ZnO量子点和SnO2量子点标记抗体结合磁免疫单颗粒电感耦合等离子体质谱法测定人血清中卵巢癌生物标志物CA125和HE4  

ZnO Quantum Dot and SnO2 Quantum Dot Labeling Antibodies and Single Particle Inductively Coupled Plasma Mass Spectrometry Coupled with Magnetic Immunoassay for Detection of Ovarian Cancer Biomarkers CA125 and HE4 in Human Serum

作　　者：曹玉嫔 陈海平 梁洁 邓必阳 CAO Yu-Pin;CHEN Hai-Ping;LIANG Jie;DENG Bi-Yang(Key Laboratory of Traditional Chinese Medicine Extraction and Purification and Quality Analysis,Education Department of Guangxi Zhuang Autonomous Region,College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China;State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources,School of Chemistry and Pharmaceutical Sciences,Guangxi Normal University,Guilin 541004,China)

机构地区：[1]广西中医药大学药学院,广西高校中药提取纯化与质量分析重点实验室,南宁530200 [2]广西师范大学化学与药学学院,省部共建药用资源化学与药物分子工程国家重点实验室,桂林541004

出　　处：《分析化学》2024年第10期1562-1572,共11页Chinese Journal of Analytical Chemistry

基　　金：广西自然科学基金项目(No.2020GXNSFBA159031);国家自然科学基金项目(No.22164004);广西中医药大学第三批“岐黄工程”高层次人才团队培育项目(No.202406)资助。

摘　　要：卵巢癌是致命的妇科恶性肿瘤之一,其生物标志物的含量是一个重要的临床诊断依据。联合检测人血清中糖类抗原125(Carbohydrate antigen 125,CA125)和人附睾分泌蛋白4(Human epididymis protein 4,HE4)可提高卵巢癌的临床诊断准确率。本研究建立了一种氨基功能化的氧化锌量子点(ZnO QD)和二氧化锡量子点(SnO2 QD)标记抗体结合磁免疫单颗粒电感耦合等离子体质谱法分析人血清中卵巢癌生物标志物CA125和HE4的新方法。本方法将氨基功能化的四氧化三铁磁性纳米粒子与CA125和HE4一抗结合,用于捕获CA125和HE4抗原;利用自行合成的ZnO QD和SnO2 QD分别标记CA125和HE4二抗,通过ICP-MS测定Zn和Sn的信号频数从而实现对CA125和HE4的定量分析。在最佳实验条件下,CA125和HE4的线性范围分别为0.02~200 U/mL和0.02~100 ng/mL,检出限(3σ)分别为0.004 U/mL和0.006 ng/mL,相对标准偏差(RSD)分别为2.2%和3.5%(n=6)。本方法具有灵敏度高、选择性好和试剂消耗少等优点,已成功用于人血清中CA125和HE4含量的测定。Ovarian cancer is one of the most fatal of all the gynecological malignancies.The detection of biomarker is one of the diagnostic bases for the disease.The combined detection of carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)in human serum can improve the accuracy of clinical diagnosis for ovarian cancer.In this study,a new method for analysis of ovarian cancer biomarkers CA125 and HE4 in human serum using zinc oxide quantum dot(ZnO QD)and tin oxide quantum dot(SnO2 QD)labeled antibodies coupled with single particle inductively coupled plasma mass spectrometry(ICP-MS)was developed.CA125 and HE4 antigens were captured by amino-modified magnetic nanoparticles combined with CA125 and HE4 primary antibodies.CA125 and HE4 secondary antibodies were labeled by ZnO QD and SnO2 QD,respectively.The signal frequency of Zn and Sn was determined by ICP-MS to realize the quantitative analysis of CA125 and HE4.The linear detection ranges of CA125 and HE4 were 0.02–200 U/mL and 0.02–100 ng/mL,the detection limits were 0.004 U/mL and 0.006 ng/mL(3σ),and the RSDs were 2.2%and 3.5%(n=6),respectively.This method had many advantages such as high sensitivity,good selectivity and less reagent consumption,and was successfully applied to determine the content of CA125 and HE4 in human serum.

关 键 词：氧化锌量子点 二氧化锡量子点 糖类抗原125 人附睾分泌蛋白4 电感耦合等离子体质谱 单颗粒分析 

分 类 号：R737.31[医药卫生—肿瘤]