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首页> 外文期刊>Mass Spectrometry Letters >Dynamic MRM Measurements of Multi-Biomarker Proteins by Triple-Quadrupole Mass Spectrometry with Nanoflow HPLC-Microfluidics Chip
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Dynamic MRM Measurements of Multi-Biomarker Proteins by Triple-Quadrupole Mass Spectrometry with Nanoflow HPLC-Microfluidics Chip

机译：纳米流HPLC-微流控芯片通过三重四极杆质谱对多生物标志物蛋白质进行动态MRM测定

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The development of clinical biomarkers involves discovery, verification, and validation. Recently, multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (IDMS) has shown considerable promise for the direct quantification of proteins in clinical samples. In particular, multiple biomarkers have been tracked in a single experiment using MRM-based MS approaches combined with liquid chromatography. We report here a highly reproducible, quantitative, and dynamic MRM system for validating multi-biomarker proteins using Nanoflow HPLC-Microfluidics Chip/Triple-Quadrupole MS. In this system, transitions were acquired only during the retention window of each eluting peptide. Transitions with the highest MRM-MS intensities for the five target peptides from colon cancer biomarker candidates were automatically selected using Optimizer software. Relative to the corresponding non-dynamic system, the dynamic MRM provided significantly improved coefficients of variation in experiments with large numbers of transitions. Linear responses were obtained with concentrations ranging from fmol to pmol for five target peptides.
机译：临床生物标志物的开发涉及发现，验证和确认。最近，多反应监测（MRM）与稳定同位素稀释质谱法（IDMS）结合使用已显示出对临床样品中蛋白质的直接定量分析的巨大希望。特别是，使用基于MRM的MS方法与液相色谱相结合的单个实验已跟踪了多个生物标记。我们在这里报告了一种高度可重复，定量和动态的MRM系统，用于使用Nanoflow HPLC-Microfluidics芯片/ Triple-Quadrupole MS验证多种生物标志物蛋白。在该系统中，仅在每种洗脱肽的保留窗口内获得过渡。使用Optimizer软件自动选择来自结肠癌生物标志物候选物的五个靶标肽具有最高MRM-MS强度的转变。相对于相应的非动态系统，动态MRM在具有大量过渡的实验中提供了显着改善的变异系数。对于五个目标肽，线性响应的浓度范围为fmol至pmol。

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