Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media.
Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media.
复制标题
用于复杂介质中小分子分析物连续光学检测的模块化适体开关。
DOI：
10.1002/adma.202304410
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Digonnet,MichelJF
中科院分区：
文献类型：
--
作者：
Hariri,AmaniA;Cartwright,AlyssaP;Dory,Constantin;Gidi,Yasser;Yee,Steven;Thompson,IanAP;Fu,KaiyuX;Yang,Kiyoul;Wu,Diana;Maganzini,Nicolò;Feagin,Trevor;Young,BrianE;Afshar,BehradHabib;Eisenstein,Michael;Digonnet,MichelJF
适体是一类很有前途的亲和试剂，因为信号转导机制可以内置到试剂中，这样它们就可以在靶标结合时直接产生物理可测量的输出信号。然而，将信号转导功能赋予适体仍然是一个反复试验的过程，可能会损害其亲和力或特异性，并且通常需要配体结合域或其结构的知识。在这项工作中，描述了一种设计架构，可以将现有适体转换为“可逆适体开关”，其动力学和热力学性质可以在不了解配体结合域或其结构的先验知识的情况下进行调整。最后，通过将这些适体开关与基于倏逝场的光学检测硬件相结合，最大限度地减少样品自发荧光，本研究展示了第一个光学生物传感器系统，可以连续测量复杂样品（人工脑脊液和未稀释血浆）中的多种生物标志物（多巴胺和皮质醇），在生理相关浓度范围内具有秒级和亚秒级时间响应。
Aptamers are a promising class of affinity reagents because signal transduction mechanisms can be built into the reagent, so that they can directly produce a physically measurable output signal upon target binding. However, endowing the signal transduction functionality into an aptamer remains a trial‐and‐error process that can compromise its affinity or specificity and typically requires knowledge of the ligand binding domain or its structure. In this work, a design architecture that can convert an existing aptamer into a “reversible aptamer switch” whose kinetic and thermodynamic properties can be tuned without a priori knowledge of the ligand binding domain or its structure is described. Finally, by combining these aptamer switches with evanescent‐field‐based optical detection hardware that minimizes sample autofluorescence, this study demonstrates the first optical biosensor system that can continuously measure multiple biomarkers (dopamine and cortisol) in complex samples (artificial cerebrospinal fluid and undiluted plasma) with second and subsecond‐scale time responses at physiologically relevant concentration ranges.