Creating the conditions to see things at an atomic level requires a special brand of engineering. Inside Melbourne’s Monash Centre for Electron Microscopy, the most powerful microscopes in the world capture molecular magic at work.
At 10 Innovation Walk on Monash University’s Clayton Campus, in Melbourne, there’s a building like no other in Australia. It’s the most stable building in the country, designed to protect its interior from all sorts of external influences, such as mechanical vibrations, noise, heat and even electromagnetic radiation.
The reason is that the building houses one of the most powerful electron microscopes in the world.
“If cars drive by, or the wind blows in the trees, this can cause vibrations that travel through the ground and could shake our instruments, so we have to isolate them in a special building,” says Professor Joanne Etheridge, Director of the Monash Centre for Electron Microscopy (MCEM).
In 2005, when Ruth Wilson – studio lead of Melbourne design firm Architectus – began to work on the MCEM design, very few structures in the world had been built with the stability requirements of these microscopes. “It’s one of a small handful of facilities in the world that have met these ambient conditions for the microscopes,” Wilson says.
At the start of the project, Wilson and Etheridge visited the best facilities in the world at the Dresden University of Technology, in Germany, and at the Thermo Fischer Scientific facility at Eindhoven, in The Netherlands.
“These were the facilities that had the most stable ambient conditions and the microscopes [in them were] performing to extraordinary levels,” says Wilson. “That set the benchmark for what we wanted to achieve.”
Within the MCEM building, which is sunk deep into the ground, there are mini buildings, each with its own walls, roofs and floors that are metres thick. Each microscope is nested in one of these mini buildings and sits on a floor slab of concrete that is one metre thick; the slabs, in turn, rest on 1.6m thick compacted sand beds. Isolation joints separate the slabs from the rest of the building structure, preventing vibrations from reaching the microscopes.
Room temperature is controlled with water-cooled radiative panels on the ceiling, rather than air exchange, to minimise mechanical disturbance from air-conditioning airflows. Airlocks minimise pressure gradients when researchers open lab doors and block acoustic vibrations.
And it’s not just about mechanical vibrations, heat and noise: electromagnetic fields can upset the microscopes too. Any moving large metal object creates an electromagnetic field, so elevators, cars and trams are all potential causes of disruption. Electric cables are troublesome too.
“Getting the electromagnetic fields to the lowest possible interference levels inside the building was the most challenging aspect of the building design,” says Wilson.
First, the architects looked at the surrounds of the proposed building. There was an electrified rail line within 1.5km of the site, which had potential to create interference, and six electrical substations within 100m, which were causing electromagnetic interference. The site contained what the architects describe as “significant piped services” in metallic pipes, all of which carried earth leakage currents.
Regular overflying aircraft and a nearby road, complete with speed humps, completed the picture.
Problems were solved case by case. The traffic route had to be reshaped to create a car-free ring around the MCEM site. Then the architects examined the electrical systems and power substations in all neighbouring buildings, and in some cases had to re-earth some electrical infrastructure.
“There was a lot of careful detective work and then a very meticulous cleanup of the site,” Wilson says.
Inside the building, replacing the elevator with a series of ramps to provide access to the upper levels was the easiest part. To minimise electromagnetic disturbance, labs are surrounded by tonnes of carbon steel, glass and wood to prevent electromagnetic fields’ penetration. The electricity cables that bring power to the building are shielded.
The resulting building is, from the outside, simple and elegant: a squat, perfect square. Inside are the reasons for all the architectural bother.
Electron microscopes allow scientists to visualise single atoms with a sub-angstrom resolution (an angstrom is 10-10m – one ten-billionth of a metre). Even minute vibrations could mean the difference between seeing one or not.
“If I want to take a photo of you, you would stand still for a moment, so when I click your image isn’t blurred,” explains Etheridge.
“When I image atoms, I want them to stay still too. They are 10,000 million times smaller than you, so you can imagine just how still they must be if the image is not to be blurred – everything around them must be still and silent!” she says.
In an electron microscope, a stream of electrons is accelerated and focused onto the specimen using magnetic lenses. The beam of electrons travels within a vacuum chamber to avoid any interaction with foreign particles along the way.
When the stream reaches the specimen, electrons either penetrate or bounce off and are detected to form images, using mathematical algorithms.
