Development or improvement of clinical diagnostic tests for SARS-CoV-2 to increase the sensitivity, specificity and ability to provide rapid results

开发或改进 SARS-CoV-2 的临床诊断测试,以提高敏感性、特异性和提供快速结果的能力

基本信息

  • 批准号:
    10171494
  • 负责人:
  • 金额:
    $ 50.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-11 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

Abstract Unmet Need: q-rtPCR technology has dominated COVID-19 diagnostics and public health screening. Independent of the test developer, q-rtPCR has been shown to have an unusually high false negative rate: 15% up to 48% (1). According to the Covid Tracking Project. as of May 16th, 2020, 11 Million COVID-19 tests had been administered in the US (2). With 15% false negative rate, approximately 1.65M people would be falsely classified as free of infection. As might be expected, meta-analysis has shown that the false negative rate for q-rtPCR “explodes” before day 7 of infection (3) when viral load is still low, to render q-rtPCR ineffective as a tool for detecting weakly symptomatic carriers early, while also lessening its value in epidemiology (4). The Solution: PathogenDx has invented, patented and developed a microarray-based test, DetectX-Rv, and has submitted it for FDA-EUA review to screen for COVID-19 in NP swabs. The microarray has the capacity to test for multiple viral analytes in parallel with [SARS-CoV-2] as the primary analyte under FDA submission. Content Enhancement. We propose here the addition of a newly identified COVID-19 clade variant, which has been hypothesized by others to be more infective (5). DetectX-Rv already contains content needed to test SARS-CoV-2 plus multiple other coronavirus [SARS-CoV, MERS-CoV, CoV 229E,CoV OC43, CoV NL63, CoV HKU1] plus influenza + [PanA & Pan B] which are defined as a set as a “Pan-Respiratory” Virus Test. However for the development proposed in this RO1, this “extra” coronavirus content will be rationally modified and used instead as a large set of specificity controls. Other sources of funding outside this RO1 will be used to develop the full Pan-Respiratory virus content, as a separate product. Based on the work completed thus far, including April 15, 2020 filing to the FDA, we propose that with RO1 funding, the new test variant (DetectX-Rv-v2) can be made ready (by Q2) for deployment with NP swab collection as an automated 96 array/SBS plate COVID-19 test (@576 tests/shift). Sensitivity Improvement. The DetectX-Rv test is based on two Tandem Endpoint PCR reactions in series [Enrichment + Labeling] coupled to microarray hybridization. This technical approach gives rise to detection at single nucleotide resolution over a 6-log sample input dynamic range. Most importantly, the [Tandem PCR + Hybridization] assay routinely generates a Lowest Limit of Detection (LLOD) <1 genome per reaction. We anticipate that with this approach, we will routinely detect COVID-19 (signal/noise >20x background) at only 1 viral genome per reaction. Preliminary data, including that submitted to the FDA EUA program, suggests that the LLOD for DetectX-Rv will be roughly 10x lower than for an optimized q-RT-PCR reaction. Thus, with the DetectX-Rv test, COVID-19 should be routinely detected at 100 virus particles/swab. Specificity Enhancement. DetectX-Rv (144 tests) has enormous test capacity relative to q-rtPCR, which has allowed DetectX-Rv to monitor 3 different sites in the SARS-CoV-2 genome