基于DNA纳米结构的传感界面调控及生物检测应用  

DNA Nanostructure-Based Engineering of the Biosensing Interface for Biomolecular Detection

作　　者：叶德楷 左小磊[1] 樊春海[1] 

机构地区：[1]中国科学院上海应用物理研究所物理生物学研究室上海光源生物成像中心,上海201800

出　　处：《化学进展》2017年第1期36-46,共11页Progress in Chemistry

基　　金：国家自然科学基金项目(No.21422508)资助~~

摘　　要：生物传感技术在环境、安全和医学诊断等应用中具有重要意义。如何精确调控自组装界面上生物识别探针与界面的相互作用来提高生物传感的性能则是其中的关键问题。常规界面组装过程中,DNA等生物分子往往在界面形成非均一的自组装层,分子结合能量壁垒高,识别效率低。我们通过构建有序DNA纳米结构,发展了纳米尺度精确调控界面性质的方法。通过在界面上形成以熵驱动主导的均匀自组装层,增加探针分子间的有效距离,并通过精确调控界面上DNA纳米结构的尺寸,显著提高界面DNA杂交效率与速率。我们在DNA四面体上修饰不同的生物识别分子(DNA、抗体、核酸适配体等),可构建通用检测平台,实现对核酸、蛋白、小分子及细胞的高灵敏检测,并且在复杂样本中同样保持了优异的检测性能。在此基础上,我们将四面体三维结构探针应用于细胞内以及活体检测,研究了DNA四面体在细胞内的运输途径及靶向定位方式,并实现对细胞内ATP分布的传感成像及小鼠体内肿瘤组织的靶向成像,有望发展活体生物传感的新探针。The biosensing technology plays an important role in environmental monitoring,safety control and medical diagnosis.Precise control of the interaction between bio-recognition probe and the interface is critical to improve the sensitivity,specificity and selectivity of biosensors.In a typical bioprobe immobilization,the heterogeneity of self-assembled monolayers on the surface increases the binding energy barrier and decreases the recognition efficiency and rate.We found that DNA nanostructures,such as tetrahedral DNA nanostructures（TDNs）,could increase the homogeneity of self-assembled monolayers via enthalpy-entropy compensation,which enables precise regulation of interfacial property at the nanoscale.By regulating the intermolecular distance of bioprobes,the hybridization efficiency and hybridization rate of DNA probes can be improved significantly.The detection limit of DNA and microRNA can be pushed down to 10 aM limit.The detection limit of antigen detection can be improved to 100 pM and the detection limit of small molecule（cocaine） can be pushed to 33 nM.By using TDNs,we developed a universal detection platform for nucleic acids,proteins,small molecules and cells with superior detection sensitivity.To further use TDN probes in cells and in vivo,we explored the transport pathways of TDNs into the cell and directed their targeting location to specific organelles.We aim to develop DNA nanostructure-based bioprobes for intracellular and in-vivo imaging.

关 键 词：生物传感 界面组装 DNA纳米结构 电化学 细胞成像 

分 类 号：O65[理学—分析化学] O647[理学—化学]