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.
Comprehensive analysis of glycans in biofluids can significantly improve our understanding of the structure diversity and the functions of individual glycans as changes in glycan structures and abundances or the appearance of new glycans are associated with a variety of pathological conditions, such as diabetes, cancers and infectious disease. The proposed research will build a new instrument platform to allow high sensitivity identification and high resolution structural characterization of glycans in complex biomatrix.
| Nagy, Gabe; Attah, Isaac K; Garimella, Sandilya V B et al. (2018) Unraveling the isomeric heterogeneity of glycans: ion mobility separations in structures for lossless ion manipulations. Chem Commun (Camb) 54:11701-11704 |
| Zheng, Xueyun; Zhang, Xing; Schocker, Nathaniel S et al. (2017) Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses. Anal Bioanal Chem 409:467-476 |
| Guo, Xuejiang; Fillmore, Thomas L; Gao, Yuqian et al. (2016) Capillary Electrophoresis-Nanoelectrospray Ionization-Selected Reaction Monitoring Mass Spectrometry via a True Sheathless Metal-Coated Emitter Interface for Robust and High-Sensitivity Sample Quantification. Anal Chem 88:4418-25 |
