An urgently needed low-cost, rapidly deployable platform for simultaneous SARS-CoV-2 viral particle and COVID-19 IgG/IgM detection and quantification

通过采用Nodexus开发的低成本技术，在当前 NCI第一阶段SBIR奖，我们在此建议一个低成本、可快速部署的平台，用于量化 同时从唾液中提取SARS-CoV-2病毒颗粒和抗SARS-CoV-2抗体 基于珠粒的捕获在简单的流通式分析中进行，利用专利进行低基础设施筛查 微流控节点-孔道检测(NPS)，以紧急满足负担得起的诊断和 无症状携带者检测保护高危人群，包括癌症患者和 免疫功能受损的幸存者。建议的解决方案进一步支持快速部署以进行测试 中心，并最终实现患者/个人的无障碍使用，具有通用的基于Web的兼容性 (包括移动设备)，以最大限度地方便公众使用和采用。 非常需要像Nodexus平台这样的家庭诊断解决方案，因为世界 目前正处于由严重急性呼吸综合征冠状病毒2引起的全球大流行中，或 2019年底，从武汉出现的SARS-CoV-2病毒，中国。截至2020年5月23日，目前有 全世界报告了500万例以上的病例，不幸的是超过338,000人死亡(平均死亡率~7%，数据来自 ECDC每日跟踪)。目前缺乏直接的病毒颗粒诊断测试，这给我们带来了巨大的 世界各国政府有负担限制经济和社会活动，以防止社区进一步 新冠肺炎的传播。最近的研究表明，在新冠肺炎发生严重事件的风险是 在癌症患者中，这一比例在统计学上显著更高。这可能会给他们的客户带来巨大的障碍 支持系统(例如家人和朋友的探访)，并且在就诊时也会导致恐惧和安全问题 用于体检、监测和治疗。Nodexus建议的平台(系统和基于盒式磁带的套件)解决方案 将提供一种负担得起的、可在家中部署的诊断测试，可以直接检测到两种病毒 使用唾液样本快速(20分钟后)检测新冠肺炎抗体和抗体 诊断/监测患者，特别侧重于帮助不同受影响的人群，包括 癌症患者和免疫功能受损的幸存者。 出于多种原因，唾液被选为最佳诊断样本类型。首先，唾液样本有 与FDA/CDC标准诊断试验相比，检测SARS-CoV-2的符合率为93% 鼻咽吸出液(NPA)。其次，唾液是患者最容易自我采集的样本，没有 鼻咽/口咽拭子不适或可能出血，且无痰难 自己收钱。最后，患者自己收集唾液已被证明显著降低了病毒传播到 与更具侵入性的方法相比，这可能会导致 咳出痰或窒息。Nodexus提出的平台最终将检测病毒颗粒和IgM/IgG 抗体具有较高的敏感性、特异性和与NPA qRT-PCR检测的一致性。 成功完成拟议的目标将大大有助于诊断冠状病毒感染 最早阶段(在需要住院之前)。Nodexus处于有利地位，能够完成这些目标 在基于先前证明的低成本高利润率的墨盒生产的紧急时间表内 使用标准和专有的内部流程，重要的面向制造的设计已经 已执行，并且因为大多数提议的平台组件已经 作为NCI第一阶段SBIR的一部分，由现有外部合作伙伴开发/集成到Nodexus的现有产品中 获奖。

By adapting low-cost technology developed by Nodexus prior to and during the course of the current NCI Phase I SBIR award, we hereby propose a low-cost, rapidly deployable platform for quantification of both SARS-CoV-2 viral particles and anti-SARS-CoV-2 IgG/IgM antibodies simultaneously from saliva by bead-based capture in a simple flow-through assay for low-infrastructure screening utilizing patented microfluidic Node-Pore Sensing (NPS) to urgently address the need for affordable diagnostics and asymptomatic carrier detection to protect at-risk populations including cancer patients and immunocompromised survivors. The proposed solution further enables rapid deployment to testing centers and ultimately patient/individual walk-up usability with universal web-based compatibility (including mobile device) for maximum accessibility and adoption for the general public. There is great need for an at-home diagnostic solution like the proposed Nodexus platform because the world is currently in the midst of a global pandemic caused by severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, which emerged from Wuhan, China at the end of 2019. As of May 23, 2020, there are currently over >5M cases reported worldwide, and tragically over 338,000 deaths (average mortality rate ~7%, data from ECDC daily tracker). The lack of direct viral particle diagnostic tests currently available has placed an immense burden on governments around the world to curtail economic and social activities to prevent further community spread of COVID-19. Recent studies have shown that risk of developing severe events in COVID-19 is statistically significantly higher in cancer patients. This can present enormous hurdles for engaging with their support system (e.g. family and friend visits) and also lead to fear and safety issues when attending clinical sites for checkups, monitoring, and treatment. Nodexus’ proposed platform (system and cartridge-based kit) solution would offer an affordable, at-home-deployable diagnostic test that would directly detect both the virus and antibodies against COVID-19 in a rapid manner (<20 minutes to result) using saliva samples to diagnose/monitor patients, with particular focus to assist disparately affected populations including cancer patients and immunocompromised survivors. Saliva was chosen as the optimal diagnostic sample type for a number of reasons. Firstly, saliva samples have a >93% concordance of detection for SARS-CoV-2 as compared to FDA/CDC standard diagnostic test using nasopharyngeal aspirate (NPA). Secondly, saliva is the easiest sample for patients to self-collect, without the discomfort or potential bleeding of nasopharyngeal/oropharyngeal swabs, and without the difficulty of sputum to self-collect. Finally, patient self-collecting of saliva significantly has been shown to lower risk of virus spread to healthcare workers or nearby members of the public compared to more invasive methods which may result in expectoration or sternutation. Nodexus’ proposed platform will ultimately detect viral particles and IgM/IgG antibodies with high sensitivity, specificity, and concordance with NPA qRT-PCR assays. Successful completion of the proposed Aims will significantly contribute to diagnosing COVID infection at the earliest stages (prior to hospitalization becoming needed). Nodexus is well positioned to complete the Aims within the urgent timeline based on the previously demonstrated low-cost cartridge production with high margins using standard as well as proprietary in-house processes, significant design-for-manufacturing already being performed, and because the majority of the proposed platform components have already been developed/integrated into Nodexus’ existing products by existing external partners as part of NCI Phase I SBIR award.