Electronics in the Electron Microscopy STP

DIY science: the Crick researchers making their own kit

When you’re working at the very forefront of science, theories are often developing so quickly that you’re left waiting for the experimental equipment to catch up. But waiting doesn’t come naturally to many Crick scientists, and all around our institute, there are creative DIY-ers making their own tools. 

You wouldn’t expect to see a leatherworking kit in the middle of a lab bench in a biomedical research institute, but that’s exactly what you’ll find next to the test tubes in the Apoptosis and Proliferation Control Lab, led by Nic Tapon.

It’s a tool used by postdoc John Robert Davis in his work examining how cells change their behaviour based on changes to their physical surroundings. Looking for something that could cut exactly the right size of silicone ring for a particular experiment, he trawled the web to find a tool from another trade to apply to his own.

He’s just one of the researchers here at the Crick finding that readily available lab equipment won’t always do. Whether it’s commissioning or building their own kit – or turning to Amazon – here’s how some Crick researchers are taking matters into their own hands. 
 

Mail-order making

What do you do? You turn to Amazon. There was a good amount of time spent combing the internet for something that was exactly the right size.
John Robert Davis

We still don’t know how the cells at the centre of our organs know to stop growing when the whole organ reaches its final size. Nic’s lab are studying this process and hope that we can one day use the knowledge gained from healthy organs to stop tumours in their tracks.  

John Robert’s work looking at cell behaviour involves growing cells on patterns which have been microprinted on to gel discs. As the gels cure, they harden, and monitoring how the cells respond to this hardening could show how cells are affected by the environment changing around them in the body.  

For the first step of this process, he needs to prepare identically sized gel discs and this requires cutting rings to surround them from sheets of silicone.  

But he had no tool to cut out identical rings each time. “What do you do? You turn to Amazon. There was a good amount of time spent combing the internet for something that was exactly the right size,” says John Robert.  

After some trial and error, he found the leatherworking kit. It cuts through the sheets of silicone to create uniform rings, ensuring that the experiment can be reproduced. 

Leatherworking images

John Robert Davis punching silicone rings at the lab bench

John Robert Davis at work 

Punching rings out of silicone with a leatherworking kit

Punching rings out of silicone

Silicone ring

A finished ring

3D printing the answer

But what happens when the problem is even more specialised? Miguel Munoz Ruiz is part of a group studying the immune system and investigating how the same mechanisms that fight off infections could be used to help the body fight off cancer.

“As scientists, we’ll always need tools that aren’t easy to find,” explains Miguel.  

As part of his work, Miguel needed to apply a cream to mice’s backs. The cream was watery and difficult to control and it turned out to be “just about impossible” to make sure that the amount and location of the cream were consistent.  

Miguel reached out to the Making Lab Science Technology Platform at the Crick, a team who work with researchers to design and build specialised devices, about making a dispenser for the cream.  

The dropper had to be soft enough to not hurt the mice’s backs, made of a material which wouldn’t react with any of the cream’s ingredients and dispense drops of cream which were the exact same size and shape every time.  

After less than a week spent testing materials and putting together a 3D sketch, the Making Lab used one of their 3D printers to make a prototype for Miguel. The prototype itself worked so well that he’s has been using it ever since. 

3D sketch of prototype cream dropper

Microwires for brain research

We had to become experts in so many fields – neuroscience, polymers, glasses, metallurgy. Basically, every single person is outside their comfort zone in some way.
Mihaly Kollo

When you can’t repurpose something and can’t have it made to order, the only option is to make it yourself. Romeo Racz and Mihaly Kollo, along with their group leader Andreas Schaefer and their wider team, study brain signals – specifically how mice respond to smells – and needed an extremely precise way to monitor brain activity.  

The team have developed incredibly thin microwires called jULIEs™. Five of them bundled together are not quite as thick as a human hair. The wires are advanced enough to be used to track signals around the brain but so thin that they can even bend around capillaries when they’re inserted. 

The project depended on bringing together a huge range of scientific knowledge. “We had to become experts in so many fields – neuroscience, polymers, glasses, metallurgy. Basically, every single person is outside their comfort zone in some way. The more interdisciplinary the team is, the higher the chance you have of making it work,” says Mihaly.  

Now that they have a process for quickly and reliably producing the jULIEs, with help from the Making Lab STP, it’s relatively easy to change the coatings on the wires’ tips to use them as different kinds of sensors.

By coating the tips in iridium oxide, for example, the wires become very sensitive to oxygen and can be used as pH sensors. Different tissues and even different kinds of tumours have different pHs, so the wires could be used as a minimally invasive way to map tumour locations inside the body. 

Along with Crick cancer researchers and with support from the Crick’s Translation team, the team is currently working with doctors at University College Hospital to investigate even more potential clinical uses for the wires.

 

Making your mark

Mickey Mouse branded onto a pollen grain

A familiar face branded onto a single grain of pollen using Lizzy and Yuxin’s microscope.  

Down in one of the Crick’s basement floors is the Electron Microscopy Science Technology Platform. There, senior laboratory research scientist Lizzy Brama and undergraduate sandwich student Yuxin Zhang have built a microscope which could save a huge amount of time and work for researchers using a scanning electron microscope.  

Scanning electron microscopy fires a narrow beam of electrons at a sample and gradually builds up a picture of the surface by measuring the signals which are reflected back. By scanning extremely thin slices of a sample, you can build up a 3D picture of the structures inside it. 

But this long and sensitive process produces enormous amounts of data. If you’re trying to image one neuron in a sample of brain tissue but can’t see it in detail before you direct the microscope towards it, how do you make sure that you’re not creating ten times – or one hundred times – the data you need?  

“The real secret to working with big data is to not make big data,” says Martin Jones, who leads the microscopy prototyping activities in the STP. Lizzy and Yuxin’s set-up helps to do just that.

Lizzy and Yuxin have built a light microscope which can be used to image a sample before it’s moved to the electron microscope. It uses a beam of infrared light to produce thorough but relatively low resolution images.  

But this same infrared beam can also be used to burn very small and precise patterns into samples. When the sample is then transferred to an electron microscope, the branded marks are still visible.  

Lizzy explained that the branding system is flexible enough that researchers could even draw a minuscule arrow or write notes directly onto a sample for future reference. “There really isn’t any limit on what you could draw with it.” 

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