A hybrid IMS-MS platform for ultrasensitive and high resolution glycan analysis

 描述(申请人提供)：在特定的生物过程或致病条件下，葡聚糖的特定功能取决于其特定的分子组成和结构。糖组分的准确和定量测量可以极大地提高我们对多糖在许多常见健康问题和疾病中所起的重要作用的理解。尽管技术的进步使质谱仪(MS)成为生物分子分析的基本工具，但明确的鉴定和结构表征 由于葡聚糖极其复杂的结构和不稳定的性质，在复杂的生物基质中提取葡聚糖仍然是最具挑战性的主要任务。该项目的主要目标是开发一种新的基于离子迁移率光谱(IMS)/MS的仪器平台，能够检测大而不稳定的完整多糖，并以更高的灵敏度和分辨率阐明其结构。新的分析平台将亚常压电离与纳米电喷雾(SPIN)源集成在一起，纳米电喷雾(SPIN)源是一种基于无损离子操纵(SLIM)技术结构的回旋IMS，通过使用电动离子漏斗接口实现高灵敏度的飞行时间(TOF)MS，与目前可用于多糖分析的任何分析工具相比，灵敏度和分辨率都提高了一个数量级以上。新的基于SPIN/SLIM的回旋加速器IMS/TOF MS仪器将通过分析代表不同乳腺癌亚型的不同细胞系中的糖链来展示其生物医学应用，以实现对糖链生物标记物的明确和完整的结构阐明。由此产生的仪器平台有望具有广泛的生物医学应用，需要完整的多糖的高灵敏度和高分辨率的结构表征。

 DESCRIPTION (provided by applicant): 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.