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Mass spectrometry is a valuable tool for identifying and characterizing biomolecules, but the technology has limitations. Gary Siuzdak, director of the mass spectrometry centre at the Scripps Research Institute in La Jolla, California, and his colleagues set out to improve the technique's sensitivity and ease of use for analysing metabolites, single cells, biofluids and tissues. On page 1033 they describe how combining a nanostructure with chemical initiators made this possible.

What fuelled this work?

Mass spectrometry is commonly thought of as a mature technology, but it has constraints, including the breadth of molecules that can be analysed and its ability to separate molecules in a complex mixture. Our primary motivation was to move it forward.

Why use nanostructures to alter how the ions are generated?

To measure a molecule's characteristics using mass spectrometry, a gas-phase ion of that molecule has to be generated. My co-author Trent Northen wanted to develop a technique for more efficient ionization. We designed a silicon surface with nanometre-sized pores that can trap highly fluorinated initiator molecules (known as clathrates) that can be used to coat the molecule of interest. When the nanostructure is heated with pulsed laser irradiation, it efficiently vaporizes the molecule along with the initiatior, which ionizes the molecule.

What types of sample did you test first?

We focused on metabolites — small molecules generated during metabolism — as these have proved useful as biomarkers of disease. The most readily available were in our own biofluids, namely urine.

What applications do you find most interesting?

Metabolomics, the study of metabolites found in blood and urine, as well as the ability to profile single cells, are both of great interest to us. Because our approach involves minimal sample preparation, we believe it could lead to clinical applications. We also show that it can effectively image tissues — we use it to reveal the complex ionic profiles of developing tissue types in thin slices of mouse embryo.

What impact might this method have for biology?

This is a simple, high-throughput, robust and sensitive technology that will find uses in everything from determining the composition of microbial communities to profiling the structure of stem cells. To make the technology accessible to a wide audience, we've created a video guide.