Sergio Cancho Gonzalez

Sergio Cancho Gonzalez, PhD Student, University of Southampton

Interviewed by Mervyn Lewis, Associate Editor

Originally published in March 2021

What was your impression of mass spectrometry when you were first introduced to it?

I was introduced to mass spectrometry in the third year of my degree as part of an organic chemistry laboratory. The compound was synthesised and analysed by UV, NMR and GC-EI-MS and the objective were to elucidate the structure of the synthesised compound by using the information obtained from all techniques. By solving these exercises at home, it helped me realise that I enjoyed pushing arrows when solving GC-EI-MS problems, and it reminded me that I enjoyed solving puzzles when I was a child. I still see all of the analytical questions as puzzles that I need to solve.

 What persuaded you that mass spectrometry could be a good career option for you? Were you attracted by an application of mass spectrometry or excited by the prospect of developing it as an instrumental technique?

I have always been driven by application. Inside me I always have had the feeling of giving something back to society, and the more I read about the pharmaceutical industry, the more interest I got. At the same time during my degree, chromatography was something I wanted to pursue, and mass spectrometry slowly came on its own because of the relationship between both techniques. When I use them combined, I can start thinking about how to solve this puzzle and what is the best technique to approach it. Sometimes doing a method development for a new analytical application is like a Sudoku where you need to obtain all the numbers right (changes you make to the instrument) to ensure you can see the whole picture. I am happy I can solve this complex and challenging puzzles.

How did you go about finding your first opportunity in mass spectrometry?

My first opportunity was during my MSc project where after a talk with Dr Robert Bradshaw (University of Sheffield) I told him that I wanted to learn more about chromatography and mass spectrometry. The research projects offered by the university did not focus on this, so he helped me by launching a small project to investigate what is the best technique to quantify bisphenol A in food containers. This experience was exciting and helped me understand some of the challenges that occur during method development in the sample preparation, the separation (either liquid or gas chromatography) and the different detection (with flame ionisation detector, ultraviolet or electron ionisation mass spectrometry), or just using mass spectrometry on its own (matrix-assisted laser desorption/ionization mass spectrometry). By undertaking this project, it certainly helped me realise that it was what I wanted to do for the rest of my life. A few months later, I started a PhD Chemistry with Prof. John Langley (University of Southampton) where I am characterising and quantifying complex poly(ethylene) glycols and their impurities in drug formulations using supercritical fluid chromatography-mass spectrometry. This program has certainly reinforced that I want to do mass spectrometry until I retire (or longer).

In what application fields do you see new opportunities in mass spectrometry?

I think that the characterisation and quantitation of complex mixtures are still really challenging, especially in the -omics (e.g., metabolomics, petroleomics or polymeromics) due to the issues related to the ionisation and the ion suppression. The development of ionisation sources that can deal with matrix effect issues will certainly help in this area. Moreover, the dynamic range is an unevolved area that I think relates to the ionisation event. If you think of ICP-MS you can obtain up to 6-7 orders of magnitude of quantitation with an ESI-MS method rarely passes 3-4 orders of magnitude. A clear change of mind in how we obtain ions from molecules is certainly required to overcome this challenge. Data processing also requires deep research and a possible agreement between vendors and with individual research group software, i.e., a “Linux software for data processing”.

What is your opinion about the impact that automation and informatics will have on mass spectrometry?

This topic reminds to the past controversy when introducing autosamplers into the chromatographic system. I think we need to accept that technology is taking over and is there to help us as analysts to provide better and faster answers to complex questions. For example, in my PhD program, I am trying to separate the individual units of polymers (oligomers) to find the impurities present by minimising the ion suppression caused by the polymer. Using a data visualisation software has aided and sped up my data characterisation and allows me to easily spot impurities in the sample. At the same time, developing the quantitation has been challenging, as most of the current software cannot deal with the complex mass spectra obtained. Each of the oligomers ionises forming multiply charge species (I call them “small proteins”). If you overlap all these mass spectra you obtain a more complex one that relates to the polymer. Now imagine you have more than one polymer in your sample. I think this just a few examples showing that automation and informatics will help our daily life and will help the analyst to achieve the work-life balance that we need to produce better ideas to solve more complex problems. Automation has proved in the past that it can help in routine analysis, minimising workload and moving the attention to research rather than the actual quality control user. The latest advances in artificial intelligence will facilitate and reduce data processing, especially for the simplest samples used in daily routine analysis, minimising the turnaround time to provide results. The integration of these two will help to make mass spectrometry as a more competitor technique in a high throughput platform. As they mention in Yan Victoria Zhang and Alan Rockwood review in 2015: “The future for MS is a bright one, and automation will put wings on this giant elephant, enabling it to fly”.

Could you describe your views on career prospects in mass spectrometry for young people?

Following a career in mass spectrometry is being a scientist with a bit of engineering. You need to be able to have a clarity of thought to understand what the instrument is doing and how to solve the pieces when you need to troubleshoot it. Certainly, it is a multidisciplinary area where you need to discuss your knowledge with people from different backgrounds with little to zero knowledge of the area, even chemistry. I think with mass spectrometry you can easily combine your passion and your work. The pharmaceutical, the petrochemical, the food or the environmental industries are some of the most standard paths, but many other options are available from the waste management industry to archaeology or forensics, and still, there is a wide range of unexplored areas. I think that early specialisation in mass spectrometry is important to form a good next generation of mass spectrometrists, as a new group of more complex and challenging molecules are coming over to stay.

Acknowledgements

Sergio Cancho Gonzalez is a PhD Student at the University of Southampton working along with Prof. John Langley and Julie Herniman in a PhD program funded by AstraZeneca where he is characterising and quantifying poly(ethylene) glycols and their impurities in drug formulations using supercritical fluid chromatography-mass spectrometry.