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High Resolution High Throughput Proteomics Platform for Cancer Research


EMSL Project ID
50473

Abstract

The objective of this project is to develop and evaluate a new high-throughput and ultra-sensitive platform that will enable more effective and higher throughput proteomics measurements to support and advance cancer research. The new platform will provide substantially higher resolution ion mobility spectrometry (IMS) separations than current platforms. The resolution of the IMS achieved will be greatly increased by using electric traveling waves applied to an extremely long path design based upon Structures for Lossless Ion Manipulations (SLIM), while also enabling very high sensitivity to be achieved. The platform will provide approximately two orders of magnitude improvement in measurement throughput for similar or better measurement coverage, quantification, etc. over conventional condensed-phase liquid chromatography-mass spectrometry (LC-MS) platforms, enabling thousands of samples to be analyzed in hours, rather than weeks as at present. We will also adapt and refine bioinformatics tools to provide automated and efficient data processing. The platform will be evaluated utilizing complex samples in terms of proteomic peptide/protein coverage, measurement throughput, CVs of replicate analyses and platform robustness and in comparison to conventional LC-MS platforms.

Project Details

Start Date
2018-08-28
End Date
2020-09-30
Status
Closed

Team

Principal Investigator

Yehia Ibrahim
Institution
Pacific Northwest National Laboratory

Team Members

Joon-Yong Lee
Institution
Pacific Northwest National Laboratory

Randolph Norheim
Institution
Environmental Molecular Sciences Laboratory

Xueyun Zheng
Institution
Pacific Northwest National Laboratory

Christina Stevenson
Institution
Pacific Northwest National Laboratory

Related Publications

Hollerbach A.L., A. Prabhakaran Nair Syamala Amma, A. Li, G. Nagy, C.P. Harrilal, C.R. Conant, and R.V. Norheim, et al. 2020. "Ultra-High-Resolution Ion Mobility Separations Over Extended Path Lengths and Mobility Ranges Achieved using a Multilevel Structures for Lossless Ion Manipulations Module." Analytical Chemistry 92, no. 11:7972 - 7979. PNNL-SA-152421. doi:10.1021/acs.analchem.0c01397
Li A., V. Garimella, and Y.M. Ibrahim. 2020. "A Simulation Study of the Influence of the Traveling Wave Patterns on Ion Mobility Separations in Structures for Lossless Ion Manipulations." Analyst 145, no. 1:240-248. PNNL-SA-145853. doi:10.1039/C9AN01509D
Nagy G., I.K. Attah, C.R. Conant, W. Liu, V. Garimella, H.P. Gunawardena, and J.B. Shaw, et al. 2020. "Rapid and Simultaneous Characterization of Drug Conjugation in Heavy and Light Chains of a Monoclonal Antibody Revealed by High-Resolution Ion Mobility Separations in SLIM." Analytical Chemistry. PNNL-SA-149352. doi:10.1021/acs.analchem.9b05209