多靶标平行识别微流控芯片用于即时检测

The growing trend of chronic noncommunicable diseases has become a serious threat to the health of Chinese residents, causing a huge challenge for the health care system. For improving the situation of inadequate medical resources in China, the household point-of-care detection platform can be widely developed to achieve higher diagnostic efficiency and better medical experience of patients. Due to the urgent requirement in point-of-care, this project will propose a novel enzyme-mediated approach integrated with the versatile aptasensing mechanism for signal transduction and amplification, ultimately establishing a multiplexed target-responsive platform for visual quantitative detection. Based on the self-driven flow and the visualization of distance signal from the paper-based microfluidic technology, the instrument-free quantitative readout can be achieved by the naked eye with simplified chip operation in the whole process. Through a flexible regulation of multiple aptasensors on the composite microchip, various analytes related to chronic disease enable to be simultaneously quantified by the portable in vitro detection. .The project will be focused on the following aspects: (1) Signal-transduction mechanism: enzyme-mediated signal transduction and amplification, (2) Chip construction: design and fabrication of multiplexed composite microchip, (3) On-chip application: enzyme-mediated aptasensor integrated quantitative distance readout, (4) Development of multiplexed microchip: simultaneous parallel detection of multiple targets in complex biomatrix.

不断增长的慢性病发展趋势严重威胁着中国居民的健康，给卫生医疗系统带来了巨大的挑战。通过构建家用级便携式即时检测平台，可以有效缓解医疗资源紧缺的压力，提高慢性病患者的诊断效率和就医体验。基于迫切的应用需求，本项目拟开发一种酶介导信号转化与放大新策略，兼容核酸适配体传感的通用机制实现芯片集成化，最终建立多靶标平行识别的可视化定量检测新平台。基于纸基微流控技术的自驱动导流与移动距离可视化，全流程一体化芯片操作，无需仪器辅助即可完成裸眼定量读取。可控负载核酸适配体传感群于复合微芯片上，对慢性病相关的多种待测物实现同时的便携式体外定量检测。.项目拟重点研究以下内容：(1) 信号转导机理探究：酶介导信号转化与放大的新方法；(2) 芯片构筑：多通路复合材料微芯片的设计制作；(3) 集成芯片应用：酶介导核酸适配体传感器集成化的距离定量读取；(4) 多重识别微芯片的开发：实际样品中多靶标的同时平行检测。

鉴于慢性病的长期监测需求，通用可靠的便携式即时检测微流控芯片平台提供了高效稳定的诊断支持。本项目针对传统检测手段对大型仪器和繁琐操作的依赖，提出了信标（由酶拓展至纳米仿生酶等信号转导材料）介导信号转化与放大新方法，兼容了酶促反应、核酸识别、免疫识别等通用机制，并实现了便携简易的微流控芯片集成化。对天然酶与纳米仿生酶的快速催化机制进行了系统性研究，组装了纸基、聚合物、及复合材料的多功能微流控芯片，构建了多种信标介导可视化传感的微流控芯片平台用于疾病标志物的即时检测。主要完成工作包括（1）系统性地研究了天然酶与纳米仿生酶的快速催化性能并筛选了即时检测中的最优反应条件；（2）根据信标催化特性构建了一系列多功能复合材料微流控芯片；（3）深入探索了微流控芯片中信标介导可视化传感机理，揭示了疾病标志物与不同可视化信号的特异性关系；（4）开发了多种高通量、多靶标可视化即时检测微流控芯片，适用于小分子、氨基酸、核酸、免疫抗体等多类别疾病标志物的便携检测应用。