CAT - A hybrid IMS-MS platform for ultrasensitive and high resolution glycan analysis
EMSL Project ID
49439
Abstract
The specific functions of glycans in a given biological process or pathogenic condition depend on their specific molecular compositions and structures. Accurate and quantitative measurements of glycomics profiles can greatly improve our understanding of the significant roles that glycans play in many common health problems and diseases. Despite technological advancements that have made mass spectrometry (MS) an essential tool for biomolecule analysis, unequivocal identification and structural characterization of glycans in complex biomatrix still remains to be fundamentally challenging tasks primary due to the extremely complex structures and the labile nature of glycans. The primary goal of this project is to develop a new ion mobility spectrometry (IMS)/MS-based instrument platform capable of detecting large and labile intact glycans and elucidating their structures with a much improved sensitivity and resolution. The new analytical platform will integrate a sub-ambient pressure ionization with nanoelectrospray (SPIN) source, a cyclotron IMS based on the structures for lossless Ion manipulations (SLIM) technology with a highly sensitive time of flight (TOF) MS by using electrodynamic ion funnel interfaces to achieve more than an order of magnitude better sensitivity and resolution as compared to any analytical tools currently available for glycan analysis. The biomedical applications of the new SPIN/SLIM-based cyclotron IMS/TOF MS instrument will be demonstrated by analyzing glycans in different cell lines representing different breast cancer subtypes to achieve unambiguous and complete structural elucidation of glycan biomarkers. The resulting instrument platform is expected to have broad biomedical applications that require high sensitivity and high resolution structural characterization of intact glycans.
Project Details
Start Date
2016-06-01
End Date
2016-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Wu H., L. Yi, R. Wojcik, T. Shi, and K. Tang. 2019. "A Separation Voltage Polarity Switching Method for Higher Sample Loading Capacity and Better Separation Resolution in Transient Capillary Isotachophoresis Separation." Analyst 144, no. 2:454-462. PNNL-SA-135251. doi:10.1039/C8AN01779D
Zheng X, X Zhang, N Schocker, RS Renslow, DJ Orton, J Khamsi, RA Ashmus, IC Almeida, K Tang, CE Costello, RD Smith, K Michael, and EM Baker. 2017. "Enhancing Glycan Isomer Separations with Metal Ions and Positive and Negative Polarity Ion Mobility Spectrometry-Mass Spectrometry Analyses." Analytical and Bioanalytical Chemistry 409:467-476. doi:10.1007/s00216-016-9866-4