Advancing automated mass spectrometry

Mass spectrometry is a sensitive technique for detecting and analysing the chemical properties of molecules. The technique is used widely to derive information to inform everything from disease diagnostics, tissue imaging to pollution control and chemical synthesis. Despite all the technique’s broad application and usefulness, it has some limitations when it comes to analysing the composition of complex molecules. 

“Intricate differences in molecular structure (vital to chemical function) can confuse detection methods leading to false negatives,” Prof Adam Trevitt (Chief Investigator), who directs the Laser Chemistry Laboratory at UOW, explained.  

“This is especially problematic for complex biological samples and medical screening applications. If you want to detect it all (all the molecules, I mean) – then you need to be able to deal with all that information. Furthermore, there is a whole class of molecules that don’t make themselves easy to detect. And some play tricks that mask their presence.” 

“However, recent breakthroughs in laser-based mass spectrometry methods, combined with ion mobility, now allow detection of subtle yet important structural features."  

“Our project aims to exploit these advances by developing new instrumentation and protocols with these enhanced capabilities thus accelerating advances in automated mass spectrometry, improved antibiotic detection and complex biomolecule screening.”  

The Discovery Project, titled New laser and mass spectrometry methods for selecting and assigning protonation isomers, is supported by $420,000 in funding over three years comprises four key objectives.  

The first goal is to innovate and build up new technology – broadly applicable laser-equipped mass spectrometry platforms exploiting ion mobility and laser-based dissociation for probing photochemistry of selected protonation-isomer ions in the gas phase. This will develop new fundamental science at the same time, which could lead to further – unexpected – breakthroughs. 

The research team will carefully establish experimental benchmarks to guide computational strategies for predicting electronic-state energies, the effect of protonation on the photostability of biochemically-relevant chromophores and small-molecule drugs. This includes measurement of excited-state proton affinity and ground-state protomer-selected basicity values.  

The project will also establish frameworks for understanding the excited-state structure and photostability of protonated heteroaromatics that rationalise relaxation and dissociation pathways. This is the essence of photostability. 

Finally, the project will produce predictive models of electrospray ionisation for rationalising and controlling protonation isomer distributions with this aim to broaden the application of mass spectrometry tools. 

“This project is timely as high-pressure ion-mobility techniques have developed to a point where protomer separations are available for ion-trap laser photodissociation experiments and our team of researchers and students are central to these developments,” Prof Trevitt explained.  

Working alongside Prof Trevitt on the project is Associate Professor William Donald from the University of New South Wales and Professor Christophe Jouvet, a Partner Investigator from the French National Centre for Scientific Research at Aix-Marseille University in France. Each Investigator heads laboratories that develop novel instrumentation to pursue new insights into reactive and dynamic molecular systems. 

“The outcomes of this project will provide significant and much-needed insight into the fundamental role protonation has on the photochemistry of biological chromophores while developing new analytical strategies for detecting protonation isomers and controlling electrospray ionisation in mass spectrometry.”  

Additionally, the project will train students in key technological areas including mass spectrometry, ion mobility separation, spectroscopy and lasers.  

“Australia – and indeed UOW – has a strong tradition of excellence in mass spectrometry and as the field continues to expand into biology and medicine, it is vital that we continue to train highly-skilled, world-class instrumentation experts. All our graduates are excellently positioned to engage and lead in the scientific and innovation economy,” Prof Trevitt said.   

• PROFESSOR ADAM TREVITT Read more about Professor Trevitt via his UOW Scholars profile