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Made to measure

The vibrating razor cutting a thin slice of mouse brain

The vibrating razor cutting a thin slice of mouse brain

Carrying out pioneering research can require unusual custom-made kit. Katherine Nightingale speaks to some of the people who work in scientific workshops, and the scientists who benefit.

In a small room in the bowels of the MRC National Institute for Medical Research (NIMR), researchers in the Margrie Laboratory are using a serial microscope to image the entire adult mouse brain. To do this they need to sequentially cut thin slices of the brain (50 micrometres thick) using a vibrating razor called a vibratome. As each slice is removed, the microscope photographs the exposed surface of brain. After three days, they will have 3.2 terabytes of digital images, and a pile of about 350 brain slices sitting at the bottom of a container. While the digital data is safely stored on servers, what happens to the brain slices?

As the head of the laboratory Troy Margrie says, “We might want to keep particular slices of brain for further study, and the slices we want will be buried in a pile with no way of us knowing which one is which.” This is where the institute’s workshops come in.

Troy and his team are working with Martyn Stopps, who runs the NIMR’s electronic engineering workshop, to come up with an automated way of reliably collecting and cataloguing the brain slices. Developing the system has been a highly collaborative process, says Troy. “It’s a case of coming to Martyn with the research problem, and beginning a dialogue about how it can be solved.”

The brain slices are precious because they capture the result of a new technique developed by Troy’s lab. It involves detecting the activity of a single neuron, and then delivering a virus to it. The virus produces a fluorescent protein, which then spreads to reveal the brain-wide connectivity of that cell. When researchers stimulate visual pathways, they can see how the neuron responds, and, crucially, which of the many millions of cells in the brain are connected to it. By finding out how the brain is wired, Troy and his team hope to gain insights into what happens when the brain is mis-wired in conditions such as schizophrenia or autism.

By working together they have found a solution to the problem. Martyn and his colleague Nicholas Burczyk have designed a new device to handle the brain slices, as well as a slice storage system. They have combined this with an off-the-shelf robotic arm and control system, which they are now programming. The robotic arm grabs each brain slice as it’s released and places it into a specific location in the custom-designed storage carousel.

Specialised science

It’s not unusual to have to develop new technologies or adapt commercial equipment, says Martyn: “The nature of our job is to design new things and quite often that involves using new techniques we’ve never used before. You have to be really flexible.”

“The kind of science that happens here means we’re often making odd things — but that’s the point, it’s unique,” he says.

That sentiment is echoed by Owen Brimijoin, a researcher at the MRC Institute of Hearing Research (IHR). “Science by its nature can’t usually be accomplished with readily available off-the-shelf tools. If you’re doing it right then what you’re doing is new, so there’s no equipment out there that you can use.”

Owen’s research looks at how both hearing-impaired people and people with normal hearing make sense of the moving, three-dimensional auditory world. “We use information about where sound comes from to help us hear in noisy backgrounds, but hearing aids aren’t very good at telling you where that sound is coming from,” he says.

Part of the IHR's sound ring

Part of the IHR’s sound ring

It’s difficult to recreate real-world, dynamic situations in the lab in ways that are also valuable to researchers. To unravel how we perceive sound in three-dimensions, you need equipment that can keep track of both the position of a person’s head, and where the sound is coming from.

Owen has worked with colleagues in the IHR’s workshop to make a ‘sound ring’, a circle of loudspeakers in which a person sits, and has combined this with motion-capture technology. This means they can move sounds around in the ring dependent on the way someone is facing. “This is helping us to create a realistic picture of how people listen in the real world,” says Owen.

“The structure was designed by our workshop and made externally, but all the wiring, electronics and programming was done in-house. That’s immensely valuable. Having people around to spot problems is absolutely instrumental.”

In-house expertise

At the other end of the spectrum from robotic arms and motion capture, back at the NIMR, head of the mechanical workshop Alan Ling and his team produce anything from intricate metal components that focus laser beams to one-off housing boxes for microscopes.

“We make things that scientists can’t buy, or modify them to suit. We’re pretty well equipped — we can make most things here.”

Sometimes scientists bring sketches of what they want down to the basement workshop. “We’re below the canteen, so lunchtime is always a busy time with people popping down to say ‘Oh, can you just do this?’”

 

 

Listen to the audio for a quick tour of Alan’s workshop and his thoughts on working with scientists to produce custom-made kit.

For Andrew Bailey, Alan’s workshop could save him precious hours. They’re working together to produce a relatively simple piece of equipment that will mean he can transfer his drosophila fruit flies to new housing tubes in batches of 40, rather than one.

Alan’s seven-strong workshop also produced all the trays in which the flies’ tubes are housed, as well as a system for knocking out he flies with carbon dioxide so they can be looked at under the microscope.

Alan Ling in his office

Alan Ling in his office

“Often the equipment is not the kind of thing that would be worth an external company making — there are only so many fly labs in the world — so having a workshop onsite is crucial,” says Andrew.

Commissioning external companies would be expensive, says Martyn. And it also requires careful briefing to make sure the product is exactly right. Having people onsite means that the process can be iterative.

“We’ll build a prototype and then check that with the research team — sometimes the prototype might do the job, but with others we’ll need a few rounds of back and forth,” he says.

This in-house capability to develop new scientific instruments means that researchers can do experiments in emerging areas of science that would otherwise be out of reach.

As Owen sums it up: “People in-house have a better understanding of what you do than anyone outside could. They know exactly what it is you’re trying to do.”

Katherine Nightingale

A version of this article was first published in the Spring 2014 issue of Network magazine. 

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