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Multiomics Imaging Using High-Energy Water Gas Cluster Ion Beam Secondary Ion Mass Spectrometry [(H2O)n-GCIB-SIMS] of Frozen-Hydrated Cells and Tissue
Analytical Chemistry ( IF 6.7 ) Pub Date : 2021-05-26 , DOI: 10.1021/acs.analchem.0c05210
Hua Tian 1 , Sadia Sheraz Née Rabbani 2 , John C Vickerman 3 , Nicholas Winograd 1
Affiliation  

Integration of multiomics at the single-cell level allows the unambiguous dissecting of phenotypic heterogeneity at different states such as health, disease, and biomedical response. Imaging mass spectrometry holds the promise of being able to measure multiple types of biomolecules in parallel in the same cell. We have explored the possibility of using water gas cluster ion beam secondary ion mass spectrometry [(H2O)n-GCIB-SIMS] as an analytical tool for multiomics assay. (H2O)n-GCIB has been hailed as an ideal ionization source for biological sampling owing to the enhanced chemical sensitivity and reduced matrix effect. Taking advantage of 1 μm spatial resolution by using a high-energy beam system, we have clearly shown the enhancement of multiple intact biomolecules up to a few hundredfold in single cells. Coupled with the cryogenic sample preparation/measurement, the lipids and metabolites were imaged simultaneously within the cellular region, uncovering the pristine chemistry for integrated omics in the same sample. We have demonstrated that double-charged myelin protein fragments and single-charged multiple lipids and metabolites can be localized in the same cells/tissue with a single acquisition. Our exploration has also been extended to the capability of (H2O)n-GCIB in the generation of multiple charged peptides on protein standards. Frozen hydration combined with (H2O)n-GCIB provides the possibility of universal enhancement for the ionization of multiple bio-molecules, including peptides/proteins which has allowed “omics” to become feasible in the same sample using SIMS.

中文翻译:


使用高能水气簇离子束二次离子质谱 [(H2O)n-GCIB-SIMS] 对冷冻水合细胞和组织进行多组学成像



单细胞水平上的多组学整合可以明确剖析健康、疾病和生物医学反应等不同状态下的表型异质性。成像质谱有望能够在同一细胞中并行测量多种类型的生物分子。我们探索了使用水气团簇离子束二次离子质谱[(H 2 O) n -GCIB-SIMS]作为多组学分析分析工具的可能性。 (H 2 O) n -GCIB因其增强的化学灵敏度和减少的基质效应而被誉为生物采样的理想电离源。通过使用高能光束系统,利用 1 μm 的空间分辨率,我们清楚地展示了单个细胞中多个完整生物分子的增强高达数百倍。与低温样品制备/测量相结合,脂质和代谢物在细胞区域内同时成像,揭示了同一样品中整合组学的原始化学成分。我们已经证明,双电荷髓鞘蛋白片段和单电荷多种脂质和代谢物可以通过单次采集定位在相同的细胞/组织中。我们的探索还扩展到 (H 2 O) n -GCIB 在蛋白质标准品上生成多个带电肽的能力。冷冻水合与 (H 2 O) n -GCIB 相结合,为多种生物分子(包括肽/蛋白质)的电离提供了普遍增强的可能性,这使得使用 SIMS 在同一样品中实现“组学”变得可行。
更新日期:2021-06-08
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