基于杂交链式反应和共价有机框架的新型荧光传感器用于ctDNA的高灵敏和选择性检测
A Novel Fluorescent Sensor Based on Hybridization Chain Reaction and Covalent Organic Frameworks for Sensitive and Selective Detection of ctDNA
赵璐 1王涛 1王超宇 1毛佳欣 1刘志雄 1李雅茹 2白云峰 3冯锋1
作者信息
- 1. 山西大同大学化学与化工学院化学生物传感山西省重点实验室 大同 037009
- 2. 山西大同大学农学与生命科学学院 大同 037009
- 3. 山西大同大学化学与化工学院化学生物传感山西省重点实验室 大同 037009;山西大同大学农学与生命科学学院 大同 037009
- 折叠
摘要
共价有机框架是近年来发展起来的一种高度结晶的多孔聚合物,由有机单元连接形成.由于其优异的孔隙率、模块性、结晶性和生物相容性,在传感领域显示出良好的应用前景.本文开发了一种基于杂交链式反应(HCR)和共价有机框架的新型荧光传感平台,用于高灵敏地检测循环肿瘤DNA(ctDNA).ctDNA可以作为HCR的激活剂,通过触发发夹1(H1)和发夹2(H2)的自主交叉打开,激活HCR形成延伸的有缺口的双链DNA,导致荧光信号的变化,从而实现ctDNA的定量检测.HCR产物和荧光信号分别采用琼脂糖凝胶电泳和荧光光谱进行表征.在0~10 nmol/L范围内,ctDNA的浓度与荧光信号呈良好的线性关系,检测限为1.3nmol/L.该方法对ctDNA具有满意的选择性,并在人类血清样品检测中显示出良好的性能.该荧光传感平台为ctDNA的检测提供了新思路,在癌症早期诊断中显示出潜在的应用前景.
Abstract
Covalent organic frameworks connected by organic units are a highly crystalline porous polymer that has been developed in recent years,which show a good application prospect in sensors because of the excellent porosity,modularity,crystallinity and biocompatibility.In this paper,we developed a novel fluorescent sensing platform based on hybridization chain reaction(HCR)and covalent organic frameworks to detect circulating tumor DNA(ctDNA)with high sensitivity.The target ctDNA could serve as the initiator to trigger the autonomous cross-opening of Hairpin 1(Hl)and Hairpin 2(H2)that formed extended nicked double-stranded DNA via HCR,which could result in changes in fluorescence signals,thereby realizing quantitative detection of ctDNA.The HCR products and fluorescence signal response effect were characterized by agarose gel electrophoresis and fluorescence spectroscopy,respectively.In the range of 0~10 nmol/L,the concentration of ctDNA and the fluorescence signal showed a good linear relationship with a detection limit of 1.3 nmol/L.The fluorescent sensing platform had satisfactory selectivity for ctDNA,and showed good performance in human serum samples.This method provided a novel idea for the detection of ctDNA,showing potential application prospects in the early diagnosis of cancer.
关键词
共价有机框架/荧光检测/杂交链式反应/循环肿瘤DNA/传感诊断Key words
Covalent organic framework/Fluorescence detection/HCR/Circulating tumor DNA/Sensing diagnosis引用本文复制引用
基金项目
山西省高等学校科学研究优秀成果培育项目(2020KJ023)
山西省省筹资金资助回国留学人员科研项目(2020-133)
山西省高等学校科技创新项目(2021L368)
山西省高等学校科技创新项目(2022L424)
山西省基础研究计划资助项目(202303021211324)
山西省留学回国人员科技活动择优资助项目(20230036)
大同市应用基础研究项目(2023065)
山西大同大学基础科研基金项目(2022K18)
出版年
2024