Imaging chemicals with unprecedented precision 

Our health is greatly affected by the environment around us. This can have long-term consequences, with factors impacting us during early development having the potential to affect our health later in life. 

For example, if pregnant mothers go through a period of malnutrition, then their newborn babies  may be undersized. However, even if they recover a healthy weight, they are still more prone to develop conditions such as diabetes much later in adult life.

At the Crick, researchers in the Physiology and Metabolism Laboratory are investigating how the developing body responds to stressful challenges in the environment, like a poor diet or a low oxygen supply.

A key area of focus for the team is studying the role of lipids or fats during development. 

“Studying lipid molecules in cells and tissues comes with its challenges,” says Alex Gould, group leader of the laboratory. “For many of the current methods you have to grind up the tissue sample into a homogeneous mix. This means that we lose really important spatial information about which types of cells and areas of the tissue contain the lipids of interest."

“Another challenge is that some lipids are fairly volatile, and so can disappear in the high vacuum of existing instruments for chemical imaging. This means they can be missing from the images, but it is then hard to know if this is because they were never present in the sample, or because they evaporated during the analysis."

To overcome these challenges, the Crick team collaborated with Ian Gilmore at the National Physical Laboratory (NPL), creator of a chemical imaging instrument called OrbiSIMS. The Crick and NPL researchers spent three years developing a cryogenic version of OrbiSIMS (cryo-OrbiSIMS) that would work with lipids and volatile molecules. 

This new imaging technique chills the sample down to -150 ºC, preserving even volatile chemicals and allowing the researchers to observe a very broad range of different molecules in tissues with unprecedented precision.

In the team’s most recent paper, they showed how the new cryo-OrbiSIMS technique can be used to image lipids and other molecules in human fingerprints, plant leaves and fruit flies.

“We were able to see in great detail exactly where different lipids are present in each of these delicate structures,” says Clare Newell, first author of the paper and a PhD student jointly at the Crick and NPL.  

“By testing our technique using diverse types of tissue samples, we’ve shown how it could be useful for a large number of research and industrial applications. For biomedicine, it could help researchers to see where specific lipids are present in tissue samples."

“Forensic scientists could use it to obtain additional information from fingerprints, such as what volatile chemicals or drugs someone may have been in contact with. Environmental researchers could also use the new method to see where polluting chemicals build up inside plants.”

Ian Gilmore adds: “Cryo-OrbiSIMS can map the chemical composition of tissues more comprehensively and more accurately than before and this has led us to some surprising findings."

“For example, we found that specific chemicals, which are present at the sweat pores in a human fingerprint, disappear if you look just a few thousandths of a millimetre away.”

Having shown that the new imaging technique works, Alex Gould’s team now plan to use it to answer fundamental questions about our biology and health, including how malnutrition during development affects lipids in the brain and skin.