Automation of Biomarker Preconcentration, Capture, and Nanozyme Signal Enhancement on Paper-Based Devices
Automation of Biomarker Preconcentration, Capture, and Nanozyme Signal Enhancement on Paper-Based Devices
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DOI：
10.1021/acs.analchem.9b03105
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发表时间：
2019-09-17
影响因子：
7.4
通讯作者：
Kamei, Daniel T.
中科院分区：
文献类型：
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作者：
Bradbury, Daniel W.;Azimi, Milad;Kamei, Daniel T.
传染病仍然是发展中国家死亡的主要原因之一，因为缺乏基本的卫生设施、医疗诊所和集中实验室。基于纸的快速诊断测试，例如侧流免疫测定（LFA），提供了传统的基于实验室的测试的有希望的替代方案;然而，它们通常具有差的灵敏度。生物标记物预富集和信号增强是提高纸基检测灵敏度的两种常用方法。虽然有效，但这些方法通常需要多个液体处理步骤，这对于未经训练的人员在护理点环境中使用并不理想。我们的实验室以前发现了在纸上分离的水两相系统（ATPS）的现象，这使得LFA上的生物标志物的浓缩和检测能够无缝集成。在这项工作中，我们扩展了ATPS纸上分离的功能，除了浓缩生物标志物外，还可以自动顺序递送信号增强试剂。通过改变ATPS的初始组成来控制试剂递送的时间。我们应用这项技术来自动化LFA上的生物标志物浓度和纳米酶信号增强，在检测大肠杆菌时，检测限比传统LFA提高了30倍，同时保持了单一的应用步骤。
Infectious diseases remain one of the leading causes of deaths in developing countries because of a lack of basic sanitation, healthcare clinics, and centralized laboratories. Paper-based rapid diagnostic tests, such as the lateral-flow immunoassay (LFA), provide a promising alternative to the traditional laboratory-based tests; however, they typically suffer from having a poor sensitivity. Biomarker preconcentration and signal enhancement are two common methods to improve the sensitivity of paper-based assays. While effective, these methods often require multiple liquid handling steps which are not ideal for use by untrained personnel in a point-of-care setting. Our lab previously discovered the phenomenon of an aqueous two-phase system (ATPS) separating on paper, which allowed for the seamless integration of concentration and detection of biomarkers on the LFA. In this work, we have extended the functionality of an ATPS separating on paper to automate the sequential delivery of signal enhancement reagents in addition to concentrating biomarkers. The timing of reagent delivery was controlled by changing the initial composition of the ATPS. We applied this technology to automate biomarker concentration and nanozyme signal enhancement on the LFA, resulting in a 30-fold improvement in detection limit over the conventional LFA when detecting Escherichia coli, all while maintaining a single application step.