In this episode of Science Futures, we hear Max Lennart Feuerstein.
Max is a doctoral student at the Institute for Analytical Chemistry at the University of Natural Resources and Life Sciences (BOKU) in Vienna. He works with Ion Mobility Mass Spectrometry (IM-MS) and is mainly involved in the development of new acquisition strategies and appropriate applications partly using prototype hardware and software for IM-MS in the field of metabolomics.
In this interview, Max tells us more about his research and how it might lead to technical improvements in data acquisition workflows.
Can you tell us more about your research?
Max Lennart Feuerstein (MF): The coupling of ion mobility to mass spectrometry (IM-MS) is not a new concept, but there have been some substantial technical developments, including the introduction of several commercial instruments, in recent years. In addition to adding a separation dimension, IM helps determine the collision cross section of a molecule, which can be simplified as the rotating cross section (“size”) of a gas phase molecule. This property can be used to increase confidence in characterizing or confirming the identity of an unknown analyte molecule.
However, precise mass spectra and fragment spectra are the most relevant “markers” for the correct identification of analyte molecules in mass spectrometry. Analyte molecules can be fragmented in MS instruments (eg, time-of-flight quadrupole MS (QTOF), which we are working with), and these fragment ions can then be detected. The fragment model is highly selective for a single molecule under controlled conditions, contains information about the structure / substructures of a molecule and can be compared to databases containing such spectra to support the identification of ‘analytes.
When handling complex samples, complete separation of all analytes using one technique may not be possible. This can make it difficult to generate clean fragment spectra for all analytes using MS. One way to overcome these limitations is to use multi-stage MS instruments (composed of multiple MS devices, e.g. quadrupole, collision cell, and TOF are part of a QTOF instrument), allowing us to select and d ‘isolate a “precursor ion” (our analyte) using the quadrupole as a mass filter, fragment this molecule in a collision cell and use the TOF MS to detect the fragment ions. We could find ourselves in a situation of compromise between the selectivity (“clean spectra”) and the coverage of our method. IM-MS is another possibility to improve analyte separation / reduce the amount of “interferences” (contributions from other molecules) in the generated fragment spectra, especially because IM separation is quite fast. and reproducible (at least using drift tube instrumentation).
In this project, we combine quadrupole isolation and IM separation on an Agilent drift tube IM-QTOF instrument to improve selectivity. To this end, we use prototype hardware and software to control the quadrupole of the instrument.
What are the main or most important results of your research?
MF: In analytical chemistry, we often suffer from a gap between the selectivity and the coverage of the methods developed – this means that we obtain high quality information for only a few metabolites of interest, or we extend our methods and try to provide data. for as many metabolites as possible. Technical developments help us to construct generic methods for a wide range of analyte molecules while maintaining a high level of selectivity. The combination of high resolution MS and instant messaging in particular is considered a suitable next generation toolkit for this type of workflow. By nesting MI between chromatographic separation and MS detectors, we were able to establish a method for our instrumentation that allows us to analyze a wide range of metabolites in an untargeted manner with a high level of selectivity. We are optimistic that this may increase the level of confidence we can place in our results.
What global or societal challenges does your research address?
MF: Our understanding of the world is changing extremely rapidly, in part because humanity is producing more data than ever before. However, high quality data sets are needed to allow solid conclusions to complex scientific questions. The time spent measuring and evaluating these data remains a limiting factor in answering many research questions. Especially in the context of the life sciences, scientists rely heavily on in-depth analysis of large sample cohorts, and MS is one of the main ‘workaholic’ technologies that can help describe the reality of life. measurable way.
By using MS, we generate huge datasets, and the processing, preservation and interpretation of the data is not a trivial task. Especially when analyzing complex samples; differentiating between data containing relevant information and data which is either irrelevant, redundant, or simply an artifact of the method used, can be difficult. Our research could be seen as a piece of the puzzle that attempts to speed up measurement times while maximizing data quality through technical improvements to data acquisition workflows.
Was it easy to access the technology needed for your research?
MF: I have been fortunate that the instrumentation has not been overloaded with measuring hours over the past year, but that can change quickly in our institute where many diverse projects are being undertaken simultaneously. In general, we are very dependent on good laboratory management because several researchers use the same instrumentation.
Have you had the opportunity to interact with industry and businesses to advance your research?
MF: The research project I am working on is financially supported by one of the Agilent Scholarships for Academic Relations. I applied for a position which has been supported by this project from the end of 2018. In addition, the hardware and software is developed by Agilent, and we receive technical support from the developers and have discussions and meetings regularly.
I would definitely consider working with industry in the future. Besides the opportunity to test technological prototypes and develop applications and acquisition strategies, I enjoyed the scientific discussions with the instrument developers and learned a lot from this collaboration.
What challenges do you face as a doctoral student in understanding your options at the end of a doctorate?
MF: I am still in the middle of my PhD studies and I am confident to build promising collaborations during my time at BOKU that will help me find interesting follow-up projects, for example as part of a post-doctorate position. From discussions with former colleagues and other scientists, I have a feeling that the combination of short- to medium-term project positions in academia and the required level of flexibility might be difficult at some point. given.
As a result of your studies and research, what will be your career destination?
MF: For me, analytical chemistry, especially as it relates to IM-MS and related techniques, is a really exciting area of research. This ranges from fascinating technical developments, detailed studies helping to generate a fundamental understanding of the structural properties of individual molecules, to the analysis of large cohorts of complex samples, for example, in the context of environmental, medical research. or related to biotechnology. I hope to be able to contribute more to university research in this area in the future.
How prepared do you consider yourself for real-world accomplishments?
MF: I might be a little naive, but I’m not at all worried when I think about the period after my doctorate. Besides a very extensive training in analytical chemistry, I will have a broad base in different fields of natural sciences and related methods after completing my studies. For example, working with large data sets requires certain skills in statistics, calculation methods or programming and for successful interpretation of the data, biological knowledge may be required. We will see how things will evolve in the end, but I am optimistic!
You can find the previous installment of Agilent Science Futures, an interview with Alexandra Richardson, here.