and a human RNA control, concurrently (N1,N2,N3,P) along with a panel of 8 viral controls all performed in parallel and in triplicate, thus allowing confirmation of COVID-19 signals with experimental specificity >10x than attainable with q-rtPCR. In the proposed RO1 program, that redundant COVID-19 content will be amended (DetectX-Rv-v2) to include a recently-identified clade variant S-D614G (5) so that initial and variant clades can be measured concurrently. Throughput Enhancement. We are near completion of a program to deploy full automation of DetectX-Rv function. As a short term RO1 deliverable, we will develop, by Sept 1, 2020, an integrated suite of technology for processing 576 NP swab or saliva tests/shift, in a 96 microarray/SBS plate format, based on the labor burden of 1 technician. The 96 well format employs the same printing technology already in use and the same (patented) microarray fabrication chemistry and is thus low risk. However, by completing the transition to the 96 well format, we will have achieved 12,000 arrays/day manufacturing scale, which with support from equity other sources, could be immediately scaled to 48,000 per day. Based the requirements of PAR-20-178, we propose 4 Specific Aims to support this 2 year RO1 program. SA1. Q1. Add Clade & Coronavirus Content Enabling Analysis of SARS-CoV-2 & variants. SA2. Q2. Sensitivity/specificity analysis of DetectX-Rv-v2 vs qRT-PCR predicate: Clinical Specimens SA3. Q3-5. Simplify DetectX-Rv-v2 Throughput via One pot RT-PCR & Hybridization Rate Enhancement. SA4. Q5-8. Enhance & Validate DetectX-Rv Performance to Diagnose Asymptomatic Transmission
摘要 未得到满足的需求:Q-RT-PCR技术主导了新冠肺炎的诊断和公共健康筛查。 与测试显影剂无关,Q-RTPCR已被证明具有异常高的假阴性率: 15%至48%(1)。根据Covid跟踪项目。截至2020年5月16日,有1100万次新冠肺炎测试 曾在美国接受过治疗(2)。以15%的假阴性率,大约165万人 被错误地归类为无感染的。不出所料,荟萃分析显示,假阴性 在病毒载量仍然很低的情况下,Q-RTPCR在感染第7天前“爆炸”的比率(3),从而产生Q-RTPCR 作为早期发现症状较弱的携带者的工具无效,同时也降低了其在 流行病学(4)。 解决方案:PathgenDx已经发明、申请了专利并开发了一种基于微阵列的测试DetectX-RV,以及 已将其提交美国食品和药物管理局欧洲药品监督管理局审查,以筛选NP拭子中的新冠肺炎。该微阵列具有以下能力 在FDA提交的文件中,同时测试多种病毒分析物和作为主要分析物的[SARS-CoV-2]。 内容增强。我们建议在这里添加一个新发现的新冠肺炎分支变体,它 被其他人假设为更具感染力(5)。DetectX-RV已包含测试所需的内容 SARS-CoV-2加上多种其他冠状病毒[SARS-CoV、MERS-CoV、CoV 229E、CoV OC43、CoV NL63、CoV [HKU1]加上流感病毒[PANA&PANB],被定义为一套“泛呼吸道”病毒测试。 然而,对于这一RO1中提出的开发,这种额外的冠状病毒内容将是合理的 修改后作为一大套特异性对照使用。此RO1以外的其他资金来源 将用于开发完整的泛呼吸道病毒内容,作为单独的产品。基于这项工作 到目前为止,包括2020年4月15日提交给FDA的文件,我们建议用RO1资金,新的测试 变种(DetectX-RV-v2)可以准备好(到第二季度),以便作为自动化的NP拭子收集进行部署 96阵列/SBS板新冠肺炎测试(@576测试/班次)。 敏感度提高。DetectX-RV检测是基于两个串联的终点聚合酶链式反应 [浓缩+标记]与微阵列杂交相结合。这种技术方法会在 单核苷酸分辨率在6个对数样本输入动态范围内。最重要的是,[串联PCR+ 杂交]检测通常产生最低检测下限(Llod)和每个反应1个基因组。 我们预计,使用这种方法,我们将在以下位置常规检测新冠肺炎(信号/噪声&gt;20x背景) 每个反应只有一个病毒基因组。初步数据,包括提交给FDA EUA计划的数据表明 DetectX-RV的检测灵敏度大约比优化的Q-RT-PCR反应低10倍。因此,有了 检测X-RV试验,新冠肺炎应常规检出100个病毒颗粒/拭子。 特异性增强。与Q-RTPCR相比,DetectX-RV(144个测试)具有巨大的测试能力,后者具有 允许DetectX-RV监测SARS-CoV-2基因组中的3个不同位置和人类RNA对照, 同时(N1,N2,N3,P)和8个病毒对照小组一起,全部并行和三重执行,因此 允许确认新冠肺炎信号,其实验特异性是Q-RTPCR的10倍。在……里面 拟议的RO1计划,冗余的新冠肺炎内容将被修改(DetectX-RV-v2),以包括 最近发现的分支变异S-D614G(5),以便可以同时测量初始和变异分支。 吞吐量增强。我们即将完成部署DetectX-RV全自动化的计划 功能。作为一项短期RO1交付成果,我们将在2020年9月1日之前开发一套集成的技术 用于处理576个NP拭子或唾液测试/移位,以96微阵列/SBS平板格式,基于劳动力 1名技术员的负担。96孔格式使用已在使用的相同打印技术和相同的 (专利)微阵列制造化学,因此风险低。但是,通过完成向 96井格式,我们将实现12,000个阵列/天的制造规模,这在股权的支持下 其他来源,可能立即扩大到每天48,000人。 根据PAR-20-178的要求,我们提出了4个具体目标来支持这个为期2年的RO1计划。 SA1.问题1.添加分支和冠状病毒内容,支持分析SARS-CoV-2及其变种。 SA2.Q2.DetectX-RV-v2与qRT-PCR检测的敏感性/特异性分析:临床标本 SA3.Q3-5。通过一锅RT-PCR和杂交率增强简化检测X-RV-v2吞吐量。 SA4.Q5-8。增强和验证DetectX-RV性能以诊断无症状传播

