Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, 30332, USA.
Small. 2022 Dec;18(49):e2203309. doi: 10.1002/smll.202203309. Epub 2022 Aug 29.
Inexpensive yet sensitive and specific biomarker detection is a critical bottleneck in diagnostics, monitoring, and surveillance of infectious diseases such as COVID-19. Multiplexed detection of several biomarkers can achieve wider diagnostic applicability, accuracy, and ease-of-use, while reducing cost. Current biomarker detection methods often use enzyme-linked immunosorbent assays (ELISA) with optical detection which offers high sensitivity and specificity. However, this is complex, expensive, and limited to detecting only a single analyte at a time. Here, it is found that biomarker-bound enzyme-labeled probes act synergistically with nanostructured catalytic surfaces and can be used to selectively reduce a soluble silver substrate to generate highly dense and conductive, localized surface silver metallization on microelectrode arrays. This enables a sensitive and quantitative, simple, direct electronic readout of biomarker binding without the use of any intermediate optics. Furthermore, the localized and dry-phase stable nature of the metallization enables multiplexed electronic measurement of several biomarkers from a single drop (<10 µL) of sample on a microchip.This method is applied for the multiplexed point-of-care (POC) quantitative detection of multiple COVID-19 antigen-specific antibodies. Combining a simple microchip and an inexpensive, cellphone-interfaced, portable reader, the detection and discrimination of biomarkers of prior infection versus vaccination is demonstrated.
在诊断、监测和传染病（如 COVID-19）的监控中，经济实惠且具有高灵敏度和特异性的生物标志物检测是一个关键的瓶颈。对多个生物标志物进行多重检测可以实现更广泛的诊断适用性、准确性和易用性，同时降低成本。目前的生物标志物检测方法通常使用酶联免疫吸附测定（ELISA）结合光学检测，具有高灵敏度和特异性。然而，这种方法复杂、昂贵，并且一次只能检测单一分析物。在这里，人们发现与纳米结构的催化表面结合的生物标志物结合的酶标记探针具有协同作用，可以选择性地还原可溶性银基质，在微电极阵列上生成高度密集且导电的局部表面银金属化。这使得无需使用任何中间光学元件，即可对生物标志物结合进行敏感、定量、简单和直接的电子读出。此外，金属化的局部和干相稳定特性允许从微芯片上的单个样本滴（<10 μL）中同时对多个生物标志物进行多重电子测量。该方法已应用于 COVID-19 多种抗原特异性抗体的即时（POC）多重定量检测。该方法结合了简单的微芯片和廉价的、与手机接口的便携式读取器，演示了对先前感染与疫苗接种的生物标志物的检测和区分。
