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首页> 外文期刊>Journal of mass spectrometry: JMS >Laser secondary neutral mass spectrometry for copper detection in micro-scale biopsies
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Laser secondary neutral mass spectrometry for copper detection in micro-scale biopsies

机译：激光二次中性质谱法用于微型活检中的铜检测

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摘要

Disease progression and clinical diagnostics of a number of hereditable metabolic diseases are determined by organ involvement in disturbed deposition of certain molecules. Current clinical imaging is unable to visualize this maldistribution with sufficient specificity and sensitivity, such as in Wilson's disease. The quest for understanding cellular Cu distribution in these patients requires element- and molecule-specific images with nanometer-scale spatial resolution. We have used a new cryo-mass spectrometric instrument with an integrated cryosectioning chamber for preparation and analysis of frozen hydrated samples of Wilson's disease tissue. With laser post-ionization secondary neutral mass spectrometry (laser-SNMS), we were able to image Cu and other intrinsic elements and molecules in less than 1 mg of frozen hydrated liver tissue from a murine model of Wilson's disease. A 40-50 times higher Cu concentration was measured in the disease tissue as compared to the control mouse. Furthermore, major histomorphological changes were observed using this advanced nano-science tool. The results showed that the combination of in-vacuum cryosectioning and cryo-laser-SNMS technologies is particularly well suited for identifying specific cell structures and imaging trace element concentrations with subcellular resolution and upper-parts-per-billion sensitivity in biological samples. This technology can provide a novel diagnostic tool for clinical applications in various diseases involving trace elements.
机译：许多可遗传代谢疾病的疾病进展和临床诊断取决于器官参与某些分子沉积紊乱的情况。当前的临床成像不能以足够的特异性和敏感性来可视化这种分布不均，例如在威尔逊氏病中。为了了解这些患者中细胞铜的分布，需要具有纳米级空间分辨率的特定于元素和分子的图像。我们已经使用了带有一体式冷冻切片室的新型冷冻质谱仪，用于制备和分析威尔逊病组织的冷冻水合样品。使用激光电离二次中性质谱法（laser-SNMS），我们能够对威尔逊氏病小鼠模型中少于1 mg的冷冻水合肝组织中的Cu和其他固有元素和分子进行成像。与对照小鼠相比，在疾病组织中测得的铜浓度高40-50倍。此外，使用这种先进的纳米科学工具观察到主要的组织形态学变化。结果表明，真空冷冻切片和冷冻激光SNMS技术的结合特别适合于鉴定特定的细胞结构，并在生物样品中以亚细胞分辨率和十亿分之几的灵敏度对微量元素浓度进行成像。该技术可以为涉及微量元素的各种疾病的临床应用提供新颖的诊断工具。

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