RAPID: COVID: Optofluidic sensor array for rapid and sensitive detection of COVID-19 antibodies

COVID-19已造成数万人死亡，并正在成为对全球健康的严重威胁。检测COVID-19感染、追踪治疗效果和验证疫苗接种成功的方法之一是测量人体内产生的抗体。不幸的是，目前的抗体检测要么依赖于昂贵的集中实验室的复杂仪器，而且需要很长时间才能得到结果，要么依赖于基于纸的试纸，虽然快速（5-20分钟），但只能产生是/否的结果，这使得这种方法很容易产生假阳性/阴性，并且无法跟踪患者对感染、治疗和疫苗接种的反应。因此，迫切需要一种能够快速、灵敏、准确测量多种COVID-19相关抗体的便携式设备来诊断早期感染并监测患者的反应。该项目的设备基于便携式微流体系统，可在护理点快速、准确、灵敏地测量血液中的抗体，从而可以检测COVID-19感染并跟踪人体抗体的发展。本项目旨在将微流控激光技术与微流控ELISA（酶联免疫吸附试验）技术相结合，开发快速、高灵敏度的传感器阵列，用于指尖血液中COVID-19相关IgG和IgM的多路检测。主要有三个方面的工作：(1)研制用于全血血清提取的微流控芯片；(2)将激光传感技术与传统的荧光酶联免疫吸附试验（ELISA）相结合，实现抗体（IgG、IgM）的灵敏检测，动态范围大；(3)用人工加样进行检测。该设备具有以下优点：(1)周转时间快。它具有高度便携性，可用于现场快速筛查患者，而无需将样本送到集中实验室。(2)高度定量。这对于显著减少假阳性/阴性和监测患者的感染轨迹以及对治疗和疫苗接种的反应至关重要。(3)灵敏度高，动态范围大。结合激光技术，我们期望将抗体检测限提高10倍，动态范围提高10倍。更高的灵敏度可以更早地诊断感染，防止疾病从无症状患者广泛传播。大的动态范围可以方便地跟踪患者抗体随时间的演变。(4)通用性强。该装置可用于快速检测新冠肺炎患者死亡原因之一的细胞因子释放综合征（CRS）。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

COVID-19 has caused tens of thousands of deaths and is becoming a severe threat to global health. One of the methods to detect COVID-19 infection, track the treatment effectiveness, and validate successful vaccination, is to measure the antibodies developed in human bodies. Unfortunately, current antibody detection relies on either complicated instruments in a centralized lab which is expensive and takes a long time to get the results, or a paper-based test strip, which, while quick (5-20 minutes), produces only Yes/No results, making this method very easy to generate false positives/negative and impossible to track the patients’ response to infection, treatment, and vaccination. Therefore, a portable device that can rapidly, sensitively, and accurately measure multiple COVID-19 related antibodies is urgently needed to diagnose early infection and monitoring patients’ response. The device in the project is based on a portable microfluidic system to rapidly, accurately, and sensitively measure the antibodies in blood at point-of-care, which allows for the detection of COVID-19 infection and tracking of antibody development in human bodies.The objective of the project is to combine microfluidic laser technology and microfluidic ELISA (enzyme-linked immunosorbent assay) technology to develop rapid and highly sensitive sensor array for multiplexed detection of COVID-19 related IgG and IgM using fingertip blood. There are three tasks: (1) to develop a microfluidic chip to extract serum from whole blood; (2) to integrate the laser sensing technology with traditional fluorescence ELISA to sensitively detect antibodies (IgG and IgM) with a large dynamic range; (3) to test with artificially spiked samples. The device provides the following advantages. (1) Quick turn-around time. It is highly portable and can be used to rapidly screen patients on-site, rather than sending samples to centralized labs. (2) Highly quantitative. This is critical to significantly reducing the false positives/negatives and monitoring the patients’ infection trajectories and response to treatment and vaccination. (3) Highly sensitive and large dynamic range. Combined with the lasing technology, we expect to improve the antibody detection limit 10X with 10X larger dynamic range. Higher sensitivity enables earlier diagnosis of infection, preventing wide disease spread from those asymptomatic patients. A large dynamic range enables to easily track patients’ antibody evolution over time. (4) Highly versatile. The device can be adapted to rapidly detect cytokine release syndrome (CRS), which is one of the death causes in COVID-19 patients.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.