Protein Biomarker Quantification by Immunoaffinity Liquid Chromatography-Tandem Mass Spectrometry: Current State and Future Vision
Protein Biomarker Quantification by Immunoaffinity Liquid Chromatography-Tandem Mass Spectrometry: Current State and Future Vision
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DOI：
10.1093/clinchem/hvz022
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发表时间：
2020-02-01
影响因子：
9.3
通讯作者：
Ackermann, Bradley L.
中科院分区：
文献类型：
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作者：
Neubert, Hendrik;Shuford, Christopher M.;Ackermann, Bradley L.
免疫亲和-质谱（IA-MS）是一种新兴的分析类型，具有分析和测定蛋白质生物标志物的几个优点。由于IA-MS结合了亲和捕获（类似于配体结合测定（LBA））和质谱（MS）检测，因此该平台通常使用术语混合方法进行描述。本报告的目的是提供IA-MS原理的概述，并通过应用展示该技术的独特力量和潜力。通过将靶免疫亲和富集与使用稳定的同位素标记的内标物和MS检测相结合，IA-MS实现了高灵敏度，同时为液体和组织中蛋白质生物标志物的定量提供了无与伦比的特异性。近年来，IA-MS在制药行业中得到了显著的应用，特别是在临床开发的早期阶段，使以前认为无法实现的生物标志物测量成为可能。相比之下，CLIA实验室采用IA-MS的速度较慢。IA-MS的使用和扩大采用的机会目前的障碍进行了讨论。前进的道路涉及到确定与单独的LBA或MS技术相比，IA-MS是最佳选择的应用程序。IA-MS将继续受益于试剂一代的进步，更灵敏和更高通量的MS技术，以及更广泛的分析社区使用的持续增长。总的来说，对这些机会的追求将确保IA-MS在临床应用中的长期使用。
Immunoaffinity-mass spectrometry (IA-MS) is an emerging analytical genre with several advantages for profiling and determination of protein biomarkers. Because IA-MS combines affinity capture, analogous to ligand binding assays (LBAs), with mass spectrometry (MS) detection, this platform is often described using the term hybrid methods. The purpose of this report is to provide an overview of the principles of IA-MS and to demonstrate, through application, the unique power and potential of this technology. By combining target immunoaffinity enrichment with the use of stable isotope-labeled internal standards and MS detection, IA-MS achieves high sensitivity while providing unparalleled specificity for the quantification of protein biomarkers in fluids and tissues. In recent years, significant uptake of IA-MS has occurred in the pharmaceutical industry, particularly in the early stages of clinical development, enabling biomarker measurement previously considered unattainable. By comparison, IA-MS adoption by CLIA laboratories has occurred more slowly. Current barriers to IA-MS use and opportunities for expanded adoption are discussed. The path forward involves identifying applications for which IA-MS is the best option compared with LBA or MS technologies alone. IA-MS will continue to benefit from advances in reagent generation, more sensitive and higher throughput MS technologies, and continued growth in use by the broader analytical community. Collectively, the pursuit of these opportunities will secure expanded longterm use of IA-MS for clinical applications.