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

 描述（由申请人提供）：聚糖在给定生物过程或致病条件下的特定功能取决于其特定的分子组成和结构。糖组学谱的准确和定量测量可以大大提高我们对聚糖在许多常见健康问题和疾病中所起重要作用的理解。尽管技术进步已经使质谱（MS）成为生物分子分析、明确鉴定和结构表征的重要工具， 由于聚糖的极其复杂的结构和不稳定的性质，在复杂生物基质中的聚糖的分离仍然是基本上具有挑战性的任务。该项目的主要目标是开发一种新的基于离子迁移谱（IMS）/MS的仪器平台，能够检测大的和不稳定的完整聚糖，并以更高的灵敏度和分辨率阐明其结构。新的分析平台将集成一个亚环境压力离子化与纳米电喷雾（SPIN）源，一个回旋离子迁移谱基于无损离子操作（SLIM）技术的结构与高灵敏度飞行时间（TOF）MS通过使用电动离子漏斗接口，以实现超过一个数量级更高的灵敏度和分辨率相比，任何分析工具目前可用于聚糖分析。新的基于SPIN/SLIM的回旋IMS/TOF MS仪器的生物医学应用将通过分析代表不同乳腺癌亚型的不同细胞系中的聚糖来证明，以实现聚糖生物标志物的明确和完整的结构阐明。由此产生的仪器平台预计将具有广泛的生物医学应用，需要高灵敏度和高分辨率的完整聚糖的结构表征。

 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.