The mechanism is similar to an optical microscope, but electron microscopes use a beam of electrons rather than a beam of light. Because the wavelength of an electron is much smaller than that of a light photon, electron microscopes have much superior magnification and resolution. So while optical microscopes can resolve details on a scale of hundreds of nanometers, electron microscopes can resolve details on the scale of atoms.
The other difference between electrons and photons is that electrons have a charge and interact with matter in a different way than light.
“Each atom in the specimen comprises a cloud of electrons circulating a nucleus,” Etheridge says. “When the beam of electrons comes close to the specimen electrons, they are repelled by their like charge and scatter very strongly.”
There are two types of commonly used electron microscopes. Scanning electron microscopes (SEM) use low-energy electron beams to image the surface morphology (shape) and chemistry of a specimen.
In a transmission electron microscope (TEM), the electrons have enough energy to penetrate the sample, giving information about the position and type of atoms inside.
The arrangement of just a few atoms can have a profound influence on the properties of the material. Where atoms are and how they bond controls all the material’s features, from colour to strength to conductivity.
On the day Cosmos spoke to Etheridge, a world-first, ultra-high-resolution TEM – the “Spectra ϕ” – had just been delivered to MCEM by Thermo Fisher Scientific. It will be installed over the coming months. Several years in design and construction, “it will allow us to change the energy and shape of electron beams, so we can probe the matter in entirely new ways”, Etheridge says. “In addition, it will allow us to capture each and every electron that has scattered from the specimen. This means we don’t ‘waste’ electrons and therefore we don’t waste the information that they can give us about the specimen”
The new instrument will not only allow scientists to look at atoms; it will also give information about the energy state of electrons around the atomic nucleus.
“We’ll be able to see much finer features than we could see before, revealing subtle but critical details about where the atoms are and how they are bonded together,” says Etheridge. “This, in turn, tells us more about why a material has the properties it has.”
This means that researchers will be able understand much more about a material’s capabilities, and possibilities: whether it’s likely to conduct electricity; or whether it might store information in a memory device on a computer; or if it might emit or absorb light, and at what frequency.
“At one level, this reveals the sheer beauty of nature,” says Etheridge. “At another level, it opens up the possibility of engineering atomic arrangements to give us useful properties. This is the information that engineers need in order to design things like a more efficient solar cell, better batteries, more energy-efficient aircraft alloys, high-speed computers, biodegradable plastics, low-energy lighting and so on.”
When the beam of electrons hits the material under examination, the enormous transfer of energy damages the material. “It’s a destructive process,” says Associate Professor Georg Ramm, head of the Monash Ramaciotti Centre for Cryo-EM (cryogenic electron microscopy) facility. “You bombard your sample with lots of electrons.”
“When you look at the non-biological matter, often the damage is fairly slow,” says Etheridge. “So you have enough time to take images and learn about the specimen. But when imaging biological materials, the electron beam can damage them almost instantly.”
A revolution happened with the work of three biophysicists – Jacques Dubochet, Joachim Frank and Richard Henderson, who shared the Nobel Prize in Chemistry in 2017 for pioneering methods to image biological molecules – overcoming the “beam damage” problem. A critical part of this was the development of cryo-electron microscopy: finding a way to freeze biological samples without damaging them.
“Freezing and keeping the specimen cold is not trivial,” says Etheridge.
Jacques Dubochet discovered that biological solutions – for example, proteins dissolved in water – could be frozen at cryogenic temperatures using liquid nitrogen (−196 °C) without forming water crystals that could disrupt the molecules’ shape. That opened up the possibility of imaging a whole new world of molecules down to their atoms.
Another revolution was the advance in the mathematical algorithms used to create the images. And finally the “resolution revolution”, led by the development of a new generation of electron detectors.
“You can imagine that every electron that hits the specimen is doing damage,” says Etheridge. “So you want to detect every single electron that hits your specimen with absolute efficiency.”
Microscopes have certainly come a long way since the first optical instrument was built in the late 1500s. When the first electron microscope was made in 1931 by physicist Ernst Ruska and electrical engineer Max Knoll, at the University of Berlin, it had a magnification of four. Modern electron microscopes have a magnification of 10 billion.
“The exciting bit for cryo-EM is that we are now starting to look at the intra-cellular environment,” says Ramm. In a recent study published in Nature, a German research group was able to look at ribosomes – tiny, protein-synthesising particles made of RNA and protein – inside a cell.
“It’s quite amazing, and that’s where we want to head as well,” says Ramm.
Dr Manuela Callari is a Sydney-based freelance science writer who specialises in health and medical stories.