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

RAPID：COVID：光流控传感器阵列，用于快速、灵敏地检测 COVID-19 抗体

• 批准号: 2029484
• 负责人: Xudong Fan
• 金额: $ 14.92万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029484&HistoricalAwards=false
• 关键词: RAPID; COVID; Optofluidic; sensor; array

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.

COVID-19已造成数万人死亡，并正成为全球健康的严重威胁。检测COVID-19感染、跟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，当前的抗体检测要么依赖于集中实验室中的复杂仪器，价格昂贵，需要很长时间才能获得结果，要么依赖于纸质测试条，虽然速度快（5-20分钟），但只产生是/否结果，使得这种方法非常容易产生假阳性/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，以诊断早期感染和监测患者的反应。该项目中的设备基于便携式微流体系统，可以快速，准确，灵敏地测量血液中的抗体，该项目的目标是将联合收割机微流控激光技术和微流控ELISA相结合，（酶联免疫吸附测定）技术，以开发快速和高灵敏度的传感器阵列，用于使用指尖血液多重检测COVID-19相关IgG和IgM。有三项任务：（1）开发微流控芯片，从全血中提取血清;（2）将激光传感技术与传统荧光ELISA相结合，灵敏检测动态范围大的抗体（IgG和IgM）;（3）用人工加标样品进行检测。该装置具有以下优点。(1)快速周转时间。它具有高度便携性，可用于现场快速筛查患者，而不是将样本发送到集中实验室。(2)高度量化。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)高灵敏度和大动态范围。结合激光技术，我们预计将抗体检测限提高10倍，动态范围扩大10倍。更高的灵敏度可以更早地诊断感染，防止无症状患者的广泛疾病传播。大的动态范围使得能够容易地跟踪患者抗体随时间的演变。(4)多才多艺。该设备可用于快速检测细胞因子释放综合征（CRS），这是COVID-19患者的死亡原因之一。该奖项反映了NSF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。

项目成果

Rapid and quantitative detection of SARS-CoV-2 specific IgG for convalescent serum evaluation

• DOI: 10.1016/j.bios.2020.112572
• 发表时间: 2020-12-01
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Tan, Xiaotian;Krel, Mila;Fan, Xudong
• 通讯作者: Fan, Xudong