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Ion Mobility Mass Spectrometry to Unscramble Complex Biological Samples

English title Ion Mobility Mass Spectrometry to Unscramble Complex Biological Samples
Applicant Bigler Laurent
Number 183310
Funding scheme R'EQUIP
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Organic Chemistry
Start/End 01.09.2019 - 31.08.2020
Approved amount 479'561.00
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All Disciplines (3)

Discipline
Organic Chemistry
Molecular Biology
Embryology, Developmental Biology

Keywords (6)

structure elucidation; natural product; quantification; biotransformation mechanisms; high-resolution mass spectrometry; ion mobility

Lay Summary (German)

Lead
Neue Methoden zur exakten Charakterisierung von Molekülen in komplexen biologischen Gemischen mittels Ionen-Mobilität Massenspektrometrie.
Lay summary
Die Bestimmung und Identifizierung von organischen Molekülen in komplexen Gemischen ist ein zentrales Gebiet in den Naturwissenschaften. Durch die Identifizierung und Quantifizierung von Molekülen und mit Hypothesen zur Funktion dieser Verbindungen können Voraussagen über biologische Systeme getroffen werden. Dies können zum Beispiel Moleküle sein, die für eine Krankheit charakteristisch sind oder auch Moleküle, die für die Toxizität einer Pflanze verantwortlich sind. Ein zentrales Problem ist jedoch in diesem Zusammenhang, dass komplexe Gemische oft Zehntausende von Molekülen umfassen. Dieses Projekt fördert die Anschaffung eines neuen Instrumentes, welches mit herausragenden Methoden diese komplexen Gemische auftrennen kann, und so die Identifizierung von Verbindungen mit hoher Gewissheit und Genauigkeit erlaubt. Dies erlaubt Anwendungen in der Chemie, Toxikologie, Pharmakologie, den Umweltwissenschaften, der Forensik, und der klinischen Medizin.
Direct link to Lay Summary Last update: 29.08.2019

Responsible applicant and co-applicants

Associated projects

Number Title Start Funding scheme
163151 Directing Neurite Outgrowth through Synthetic Natural Products 01.10.2015 Project funding (Div. I-III)
172977 Diversity and evolution of the PAO/phyllobilin pathway of chlorophyll breakdown 01.07.2017 Project funding (Div. I-III)
160051 Copper availability, methanobactin production and methane oxidation in two Swiss lakes: Constraints on copper acquisition by methanotrophic bacteria 01.06.2016 Project funding (Div. I-III)
185026 Embryonic Diapause: pluripotency on hold? 01.04.2019 Project funding (Div. I-III)
154430 Investigations on the obligate leave nodule symbiosis 01.01.2015 Sinergia

Abstract

Ion mobility is a technique used for the separation of ions according to their collisional cross sections. It is used as stand-alone device (e.g. in airport safety) or in combination with mass spectrometry. In case of the latter, Bruker Daltonics GmbH recently developed a new instrument called timsTOF, combining a trapped ion mobility device with remarkable resolution (4x higher than the Waters Synapt G2-S, current market-leading instrument) and a high-resolution tandem mass spectrometer. The ion mobility (drift time measured in V•s/cm2) offers an futher separation dimension in addition to chromatography (retention time), and mass spectrometry (m/z value and Bruker’s unique isotopic pattern fidelity (True Isotopic Pattern or TIPTM)). Several outstanding properties of ion mobility have attracted our attention: the possibilities to (1) separate isomers and determine collisional cross section, (2) differentiate substance classes such as e.g. phospholipids from steroids or flavonoids, and (3) suppress chemical background for more accurate and sensitive quantifications. The seven group leaders that join their efforts with this application are confident that the Bruker timsTOF could help solve problems related to their very diverse research fields ranging from fundamental chemical discovery and plant sciences to applied research in forensics and environmental sciences. More specifically, they hope to bring their research to new frontiers for the following reasons (the project descriptions are presented in the scientific part): -In natural product research, the separation of isomers and the determination of collisional cross sections are essential aspects in the structure elucidation of small molecules. Coupling of ion mobility to high-resolution MS and MS/MS not only allows for the acquisition of distinct MS/MS spectra of (co-eluted) structural isomers, but the possibility to accurately calculate collisional cross sections as unique molecular descriptors also opens up new opportunities for structural annotation. Overall, this procedure enables a more reliable structure prediction. In natural product research, this greatly improves the quality of the assessment of structure-activity relationships for e.g. the characterization of new acylpolyamines in spider venom, potential drug candidate in the treatment of neurological disorder, pain or cancer (LB). Similarly, in environmental chemistry research, a distinction of structural isomers supports the development of more accurate structure - biodegradation relationships (KF). Other areas of application are the discovery of plant metabolites showing potential biological activity (KG), the study of catabolism of chlorophyll (SH) and the examination of the role of flavonoids in plant growth (CR).-The annotation of known compounds and the detection of unknown metabolites of a specific substance in complex samples is seriously facilitated in the trapped ion mobility spectrometry device. Different substance classes can be distinguished because they show different ion mobility properties. In combination with UHPLC and HR-MS/MS, this additional separation step enables or at least facilitates the annotation of components in complex mixtures. A rapid and complete characterization of complex samples will allow, e.g., an in-depth monitoring of the biotransformation of chemical contaminants (KF). It will also be possible to detect estrogens spread by agriculture in complex tissue and soil samples (SU). In forensics, the metabolites of the constantly growing number of new psychoactive substances can be localized in a straightforward way by ion mobility separation (TK).-Finally, ion mobility will increase the sensitivity and the quality of quantitative analyte determination in complex matrices such as blood, urine, surface water or soils performed with UHPLC-HR-MS. The ubiquitous chemical background such as lipids and plasticizers have a different drift time and can be suppressed. This may be particularly useful for the quantification of the degradation products of synthetic substances of industrial origin in the environment (KF) or the quantification of estrogens from agriculture in soils (SU). These analytes have to be detected in very small quantities in highly complex matrices containing a mixture of several hundreds or even thousands of compounds.Given that no such instrument is currently in operation in Switzerland, and for the many reasons mentioned above, there is no doubt that the Bruker timsTOF instrument has the potential to catalyze research in several areas, enabling new discoveries across the molecular sciences, from natural product discovery, environmental chemistry, to scientific forensics.
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