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

新冠肺炎已造成数万人死亡，并正在成为全球健康的严重威胁。检测新冠肺炎感染、追踪治疗效果、验证疫苗接种成功的方法之一是检测人体内产生的抗体。不幸的是，目前的抗体检测要么依赖于中央实验室中复杂的仪器，昂贵且需要很长时间才能得到结果，要么依赖于纸质试纸，虽然快速(5-20分钟)，但只能产生是/否结果，使得这种方法很容易产生假阳性/阴性，并且不可能跟踪患者对感染、治疗和疫苗的反应。因此，迫切需要一种能够快速、灵敏、准确地检测多种新冠肺炎相关抗体的便携式设备，以诊断早期感染并监测患者的反应。该项目基于便携式微流控系统，能够快速、准确、灵敏地检测护理现场血液中的抗体，从而实现对新冠肺炎感染的检测和对人体抗体发展的跟踪。本项目的目标是将微流控激光技术和微流控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，利用指端血进行新冠肺炎相关免疫球蛋白和免疫球蛋白M的多重检测。(1)研制从全血中提取血清的微流控芯片；(2)将激光传感技术与传统的荧光酶联免疫吸附试验相结合，灵敏地检测大动态范围的抗体(Ig G和Ig M)；(3)用人工添加的样品进行检测。该装置具有以下优点。(1)快速周转时间。它具有很高的便携性，可以用于现场快速筛查患者，而不是将样本发送到中央实验室。(2)量化程度高。这对于显著减少假阳性/阴性以及监测患者的感染轨迹和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，我们期望将抗体的检测下限提高10倍，动态范围扩大10倍。更高的敏感性可以更早地诊断感染，防止疾病从那些没有症状的患者广泛传播。大的动态范围使其能够轻松跟踪患者抗体随时间的演变。(4)通用性强。该设备可用于快速检测细胞因子释放综合征(CRS)，这是新冠肺炎患者的死因之一。该奖项反映了美国国家科学基金会的法定使命，通过使用基金会的智力优势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.