We report a means by which atomic and molecular secondary ions, including cholesterol and fatty acids, can be sputtered through single-layer graphene to enable secondary ion mass spectrometry (SIMS) imaging of untreated wet cell membranes in solution at subcellular spatial resolution. We can observe the intrinsic molecular distribution of lipids, such as cholesterol, phosphoethanolamine and various fatty acids, in untreated wet cell membranes without any labeling. We show that graphene-covered cells prepared on a wet substrate with a cell culture medium reservoir are alive and that their cellular membranes do not disintegrate during SIMS imaging in an ultra-high-vacuum environment. Ab initio molecular dynamics calculations and ion dose-dependence studies suggest that sputtering through single-layer graphene occurs through a transient hole generated in the graphene layer. Cholesterol imaging shows that methyl-β-cyclodextrin preferentially extracts cholesterol molecules from the cholesterol-enriched regions in cell membranes.

我们报告了一种方法，可以通过单层石墨烯溅射原子和分子二次离子（包括胆固醇和脂肪酸），从而以亚细胞空间分辨率对溶液中未处理的湿细胞膜进行二次离子质谱 (SIMS) 成像。我们可以在未处理的湿细胞膜中观察到脂质的内在分子分布，例如胆固醇、磷酸乙醇胺和各种脂肪酸，而无需任何标记。我们表明，在具有细胞培养基储存器的湿基板上制备的石墨烯覆盖的细胞是活的，并且它们的细胞膜在超高真空环境中的 SIMS 成像过程中不会分解。从头算分子动力学计算和离子剂量依赖性研究表明，通过单层石墨烯的溅射是通过石墨烯层中产生的瞬态空穴发生的。胆固醇成像显示甲基-β-环糊精优先从细胞膜中富含胆固醇的区域提取胆固醇分子。