Matching sensitivity to abundance: high resolution immuno-mass spectrometry imaging of lanthanide labels and endogenous elements in the murine brain
Matching sensitivity to abundance: high resolution immuno-mass spectrometry imaging of lanthanide labels and endogenous elements in the murine brain
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DOI：
10.1039/c9ja00405j
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发表时间：
2020-04-01
影响因子：
3.4
通讯作者：
Doble, Philip A.
中科院分区：
文献类型：
--
作者：
Clases, David;de Vega, Raquel Gonzalez;Doble, Philip A.
这项工作介绍了一种新的免疫质谱成像方法，通过四极杆为基础的激光烧蚀电感耦合等离子体质谱仪器，是匹配的生物组织中的元素丰度。离子光学和四极质量过滤器参数的操作提供了低水平高质量元素的增加的传输，其通常用作抗体的标记，以高度丰富的内源性低质量元素为代价。过渡金属等中等质量元素的传输仅受到轻微影响。质量分辨率和背景信号的影响进行了严格的讨论和信噪比和成像能力进行了比较，从一个标准的方法。这种新方法导致镧系元素的信噪比提高了6倍，镧系元素通常用作抗体的元素标记，以靶向生物组织中的蛋白质分布。这种信号强度的增加、增强的对比度、检测下限和提高空间分辨率的潜力有助于增强成像和痕量分析，如通过对海马系统和黑质的小鼠脑切片进行成像所证明的。
This work introduces a new method for immuno-mass spectrometry imaging via quadrupole-based laser ablation-inductively coupled plasma-mass spectrometry instruments that is matched to the abundance of elements in biological tissues. Manipulation of ion-optics and quadrupole mass filter parameters provided increased transmission of low level high-mass elements, which are typically used as labels for antibodies, at the expense of highly abundant endogenous low-mass elements. Transmission of mid-mass elements such as transition metals was only slightly affected. The implications for mass resolution and background signals are critically discussed and signal to noise ratios and imaging capabilities are compared to those obtained from a standard method. This novel approach resulted in a 6-fold improved signal to noise ratio for lanthanides that are routinely used as elemental labels for antibodies to target protein distributions in biological tissues. This increase in signal intensity, enhanced contrasts, lower limits of detection and the potential to improve spatial resolution contributed to enhanced imaging and trace analyses, as demonstrated by imaging murine brain sections of the hippocampal system and substantia nigra.