A handheld plug-and-play microfluidic liquid handling automation platform for immunoassays

Lab-on-a-chip technologies and microfluidics have pushed miniaturized liquid handling to unprecedented precision, integration, and automation, which improved the reaction efficiency of immunoassays. However, most microfluidic immunoassay systems still require bulky infrastructures, such as external pressure sources, pneumatic systems, and complex manual tubing and interface connections. Such requirements prevent plug-and-play operation at the point-of-care (POC) settings. Here we present a fully automated handheld general microfluidic liquid handling automation platform with a plug-and-play ‘clamshell-style’ cartridge socket, a miniature electro-pneumatic controller, and injection-moldable plastic cartridges. The system achieved multi-reagent switching, metering, and timing control on the valveless cartridge using electro-pneumatic pressure control. As a demonstration, a SARS-CoV-2 spike antibody sandwich fluorescent immunoassay (FIA) liquid handling was performed on an acrylic cartridge without human intervention after sample introduction. A fluorescence microscope was used to analyze the result. The assay showed a limit of detection comparable to some previously reported enzyme-linked immunosorbent assays (ELISA). In addition to automated liquid handling on the cartridge, the system can operate as a 6-port pressure source for external microfluidic chips. A rechargeable battery with a 12V 3000mAh capacity can power the system for 42 hours. The footprint of the system is 16.5×10.5×7 cm, and the weight is 801g, including the battery. The system can find many other POC and research applications requiring complex liquid manipulation, such as molecular diagnostics, cell analysis, and on-demand biomanufacturing.

芯片实验室（Lab-on-a-chip）技术与微流控技术已将微型化液体处理的精度、集成度与自动化水平提升至前所未有的高度，进而提高了免疫测定的反应效率。然而，绝大多数微流控免疫测定系统仍依赖庞大的外围设备，例如外部压力源、气动系统，以及复杂的人工管路与接口连接。此类限制使其无法在床旁检测（Point-of-Care, POC）场景下实现即插即用操作。本研究提出一款全自动化手持通用型微流控液体处理平台，配备即插即用的“翻盖式”微流控卡盒插槽、微型电动气动控制器，以及可注塑成型的塑料微流控卡盒。该平台通过电动气动压力控制，实现了无阀微流控卡盒上的多试剂切换、定量与时序控制。作为演示验证，研究人员在丙烯酸材质的微流控卡盒上开展了新型冠状病毒（SARS-CoV-2）刺突抗体夹心荧光免疫测定（Fluorescent Immunoassay, FIA），样本加入后无需人工干预即可完成全流程液体处理。采用荧光显微镜对检测结果进行分析。该检测方法的检出限可与此前部分已报道的酶联免疫吸附测定（Enzyme-Linked Immunosorbent Assay, ELISA）相媲美。除可实现微流控卡盒上的自动化液体处理外，该平台还可作为6端口压力源，为外部微流控芯片提供支持。该平台配备12V 3000mAh容量的可充电电池，可支持系统连续运行42小时。该系统的整机外形尺寸为16.5×10.5×7 cm，整机重量（含电池）为801克。该平台还可应用于诸多其他需要复杂液体操控的床旁检测与科研场景，例如分子诊断、细胞分析以及按需生物制造等。