TY - JOUR
T1 - Trapped ion mobility spectrometry and PASEF enable in-depth lipidomics from minimal sample amounts
AU - Vasilopoulou, Catherine G.
AU - Sulek, Karolina
AU - Brunner, Andreas David
AU - Meitei, Ningombam Sanjib
AU - Schweiger-Hufnagel, Ulrike
AU - Meyer, Sven W.
AU - Barsch, Aiko
AU - Mann, Matthias
AU - Meier, Florian
N1 - Funding Information:
We thank our colleagues in the Department of Proteomics and Signal Transduction for discussion and help, in particular D. Voytik, A. Strasser, J. Mueller, I. Paron, and C. Deiml. We acknowledge our colleagues H. Neuweger, N. Kessler, and S. Wehner at Bruker Daltonics in Bremen for their support in data processing and analysis. This work was partially supported by the German Research Foundation (DFG–Gottfried Wilhelm Leibniz Prize), the Novo Nordisk Foundation (Grant agreement NNF14CC0001), the European Commission (FP7 GA ERC-2012-SyG_318987–ToPAG), and the Max-Planck Society for the Advancement of Science.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - A comprehensive characterization of the lipidome from limited starting material remains very challenging. Here we report a high-sensitivity lipidomics workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS). Taking advantage of parallel accumulation–serial fragmentation (PASEF), we fragment on average 15 precursors in each of 100 ms TIMS scans, while maintaining the full mobility resolution of co-eluting isomers. The acquisition speed of over 100 Hz allows us to obtain MS/MS spectra of the vast majority of isotope patterns. Analyzing 1 µL of human plasma, PASEF increases the number of identified lipids more than three times over standard TIMS-MS/MS, achieving attomole sensitivity. Building on high intra- and inter-laboratory precision and accuracy of TIMS collisional cross sections (CCS), we compile 1856 lipid CCS values from plasma, liver and cancer cells. Our study establishes PASEF in lipid analysis and paves the way for sensitive, ion mobility-enhanced lipidomics in four dimensions.
AB - A comprehensive characterization of the lipidome from limited starting material remains very challenging. Here we report a high-sensitivity lipidomics workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS). Taking advantage of parallel accumulation–serial fragmentation (PASEF), we fragment on average 15 precursors in each of 100 ms TIMS scans, while maintaining the full mobility resolution of co-eluting isomers. The acquisition speed of over 100 Hz allows us to obtain MS/MS spectra of the vast majority of isotope patterns. Analyzing 1 µL of human plasma, PASEF increases the number of identified lipids more than three times over standard TIMS-MS/MS, achieving attomole sensitivity. Building on high intra- and inter-laboratory precision and accuracy of TIMS collisional cross sections (CCS), we compile 1856 lipid CCS values from plasma, liver and cancer cells. Our study establishes PASEF in lipid analysis and paves the way for sensitive, ion mobility-enhanced lipidomics in four dimensions.
UR - http://www.scopus.com/inward/record.url?scp=85077941171&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-14044-x
DO - 10.1038/s41467-019-14044-x
M3 - Journal article
C2 - 31949144
AN - SCOPUS:85077941171
SN - 2041-1722
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 331
ER -