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在当前项目之前和期间开发的低成本技术， NCI第一阶段SBIR奖，我们在此提出了一个低成本，快速部署的平台，量化 SARS-CoV-2病毒颗粒和抗SARS-CoV-2 IgG/IgM抗体， 基于微珠的捕获，在简单的流通分析中进行低基础设施筛选， 微流控节点孔传感（Node-Pore Sensing），以紧急解决对负担得起的诊断的需求， 无症状携带者检测，以保护包括癌症患者在内的高危人群， 免疫功能低下的幸存者所提出的解决方案进一步支持快速部署到测试 中心和最终患者/个人无障碍可用性，具有通用的基于Web的兼容性 （包括移动终端），以最大限度地方便公众使用。 非常需要像Nodexus平台这样的家庭诊断解决方案，因为世界 目前正处于严重急性呼吸系统综合征冠状病毒2型引起的全球大流行之中，或 SARS-CoV-2于2019年底在中国武汉出现。截至2020年5月23日， 全球报告的病例超过500万例，不幸的是，死亡人数超过338，000例（平均死亡率约为7%，数据来自 ECDC每日追踪器）。目前缺乏直接的病毒颗粒诊断测试， 世界各国政府的负担，以减少经济和社会活动，以防止进一步的社区 COVID-19的传播。最近的研究表明，在COVID-19中发生严重事件的风险 在癌症患者中有统计学意义的高。这可能会给他们的参与带来巨大的障碍。 支持系统（例如家人和朋友访问），并且在参加临床研究中心时也会导致恐惧和安全问题 进行检查、监测和治疗。Nodexus提出的平台（系统和基于插件的套件）解决方案 将提供一个负担得起的，在家里部署的诊断测试，将直接检测病毒， 和抗COVID-19抗体的快速方式（<20分钟的结果）使用唾液样本， 诊断/监测患者，特别侧重于帮助受影响的人群，包括 癌症患者和免疫功能低下的幸存者。 选择唾液作为最佳诊断样本类型有多种原因。首先，唾液样本有 与FDA/CDC标准诊断测试相比，SARS-CoV-2检测的一致性>93%， 鼻咽抽吸物（NPA）。其次，唾液是患者最容易自行采集的样本， 鼻咽/口咽拭子的不适或潜在出血，并且没有痰液的困难， 最后，患者自行收集唾液已被证明可以显著降低病毒传播的风险， 与更具侵入性的方法相比，医护人员或附近的公众可能会导致 咳痰或打喷嚏。Nodexus提出的平台最终将检测病毒颗粒和IgM/IgG 抗体具有高灵敏度、特异性和与NPA qRT-PCR测定的一致性。 成功完成拟议的目标将大大有助于诊断COVID感染， 早期阶段（需要住院治疗之前）。Nodexus有能力完成目标 在紧急的时间轴内，基于先前展示的具有高利润的低成本墨盒生产 使用标准以及专有的内部流程，重要的制造设计已经在 由于大多数拟议的平台组成部分已经完成， 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 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.