Fletcher John S, Rabbani Sadia, Henderson Alex, Blenkinsopp Paul, Thompson Steve P, Lockyer Nicholas P, Vickerman John C
Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester, UK.
Anal Chem. 2008 Dec 1;80(23):9058-64. doi: 10.1021/ac8015278.
Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has unique capabilities in the area of high-resolution mass spectrometric imaging of biological samples. The technique offers parallel detection of native and non-native molecules at physiological concentrations with potentially submicrometer spatial resolution. Recent advances in SIMS technology have been focused on generating new ion sources that can in turn be used to eject more intact molecular and biological characteristic species from a sample. The introduction of polyatomic ion beams, particularly C60, for TOF-SIMS analysis has created a whole new application of molecular depth profiling and 3D molecular imaging. However, such analyses, particularly at high lateral resolution, are severely hampered by the accompanying mass spectrometry associated with current TOF-SIMS instruments. Hence, we have developed an instrument that overcomes many of the drawbacks of current TOF-SIMS spectrometers by removing the need to pulse the primary ion beam. The instrument samples the secondary ions using a buncher that feeds into a specially designed time-of-flight analyzer. We have validated this new instrumental concept by analyzing a number of biological samples generating 2D and 3D images showing molecular localization on a subcellular scale, over a practical time frame, while maintaining high mass resolution. We also demonstrate large area mapping and the MS/MS capability of the instrument.
飞行时间二次离子质谱（TOF-SIMS）在生物样品的高分辨率质谱成像领域具有独特的能力。该技术能够在生理浓度下对天然和非天然分子进行并行检测，潜在空间分辨率可达亚微米级。二次离子质谱（SIMS）技术的最新进展集中在开发新的离子源，这些离子源可用于从样品中喷射出更多完整的分子和生物特征物种。将多原子离子束，特别是C60，引入TOF-SIMS分析，开创了分子深度剖析和三维分子成像的全新应用。然而，此类分析，尤其是在高横向分辨率下，受到当前TOF-SIMS仪器所伴随的质谱分析的严重阻碍。因此，我们开发了一种仪器，通过消除对初级离子束进行脉冲处理的需求，克服了当前TOF-SIMS光谱仪的许多缺点。该仪器使用一个聚束器对二次离子进行采样，聚束器将离子送入专门设计的飞行时间分析仪。我们通过分析多个生物样品验证了这一新的仪器概念，这些样品生成了二维和三维图像，显示了在实际时间范围内亚细胞尺度上的分子定位，同时保持了高质量分辨率。我们还展示了该仪器的大面积测绘和串联质谱（MS/MS）能力。
