基于少层MoS_(2)纳米片的光学生物传感器用于癌症标志物ctDNA的检测  

An Optical Biosensor Based on Few-Layer MoS_(2)Nanosheets for Sensitive Detection of Tumor Marker ctDNA

作　　者：卫瑚玥 李杜娟 崔治莲 樊凯 杨伟煌 刘红英 李丽丽 吴薇[1,2] 王高峰[1,2] Wei Huyue;Li Dujuan;Cui Zhilian;Fan Kai;Yang Weihuang;Liu Hongying;Li Lili;Wu Wei;Wang Gaofeng(College of Electronic Information,Hangzhou Dianzi University,Hangzhou 310018,China;Small Microsensor and Microsystem Engineering Research Center of Ministry of Education,Hangzhou 310018,China;School of Automation,Hangzhou Dianzi University,Hangzhou 310018,China)

机构地区：[1]杭州电子科技大学电子信息学院,杭州310018 [2]智能微传感器与微系统教育部工程研究中心,杭州310018 [3]杭州电子科技大学自动化学院,杭州310018

出　　处：《中国生物医学工程学报》2024年第2期183-195,共13页Chinese Journal of Biomedical Engineering

基　　金：浙江省自然科学基金(LY24F010008);国家自然科学基金重大研究计划重点项目(92373202);国家自然科学基金专项研究重点项目(62141409)。

摘　　要：癌症已成为威胁人类健康和生命的主要疾病之一。循环肿瘤DNA(ctDNA)检测作为一种实用的液体活检技术,在肿瘤诊断、靶向治疗和预后预测中具有重要的应用前景。因此,本课题研究了一种基于少层MoS_(2)纳米片的光学生物传感器用于癌症标志物ctDNA的高灵敏检测。首先,采用剪切剥离法制备少层MoS_(2)纳米片,并对制备条件进行优化,以制备横向尺寸较大、厚度均匀的少层MoS_(2)纳米片;其次,通过分散液吸光度的变化研究少层MoS_(2)纳米片在高浓度盐溶液中的加速聚集沉淀行为;然后,基于MoS_(2)纳米片对单链DNA的吸附力,研究了单链DNA对于盐诱导沉淀少层MoS_(2)纳米片的抑制作用;最后,利用杂交形成的双链DNA从少层MoS_(2)纳米片上脱落而导致的分散液吸光度的变化构建光学生物传感器,并通过cpDNA与不同浓度的ctDNA杂交对该传感器的性能进行检测。结果表明,当cpDNA浓度为100 nM时,浓度范围在25~100 nM的ctDNA与少层MoS_(2)纳米片分散液的吸光度呈反比线性关系。在401和448 nm波长处时,少层MoS_(2)纳米片分散液的吸光度与ctDNA浓度的线性回归方程分别为Y=0.23557-0.00070X,R^(2)=0.94222和Y=0.21253-0.00050X,R^(2)=0.95141。所构建的光学生物传感器成功地实现了对癌症标志物ctDNA的检测;为未来的体外癌症检测和诊断提供了一种有效的传感策略。Cancer has become one of the major diseases threatening human health and life.Circulating tumor DNA(ctDNA)testing,as a practical liquid biopsy technique,is a promising method for cancer diagnosis,targeted therapy and prognosis.In this work,an optical biosensor based on few-layer MoS_(2)nanosheets was studied for the highly sensitive detection of tumor marker ctDNA.Firstly,The few-layer MoS_(2)nanosheets were prepared by shear exfoliation method,and the preparation conditions were optimized to prepare the few-layer MoS_(2)nanosheets with large transverse size and uniform thickness.Secondly,the accelerated aggregation and precipitation behavior of MoS_(2)nanosheets in high concentration salt solution was studied by detecting the absorbance change of dispersion.Then,based on the adsorption capacity of MoS_(2)nanosheets on single-stranded DNA,the inhibition effect of single-stranded DNA on salt-induced precipitation of few-layer MoS_(2)nanosheets was studied.Finally,the optical biosensor was constructed by using the change of absorbance of dispersion caused by the fall off of double-stranded DNA formed by hybridization from the few-layer MoS_(2)nanosheets,and the performance of the sensor was tested by hybridizing cpDNA with different concentrations of ctDNA.Results showed that the absorbance of ctDNA in the concentration range of 25 nM-100 nM was inversely linear with the dispersion of MoS_(2)nanosheets when cpDNA concentration was 100 nM.The linear regression equations between the absorbance of the dispersion of few-layer MoS_(2)nanosheets and the ctDNA concentration at wavelengths of 401 nm and 448 nm were Y=0.23557-0.00070X,R^(2)=0.94222 and Y=0.21253-0.00050X,R^(2)=0.95141,respectively.This study demonstrated that the optical biosensor was able to detect tumor marker ctDNA and provided an effective sensing strategy for future in vitro cancer detection and diagnosis.

关 键 词：少层MoS_(2)纳米片 CTDNA 生物传感器 紫外光谱 

分 类 号：R318[医药卫生—生物医学工程]