for research and education. So what’s next for the company? “ We plan to double our headcount by next year so we urgently need to move into bigger offices” says Lisa Pollaro, chief marketing officer. “Besides that, we have plenty of research projects in the pipeline, although I can’t discuss them in detail. All I can say is that new breakthroughs are coming. ”