A scalable aptamer-based electrochemical biosensor for rapid detection of SARS-CoV-2 from saliva

一种基于适配体的可扩展电化学生物传感器，用于快速检测唾液中的 SARS-CoV-2

• 批准号: 10320990
• 负责人: Jeffrey Ly
• 金额: $ 49.04万
• 依托单位: MPOD, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-21 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320990
• 关键词: 2019-nCoV; Affinity; Antibodies; Binding; Biosensor; Businesses; CLIA certified; COVID-19; COVID-19 detection; COVID-19 intervention; COVID-19 pandemic; COVID-19 point of care; COVID-19 test; COVID-19 testing; Cells; Cellular Phone; Communication; Communities; Contracts; Country; Custom; Data; Data Collection; Databases; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Disease Outbreaks; Electrodes; Electronics; Ensure; Enzyme-Linked Immunosorbent Assay; Family; Future; Goals; Gold; Health Personnel; Health Professional; Healthcare Systems; Immobilization; Individual; Institution; Manufacturer Name; Methods; Noise; Nucleic Acids; Oligonucleotides; Patients; Performance; Periodicity; Phase; Population; Process; Production; Proteins; Public Health; Reagent; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Saliva; Sampling; Schools; Security; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Swab; System; Tablets; Technology; Test Result; Testing; Time; Viral Proteins; Virus; antigen diagnostic; aptamer; base; cloud storage; cost; data infrastructure; density; design; detector; digital; education resources; encryption; follow-up; high risk; improved; miniaturize; mobile application; novel; novel diagnostics; pandemic disease; pathogen; point of care; point-of-care detection; public health emergency; rapid detection; rapid diagnosis; rapid technique; response; saliva sample; test strip; wireless

Abstract The COVID-19 pandemic is a critical global public health emergency and many countries are failing to contain the virus's spread due to slow and insufficient testing. While several diagnostic methods are now available, most tests are either reagent-intensive and must be done in CLIA-approved labs, making them expensive and slow to report results, or rapid and inexpensive, but potentially lacking in sensitivity. In the U.S., seriously ill and high- risk patients have been prioritized for testing, causing states to miss mild and asymptomatic cases, some of which are the most effective spreaders of the virus. However, expanding testing has been a challenge due to shortages of sampling swabs and key reagents for nucleic acid amplification-based tests, which are the most popular option. Testing capabilities must be expanded exponentially to enable mass population-level testing of all patients, healthcare workers and their families, other critical key workers, and the wider community in order to bring the pandemic under control. mPOD proposes to expand testing capabilities through a novel biosensor that will use oligonucleotide molecules called aptamers to bind to unique sites on the SARS-CoV-2 virus. Aptamers have similar binding affinities to antibodies, but due to their smaller size, they are more agile, making them particularly suited for high-specificity binding. To complete the test, a saliva sample will be loaded onto a test strip containing aptamers immobilized onto gold electrodes. The gold-electrode test strip will be inserted into the mPOD DTCT, a proprietary electrochemical test platform where virus-bound aptamers will be detected via cyclic voltammetry, triggering a positive result. The result is sent wirelessly via a mobile app, which sends encrypted data on to the cloud for storage and to public health agencies for enhanced data collection, tracking, and tracing of COVID-19. The app will also include a backend database to help businesses, manufacturers, schools, and large institutions track tested individuals' results and tailor specific public health responses. In order to further develop this technology and enable rapid deployment for timely COVID-19 intervention, mPOD plans to 1) Select SARS-CoV-2-specific aptamers for use in electrode test strips with an optimized signal-to-noise ratio performance, 2) Demonstrate sensitivity and specificity of a low-cost, miniaturized potentiostat test strip for use as a COVID-19 POC or OTC diagnostic, 3) Complete and test a fully-fledged digital infrastructure for data collection, tracking, and tracing of COVID-19 test results via the mPOD mobile app. This non-traditional approach will provide new testing capabilities with the potential to report results faster than standard RT-PCR tests and with greater accuracy and sensitivity compared to existing antigen-based diagnostics. Furthermore, once the system is developed, test strips with customized aptamers can be developed for rapid diagnosis of other pathogens, including future emerging pandemics, via routine POC and OTC testing.

抽象的 COVID-19 大流行是全球严重的公共卫生紧急事件，许多国家未能遏制 由于检测缓慢且不充分，病毒得以传播。虽然现在有多种诊断方法可用，但大多数 测试要么是试剂密集型的，必须在 CLIA 批准的实验室中进行，这使得它们昂贵且缓慢 报告结果，或者快速且廉价，但可能缺乏敏感性。在美国，重病和高危人群 高风险患者被优先接受检测，导致各州错过了轻症和无症状病例，其中一些 它们是病毒最有效的传播者。然而，扩大测试一直​​是一个挑战，因为 核酸扩增检测的采样拭子和关键试剂短缺，这是最严重的问题 受欢迎的选择。测试能力必须呈指数级扩展，以实现大规模人群水平的测试 所有患者、医护人员及其家人、其他关键工作人员以及更广泛的社区 使疫情得到控制。 mPOD 提议通过新型生物传感器扩展测试能力 它将使用称为适体的寡核苷酸分子与 SARS-CoV-2 病毒上的独特位点结合。 适体与抗体具有相似的结合亲和力，但由于尺寸较小，因此更加灵活，使得 它们特别适合高特异性结合。为了完成测试，唾液样本将被加载到 含有固定在金电极上的适体的测试条。将金电极测试条插入 mPOD DTCT，一个专有的电化学测试平台，通过该平台可以检测病毒结合的适体 循环伏安法，触发阳性结果。结果通过移动应用程序无线发送，该应用程序发送 加密数据传输到云端进行存储，并传输到公共卫生机构以增强数据收集、跟踪、 以及 COVID-19 的追踪。该应用程序还将包括一个后端数据库，以帮助企业、制造商、 学校和大型机构跟踪测试者的结果并制定具体的公共卫生应对措施。为了 为了进一步开发这项技术并实现快速部署以及时进行 COVID-19 干预，mPOD 计划 1) 选择 SARS-CoV-2 特异性适体用于具有优化信噪比的电极测试条 性能，2) 展示低成本、小型恒电位仪测试条的灵敏度和特异性 作为 COVID-19 POC 或 OTC 诊断，3) 完成并测试成熟的数据数字基础设施 通过 mPOD 移动应用程序收集、跟踪和追溯 COVID-19 检测结果。这种非传统的方法 将提供新的测试功能，有可能比标准 RT-PCR 测试更快地报告结果， 与现有的基于抗原的诊断相比，具有更高的准确性和灵敏度。此外，一旦 系统开发完毕，可开发带有定制适配体的试纸，用于其他疾病的快速诊断 通过常规 POC 和 OTC 检测来检测病原体，包括未来出现的流行病。