Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.
Shenzhen Bay Laboratory, No. 9 Duxue Road, Shenzhen 518055, China.
ACS Nano. 2022 Jan 25;16(1):180-191. doi: 10.1021/acsnano.1c05267. Epub 2022 Jan 11.
As a typical, classical, but powerful biochemical sensing technology in analytical chemistry, enzyme-linked immunosorbent assay (ELISA) shows excellence and wide practicability for quantifying analytes of ultralow concentration. However, long incubation time and burdensome laborious multistep washing processes make it inefficient and labor-intensive for conventional ELISA. Here, we propose rod-like magnetically driven nanorobots (MNRs) for use as maneuverable immunoassay probes that facilitate a strategy for an automated and highly efficient ELISA analysis, termed nanorobots enabled ELISA (nR-ELISA). To prepare the MNRs, the self-assembled chains of FeO magnetic particles are chemically coated with a thin layer of rigid silica oxide (SiO), onto which capture antibody (Ab1) is grafted to further achieve magnetically maneuverable immunoassay probes (MNR-Ab1s). We investigate the fluid velocity distribution around the MNRs at microscale using numerical simulation and empirically identify the mixing efficiency of the actively rotating MNRs. To automate the analysis process, we design and fabricate by 3-D printing a detection unit consisting of three function wells. The MNR-Ab1s can be steered into different function wells for required reaction or wishing process. The actively rotating MNR-Ab1s can enhance the binding efficacy with target analytes at microscale and greatly decrease incubation time. The integrated nR-ELISA system can significantly reduce the assay time, more importantly during which process manpower input is greatly minimized. Our simulation of the magnetic field distribution generated by Helmholtz coils demonstrates that our approach can be scaled up, which proves the feasibility of using current strategy to construct high throughput nR-ELISA detection instrument. This work of taking magnetic micro/nanobots as active immunoassay probes for automatic and efficient ELISA not only holds great potential for point-of-care testing (POCT) in future but also extends the practical applications of self-propelled micro/nanorobots into the field of analytical chemistry.
作为分析化学中一种典型的、经典的、但功能强大的生化传感技术，酶联免疫吸附测定（ELISA）在定量分析超低浓度分析物方面表现出卓越的性能和广泛的实用性。然而，较长的孵育时间和繁琐的多步洗涤过程使得传统 ELISA 效率低下且劳动强度大。在这里，我们提出了棒状磁驱动纳米机器人（MNRs）作为可操纵的免疫分析探针，用于实现自动化和高效的 ELISA 分析策略，称为纳米机器人增强的 ELISA（nR-ELISA）。为了制备 MNRs，FeO 磁性颗粒的自组装链通过化学方法涂覆一层薄的刚性氧化硅（SiO），在其上接枝捕获抗体（Ab1），以进一步实现可磁操纵的免疫分析探针（MNR-Ab1s）。我们使用数值模拟研究了 MNR 周围的微尺度流体速度分布，并通过经验确定了主动旋转 MNR 的混合效率。为了自动化分析过程，我们通过 3D 打印设计和制造了一个由三个功能井组成的检测单元。MNR-Ab1s 可以被引导到不同的功能井中进行所需的反应或处理过程。主动旋转的 MNR-Ab1s 可以增强与微尺度目标分析物的结合效力，并大大缩短孵育时间。集成的 nR-ELISA 系统可以显著缩短检测时间，更重要的是，在此过程中大大减少了人力投入。我们对亥姆霍兹线圈产生的磁场分布的模拟表明，我们的方法可以扩展，这证明了使用当前策略构建高通量 nR-ELISA 检测仪器的可行性。这项将磁性微/纳米机器人作为主动免疫分析探针用于自动和高效 ELISA 的工作不仅在未来具有即时检测（POCT）的巨大潜力，而且还将自推进微/纳米机器人的实际应用扩展到分析化学领域。
