Seminar - Hua Tian

photo of Dr. Hua Tian
December 9, 2019 - 12:00pm
Location: 
601 Fairchild

Department of Chemistry

Penn State University

Host: Brent Stockwell

Title: Extending the Chemical Vision in Life Science by Cluster Time-of-Flight Secondary Ion Mass Spectrometry Imaging (ToF-SIMS)

Abstract: Millions of biomolecules (e.g., metabolite, lipid and peptide/protein) in any given biological system form an intricate concerted network, expressing specific behavior of cells in a healthy or diseased state. The only route to understanding molecular mechanisms is to characterize the significant biomolecules in their native environment with high chemical specificity and subcellular spatial resolution. Particularly, the advance of imaging mass spectrometry would seem to offer the possibility to chemically map multiple biomolecules across different omics in a single sample preparation and single run. However, owing to the limitation in sensitivity, mass range and spatial resolution, it remains a holy grail for a single instrument to ionize all the molecules at the subcellular level. In addition, the sample preparation for each omics is usually not compatible with measurements for other omics.

Coupling gas cluster ion beams (GCIB) to secondary ion mass spectrometry (SIMS) has shown great potential to detect biomolecules with high sensitivity and extended mass range 1-3. Especially, the development of a high energy GCIB 4 and source modifications to enable the formation of water cluster beams 5 has been successfully used to characterize metabolites and intact lipids up to m/z 3000 in single cells. The high energy water cluster ion beam, 70 keV (H2O)34,000+ specifically has further enhanced the ionization by up to a few orders of magnitude, facilitating submicron sampling in cells/tissue. Surprisingly, multiply charged peptides are generated using an acidified water cluster beam. Using a cryogenic sample handling system 6, we demonstrate the capability of resolving various biomolecules at 1 µm resolution in several frozen-hydrated animal tissues, e.g. energy-related metabolites, intact lipids and peptides with a mass range of up to m/z ~5000. Especially, the low abundance lipids, such as phosphatidylglycerol, PG (34:1), phosphatidylserine, PS(36:1) and phosphatidylethanolamine, PE(36:4) are mapped in brain tissue for the first time. This capability is attributed to the up to ~20 times enhancement in signal compared with other GCIBs. The N-acetylated myelin protein is mapped by doubly charged fragments at m/z 917.40, 931.43 and 1082.43. This setup, 70 keV water cluster beam with cryogenic analysis, has provided an unique opportunity to scrutinize the biomolecules belonging to different omics at their close-to-nature state and highest achievable resolution (~1 µm), offering new insight into the true chemical picture of the biosystems.

References:

(1) Tian, H.; Sparvero, L. J.; Amoscato, A. A.; Bloom, A.; Bayır, H.; Kagan, V. E.; Winograd, N. Anal. Chem. 2017, 89, 4611-4619.

(2) Angerer, T. B.; Blenkinsopp, P.; Fletcher, J. S. Int. J. Mass spectrom. 2015, 377, 591-598.

(3) Berrueta Razo, I.; Sheraz , S.; Henderson, A.; Lockyer, N. P.; Vickerman, J. C. Rapid Commun. Mass Spectrom. 2015, 29, 1851-1862.

(4) Tian, H.; Sparvero, L. J.; Blenkinsopp, P.; Amoscato, A. A.; Watkins, S. C.; Bayir, H.; Kagan, V. E.; Winograd, N. Angew. Chem. Int. Ed. Engl. 2019, 131, 3188-3193.

(5) Sheraz, S.; Tian, H.; Vickerman, J. C.; Blenkinsopp, P.; Winograd, N.; Cumpson, P. Anal. Chem. 2019, DOI: 10.1021/acs.analchem.9b01390.

(6) Fletcher, J. S.; Rabbani, S.; Henderson, A.; Blenkinsopp, P.; Thompson, S. P.; Lockyer, N. P.; Vickerman, J. C. Anal. Chem. 2008, 80, 9058-9064.

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