Benchmarking the Sensitivity and Specificity of the Herringbone Microfluidic Device for Rare Particle Capture

对稀有粒子捕获人字​​形微流体装置的灵敏度和特异性进行基准测试

• 批准号: 10891904
• 负责人: Brian Vala Nahed
• 金额: $ 2.69万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10891904
• 关键词: 2019-nCoV; Acceleration; Administrative Supplement; Attention; Bar Codes; Benchmarking; Biological Assay; Biology; Blinded; Blood; Blood Tests; Brain Neoplasms; Cancer Patient; Clinic; Communities; Complex; Data; Data Analyses; Data Coordinating Center; Databases; Deposition; Development; Device or Instrument Development; Devices; Diagnostic Equipment; Diagnostic Procedure; Ensure; Focus Groups; Future; Glioblastoma; Information Management; Infrastructure; Laboratories; Metadata; Microfluidic Microchips; Neoplasm Circulating Cells; Parents; Patients; Performance; Procedures; Process; Production; Publications; Quality Control; RADx Radical; RNA; Reproducibility; Research Personnel; Running; Sampling; Sensitivity and Specificity; Specificity; System; Technology; Testing; Time; Transcript; Translations; United States National Institutes of Health; Validation; Viral; Viremia; Virus; Water; Work; comparative; cost; data harmonization; data hub; data sharing; data standards; database of Genotypes and Phenotypes; detection limit; diagnostic panel; diagnostic technologies; digital; extracellular vesicles; liquid biopsy; method development; nanoparticle; nanoscale; new technology; pandemic disease; particle; programs; quality assurance; rapid testing; research and development; technology validation; tool

PROJECT SUMMARY Many new technologies are developed and validated on the bench of the investigator, but few have the opportunity to test their performance with blinded, control samples. The lack of standards can be due to the novelty of technology or processing conditions, or simply the uncertainly of the underlying biology within patients. This is particularly challenging for liquid biopsy assays, as universal standards are desperately lacking, further slowing down future translation to the clinic. Through our work with the RADx-Rad program, we have begun validation testing for the parent technology featured in our R01 application: the ‘herringbone chip’, or EVHB-Chip. The use of their blinded samples has been powerful, both validating our internal findings, while also catching the attention of the regulatory agencies and other researchers. For this proposed study, we will conduct our most complex validation panel yet, a full challenge panel to evaluate specificity and sensitivity of our assay, testing over 100 blinded samples. This work will be done quickly, as we have all the tools and staff in place to test these samples in one month’s time. We will have full data harmonization with the NIH DCC, to ensure consistency, data standardization, and data deposits to the dbGAP database. Each sample is uniquely barcoded and the contents will include a set concentration of nanoscale analytes for us to test with the concentration varying from 1x to 4x our limit of detection. Contaminating analytes are also added to these samples, to allow for specificity to be determined. We will run each sample through our device, extract the RNA using our automated system, quantify the amount of and types of RNA transcripts detected and share the data with the DCC. This will trigger an automatic data unblinding, data transformation and analysis, allowing us to quickly assess device performance. In addition to getting this critical device validation work completed, the resulting publication will establish a new standard for diagnostic device development, which includes multi-party R&D efforts.

项目摘要 许多新技术在调查员的台上得到了开发和验证，但是很少有人拥有 通过盲目的控制样品测试其性能的机会。缺乏标准可能是由于 技术或加工条件的新颖性，或者仅仅是患者内部生物学的不确定的。 对于液体活检分析，这尤其具有挑战性，因为普遍的标准迫切缺乏，进一步 放慢未来的翻译到诊所。通过与RADX-RAD计划的合作，我们已经开始 我们的R01应用程序中介绍的父技术的验证测试：“人字芯片”或EVHB-Chip。 他们盲人样本的使用非常有力，既证实了我们的内部发现，同时也抓住了 监管机构和其他研究人员的关注。对于这项拟议的研究，我们将进行最多的 复杂的验证面板，这是一个完整的挑战小组，以评估我们评估的特异性和灵敏度，测试 超过100个盲人样本。这项工作将很快完成，因为我们拥有所有工具和人员来测试这些 一个月的样本。我们将与NIH DCC建立完整的数据协调，以确保一致性， 数据标准化以及数据存储到DBGAP数据库。每个样品都是独特的条形码，并且 内容将包括纳米级分析物的设定浓度，以使我们测试的浓度因 1倍至4倍我们的检测极限。污染分析物也添加到这些样品中，以允许特异性 要确定。我们将通过设备运行每个样品，使用自动化系统提取RNA， 量化检测到的RNA转录本的数量和类型，并与DCC共享数据。这将触发 自动数据不闪烁，数据转换和分析，使我们能够快速评估设备 表现。除了完成此关键设备验证工作之外，由此产生的出版物还将 为诊断设备开发建立新的标准，其中包括多方研发工作。