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四极杆-线形离子阱串联质谱系统及临床生物标志物分析
Xiang Fang, Jie Xie, Shiying Chu, You Jiang, Yuting An, Chang Li, Xiaoyun Gong, Rui Zhai, Zejian Huang, Chunling Qiu, Xinhua Dai
工程（英文） ›› 2022, Vol. 16 ›› Issue (9) : 56-64.
PDF(2749 KB)
PDF(2749 KB)
四极杆-线形离子阱串联质谱系统及临床生物标志物分析
Quadrupole-Linear Ion Trap Tandem Mass Spectrometry System for Clinical Biomarker Analysis
确高效测量小分子疾病标志物对临床诊断具有重要意义。本研究自主研制了四极杆-线形离子阱（quadrupole-linear ion trap, Q-LIT）串联质谱仪。四极杆筛选目标母离子，线形离子阱同时注入、捕获和碎裂，有效降低空间电荷效应，富集目标子离子，提升灵敏度。采用电喷雾离子源（electrospray ionization, ESI），选择反应监测和正离子扫描模式。质量范围为m/z 195~2022。当m/z 达2000，且扫描速度为1218 amu·s−1时，单位分辨率和准确度均优于m/z 0.28。碰撞诱导解离（collision-induced dissociation, CID）由共振激发，其无量纲马修参数q值为0.40。激发50 ms，CID效率达64%。胍基乙酸（guanidinoacetic acid, GAA）和肌酸（creatine, CRE）作为小分子临床生物标志物的模型化合物。GAA和CRE定量限分别为1.0 nmol·L−1和0.2 nmol·L−1。自主研制ESI-Q-LIT串联质谱仪成功分析了77例实际样本。该方法可以削减基质效应，降低空间电荷效应，避免色谱分离，简化前处理过程。新型Q-LIT串联质谱系统有望成为临床诊疗中生物标志物测定的新选择。
The accurate and efficient measurement of small molecule disease markers for clinical diagnosis is of great importance. In this study, a quadrupole-linear ion trap (Q-LIT) tandem mass spectrometer was designed and built in our laboratory. Target precursor ions were first selected in the quadrupole, and then injected, trapped, and fragmented simultaneously in the linear ion trap (LIT) to reduce the space charge effect, enrich the target product ions, and promote sensitivity. The targeted analytes were measured with selected reaction monitoring using a positive scan mode with electrospray ionization (ESI). Ions with a mass-to-charge ratio (m/z) ranging from 195 to 2022 were demonstrated. When scanning at 1218 amu•s−1, unit resolution and an accuracy of higher than m/z 0.28 was obtained for m/z up to 2000. The dimensionless Mathieu parameter (q) value used in this study was 0.40 for collision-induced dissociation (CID), which was activated by resonance excitation. And an overall CID efficiency of 64% was achieved (activation time, 50 ms). Guanidinoacetic acid (GAA) and creatine (CRE) were used as model compounds for small molecule clinical biomarkers. The limits of quantification were 1.0 and 0.2 nmol•L−1 for GAA and CRE, respectively. A total of 77 actual samples were successfully analyzed by the home-built ESI-Q-LIT tandem mass spectrometry system. The developed method can reduce matrix interference, minimize space charge effects, and avoid the chromatographic separation of complex samples to simplify the pretreatment process. This novel Q-LIT system is expected to be a good candidate for the determination of biomarkers in clinical diagnosis and therapeutics.
线形离子阱 / 四极杆 / 空间电荷效应 / 碰撞诱导解离 生物标志物 /
Linear ion trap / Quadrupole / Space charge effect Collision-induced dissociation / Biomarker
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