TY - JOUR
T1 - Factorial-Design-Based Optimization of a Commercial MALDI-2 timsTOF Mass Spectrometer for Lipid Analysis
AU - Croslow, Seth W.
AU - Sirois, Chen H.
AU - Sweedler, Jonathan V.
N1 - Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG078797, by the National Institute On Drug Abuse of the National Institutes of Health under Award Number P30DA018310, and the acquisition of the instrument from the Office Of The Director, National Institutes Of Health of the National Institutes of Health under Award Number S10OD032242. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.V.S. is a CZ Biohub Investigator. S.W.C. acknowledges support provided by the Peixin He and Xiaoming Chen PhD4 Fellowship and the University of Illinois Block Grant Fellowship.
PY - 2025/3/28
Y1 - 2025/3/28
N2 - Matrix-assisted laser desorption/ionization mass spectrometry with laser postionization (MALDI-2 MS) has become an important technique for the analysis of a wide range of biomolecules. It has traditionally been limited to custom lab-built setups until the recent introduction of a commercial timsTOF fleX MALDI-2 system. A comprehensive optimization of the timsTOF fleX system for lipid analysis was performed using a factorial design of experiments (DOE). By examining 13 instrumental parameters across three full factorial DOEs, we performed over 1500 individual runs to assess the impact and cross interactions of these parameters on the lipid signal intensity. We found optimal values for both ion transmission and MALDI-2 parameters to maximize the signals within the lipid region. These results show that laser shot frequency, collision RF, and pre pulse storage were essential for enhancing lipid ion transmission, resulting in a nearly 5-fold increase in signal intensity compared to default parameters. For MALDI-2 optimization, positive and negative modes showed similar optimized values, with TIMS In pressure and laser power being crucial. Overall, optimization of ion optics and MALDI-2 resulted in signal enhancements of nearly 2 orders of magnitude for certain lipid species.
AB - Matrix-assisted laser desorption/ionization mass spectrometry with laser postionization (MALDI-2 MS) has become an important technique for the analysis of a wide range of biomolecules. It has traditionally been limited to custom lab-built setups until the recent introduction of a commercial timsTOF fleX MALDI-2 system. A comprehensive optimization of the timsTOF fleX system for lipid analysis was performed using a factorial design of experiments (DOE). By examining 13 instrumental parameters across three full factorial DOEs, we performed over 1500 individual runs to assess the impact and cross interactions of these parameters on the lipid signal intensity. We found optimal values for both ion transmission and MALDI-2 parameters to maximize the signals within the lipid region. These results show that laser shot frequency, collision RF, and pre pulse storage were essential for enhancing lipid ion transmission, resulting in a nearly 5-fold increase in signal intensity compared to default parameters. For MALDI-2 optimization, positive and negative modes showed similar optimized values, with TIMS In pressure and laser power being crucial. Overall, optimization of ion optics and MALDI-2 resulted in signal enhancements of nearly 2 orders of magnitude for certain lipid species.
UR - http://www.scopus.com/inward/record.url?scp=105001555268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=105001555268&partnerID=8YFLogxK
U2 - 10.1021/jasms.4c00424
DO - 10.1021/jasms.4c00424
M3 - Article
C2 - 40155311
AN - SCOPUS:105001555268
SN - 1044-0305
VL - 36
SP - 942
EP - 951
JO - Journal of the American Society for Mass Spectrometry
JF - Journal of the American Society for Mass Spectrometry
IS - 5
ER -