质谱在检测生物分子方面有很大潜力，但现有方法存在几个缺陷，包括缺少所需的灵敏度和需要基质分子促使分析对象发生离子化等。一种利用激光或离子束来从纳米尺度的小囊中气化材料的全新方法有可能克服这些局限性。该方法涉及一种特制的表面，它含有“启动分子”，这些“启动分子”在受到激光或离子束照射时会猛烈爆发，这种爆发释放出离子化的分析物分子被吸收到表面上，使其能被检测到。被称为纳米结构启动质谱（NIMS）的这一方法，能以极高的灵敏度分析非常小的区域，从而允许对肽阵列、血液、尿和单个细胞进行分析，甚至能用于组织成像。
原始出处:
Nature 449, 1033-1036 (25 October 2007) | doi:10.1038/nature06195; Received 3 August 2007; Accepted 23 August 2007
Clathrate nanostructures for mass spectrometry
Trent R. Northen1,2,6, Oscar Yanes1,2,6, Michael T. Northen4, Dena Marrinucci3, Winnie Uritboonthai1,2, Junefredo Apon1,2, Stephen L. Golledge5, Anders Nordström1,2 & Gary Siuzdak1,2,6
Department of Molecular Biology,
Scripps Center for Mass Spectrometry,
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Materials Department, University of California at Santa Barbara, Santa Barbara, California 93106, USA
CAMCOR Surface Analysis Facility at the University of Oregon, Eugene, Oregon 97403, USA
These authors contributed equally to this work.
Correspondence to: Gary Siuzdak1,2,6 Correspondence and requests for materials should be addressed to G.S. (Email: siuzdak@scripps.edu).
The ability of mass spectrometry to generate intact biomolecular ions efficiently in the gas phase has led to its widespread application in metabolomics1, proteomics2, biological imaging3, biomarker discovery4 and clinical assays (namely neonatal screens5). Matrix-assisted laser desorption/ionization6, 7 (MALDI) and electrospray ionization8 have been at the forefront of these developments. However, matrix application complicates the use of MALDI for cellular, tissue, biofluid and microarray analysis and can limit the spatial resolution because of the matrix crystal size9 (typically more than 10 m), sensitivity and detection of small compounds (less than 500 Da). Secondary-ion mass spectrometry10 has extremely high lateral resolution (100 nm) and has found biological applications11, 12 although the energetic desorption/ionization is a limitation owing to molecular fragmentation. Here we introduce nanostructure-initiator mass spectrometry (NIMS), a tool for spatially defined mass analysis. NIMS uses 'initiator' molecules trapped in nanostructured surfaces or 'clathrates' to release and ionize intact molecules adsorbed on the surface. This surface responds to both ion and laser irradiation. The lateral resolution (ion-NIMS about 150 nm), sensitivity, matrix-free and reduced fragmentation of NIMS allows direct characterization of peptide microarrays, direct mass analysis of single cells, tissue imaging, and direct characterization of blood and urine.
