A multimodal platform for Oral screening of COVID-19

原文摘要 新冠肺炎口腔筛查的多模式平台 从现成的口腔标本中开发快速可靠的传感器系统对于筛查和 SARS-CoV-2感染的管理。除了需要实验室规模的仪器的测试外，开发 快速检测可以在疫情管理中发挥及时作用。目前的快速检测通常涉及到一种 横向流动格式检测病毒蛋白质组分，根据实施情况，可能会导致相对较高的 错误程度。InnoTech与麻省理工学院合作，提议开发基于以下技术的多路传输传感器平台 能够进行分子结合和后续报告的纳米材料。我们将开发并商业化一种多路传输 使用纳米材料报告器的传感器平台，可快速同时检测病毒的多种成分 颗粒在电场中适用的电化学装置。对于我们的第一阶段-目标1，我们将专注于开发和 用于准确检测SARS-CoV-2病毒蛋白质和核酸的合成生物传感器的优化。我们的里程碑 是否发现和验证了一系列针对蛋白质和核酸片段的分子识别生物传感器 SARS-CoV-2。我们将在4个月内完成这一阶段。在第二阶段-目标1中，我们将制定和验证 电化学探测器。我们将利用在目标1中识别和验证的合成生物传感器来进行电化学 使用感染的多个生物标志物快速检测活跃的SARS-CoV-2感染的平台。我们会 专门使用商用的一次性电极平台和现有的Metrohm恒电位器 DropSens可简化扩展和商业化。我们的里程碑，将在第二阶段的第一年完成，将拥有一个 多路生物传感器芯片和带有多路生物传感器芯片和恒电位器的阿尔法原型，我们将 对照现有新冠肺炎诊断，作为灵敏度和定量准确性的基准。在第二阶段-目标2中，我们将 用回溯性临床标本验证原型芯片和检测器，为EUA-FDA提交做准备。 我们将确定LOD、临床表现以及与其他呼吸道病原体和正常菌群的交叉反应。 这一目标的里程碑是记录至少两种蛋白质和两种核酸生物传感器的复合-- CoV-2将在口腔样本中提供每微升5-20个病毒的LOD，并将通过临床验证 30例阳性标本和30例阴性标本与RT-PCR的符合率均在95%以上。

Original Abstract A multimodal platform for Oral screening of COVID-19 The development of a rapid and reliable sensor system from readily available oral specimens is crucial for the screening and management of SARS-CoV-2 infection. Other than tests that require laboratory-scale instrumentation, the development of rapid tests can play a timely role in the management of an outbreak. Current rapid tests often involve the antibodies in a lateral flow format to detect viral protein components and, depending on the implementation, can result in a relatively high degree of error. In partnership with MIT, InnoTech proposes the development of a multiplexed sensor platform based on nanomaterials capable of molecular binding and subsequent reporting. We will develop and commercialize a multiplexed sensor platform using nanomaterial reporters capable of rapid simultaneous detection of multiple components of viral particles in a field applicable electrochemical device. For our Phase I- Aim 1 we will focus on the development and optimization of synthetic biosensors for accurate detection of SARS-CoV-2 viral proteins and nucleic acid. Our milestone is the discovery and validation an array of molecular recognition biosensors against both protein and nucleic acid segments of SARS-CoV-2. We will complete this phase in 4 months. In Phase II-Aim 1, we will develop and validate the electrochemical detectors. We will utilize the synthetic biosensors identified and validated in Aim 1 to an electrochemical platform for the rapid detection of an active SARS-CoV-2 infection using multiple biomarkers of the infection. We will specifically employ commercially-available, disposable electrode platforms and existing potentiostats from Metrohm DropSens to streamline scale-up and commercialization. Our milestone, to be completed in year 1 of Phase II, is to have a multiplex biosensor chip and an alpha prototype with a multiplex biosensor chip and a potentiostat reader which we will benchmark for sensitivity and quantitative accuracy against existing COVID-19 diagnostics. In Phase II-Aim 2, we will validate the prototype chips and detectors with retrospective clinical specimens in preparation for EUA-FDA submission. We will determine the LOD, clinical performance, and cross-reactivity with other respiratory pathogens and normal flora. The milestone for this Aim is to document a multiplex of at least two proteins and two nucleic acid biosensors for SARS- CoV-2 that will provide a LOD of 5-20 viruses per microliter in an oral specimen and will be clinically validated with greater than 95% concordance with RT-PCR in 30 positive and 30 negative specimens.