Miniaturizing the microscopes themselves

Miniature microscopes are tools that are revolutionizing fields such as neuroscience and are open sourced to researchers around the world.

They fit in the palm of your hand and don’t weigh more than a large coin, but their circuits allow something that in the field of neuroscience until 10 years ago seemed like a utopia: recording the activity of thousands of neurons that are activated at the same time in the brains of mice that can move freely. These are miniature microscopes that are generically called miniscopes (or “miniscopes”, in English), thanks to the fact that back in 2016 the American scientist Daniel Aharoni coined that term to refer to the small open source devices that he was developing with the team from his laboratory at the University of California, Los Angeles (UCLA).

Currently, some 15 academic groups from different countries are working on the development of their own models of miniscopes and there are expensive commercial versions, but the tiny instruments developed by Aharoni’s group are among the most widely used worldwide: they are sold already assembled. or in the form of a kit to assemble. “I estimate that some 700 groups from around the world have built or have one of our Miniscopes,” said the scientist in dialogue with the CyTA-Leloir Agency, and stressed that he uses the capital “M” to differentiate his devices from the rest of the microscopes in miniature.

“Our project is specifically aimed at building these tools in a way that every neuroscientist in the world can understand, afford and use. And that’s incredibly rewarding,” added Aharoni, whose research lies at the intersection of engineering, neuroscience and physics.

With the aim of introducing this new tool in Latin America, Aharoni came to Buenos Aires together with his “Miniscope Team” to give a four-day course on “miniature fluorescent microscopy” at the Fundación Instituto Leloir (FIL). Between December 12 and 15, 21 students from the region received scholarships to delve into the operation of these little devices that in the last 10 years have generated a revolution in neuroscience essays and of which there are three at FIL.

“All the devices launched by the group led by Aharoni are open source, that is, the design files are available in a public repository. Then, anyone who wishes can download and adapt them as they see fit”, said the Argentine Federico Sangiuliano, who joined the “Miniscope Team” in 2019, after having completed a two-year internship at the Laboratory of Physiology and Algorithms of the Brain directed by Emilio Kropff at FIL.

“We also have public forums for users to ask questions. There is a whole sense of community where people share knowledge and we try to lower the barrier of entry so that any laboratory in the world can use this registration technique. This is what sets us apart,” she added.

From his laboratory at the University of California, Los Angeles (UCLA), the American Daniel Aharoni directs the development of the “Miniscope” project, an open source miniature fluorescent microscopy platform that has already made it possible to record and analyze neural activity in small free-roaming rodents. (Photo: CyTA-Leloir Agency)

The Miniscope V4, the latest version, is a one-photon fluorescence microscope that weighs 2.6 grams and is 2mm high. “It records neuronal activity through fluorescence, that is, it lights up the brain as the neurons are activated, because they emit photons, and we record them with an image sensor that is in the microscope. That is recorded and then we can process the data,” reported Sangiuliano. The ITBA electronic engineer added that the platform also has external cameras – such as security ones – to be able to see the behavior of the animals. “It’s very important to not only record the activity in the brain, but also what the mouse is doing in order to correlate the information,” he said.

Aharoni, a PhD in Physics who specialized in the study of dark matter before focusing on the development of Miniscopes, is convinced that “for the future of neuroscience it is extremely important to be able to see what is happening in brains and How does that connect to the behavior of animals?

As for what is to come, the American was encouraged to predict a wireless future for the next five years: “There are groups that have achieved very good two-photon miniscope designs, so I think that these more advanced and complex devices will begin to be more used and that’s great. The other direction, which is what my group is working on, is based on making the same tools that we have today, but substantially smaller and without cables. This will allow us to capture truly natural behaviours, which is the approach we need to move towards”, he concluded. (Source: CyTA-Leloir Agency)