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MICHAEL E. HOGAN其他文献

MICHAEL E. HOGAN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MICHAEL E. HOGAN', 18)}}的其他基金

Development or improvement of clinical diagnostic tests for SARS-CoV-2 to increase the sensitivity, specificity and ability to provide rapid results
开发或改进 SARS-CoV-2 的临床诊断测试,以提高敏感性、特异性和提供快速结果的能力
  • 批准号:
    10237413
  • 财政年份:
    2020
  • 资助金额:
    $ 50.21万
  • 项目类别:
A New Filter Paper Technology for Flavivirus Collection, Shipping, and Analysis
用于黄病毒收集、运输和分析的新型滤纸技术
  • 批准号:
    9348101
  • 财政年份:
    2017
  • 资助金额:
    $ 50.21万
  • 项目类别:
High-Throughput HLA-Typing: on Raw, Unpurified Cord Blood Samples
高通量 HLA 分型:针对原始、未纯化的脐带血样本
  • 批准号:
    8262309
  • 财政年份:
    2012
  • 资助金额:
    $ 50.21万
  • 项目类别:
High-Throughput HLA-Typing: on Raw, Unpurified Cord Blood Samples
高通量 HLA 分型:针对原始、未纯化的脐带血样本
  • 批准号:
    8457136
  • 财政年份:
    2012
  • 资助金额:
    $ 50.21万
  • 项目类别:
The Transfusion Chip: A Simple, Low Cost Microarray for DNA Based Blood Typing
输血芯片:一种简单、低成本的微阵列,用于基于 DNA 的血型分析
  • 批准号:
    8199053
  • 财政年份:
    2011
  • 资助金额:
    $ 50.21万
  • 项目类别:
The Transfusion Chip: Phase II Technology Validation
输血芯片:二期技术验证
  • 批准号:
    8454205
  • 财政年份:
    2011
  • 资助金额:
    $ 50.21万
  • 项目类别:
A Low Cost Microarray for Population-Scale AIDS Risk Analysis: The AIDS Chip
用于人口规模艾滋病风险分析的低成本微阵列:艾滋病芯片
  • 批准号:
    7755340
  • 财政年份:
    2009
  • 资助金额:
    $ 50.21万
  • 项目类别:
RISK/TOX CHIP PROGRAM
风险/毒物芯片计划
  • 批准号:
    2864884
  • 财政年份:
    1998
  • 资助金额:
    $ 50.21万
  • 项目类别:
MULTI PARAMETER ANALYSIS OF MRNA LEVELS IN LUNG TISSUE
肺组织 mRNA 水平的多参数分析
  • 批准号:
    6494928
  • 财政年份:
    1998
  • 资助金额:
    $ 50.21万
  • 项目类别:
RISK/TOX CHIP PROGRAM
风险/毒物芯片计划
  • 批准号:
    6178636
  • 财政年份:
    1998
  • 资助金额:
    $ 50.21万
  • 项目类别:

相似海外基金

Treecle - data and automation to unlock woodland creation in the UK to achieve net zero
Treecle - 数据和自动化解锁英国林地创造以实现净零排放
  • 批准号:
    10111492
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    SME Support
STTR Phase II: Optimized manufacturing and machine learning based automation of Endothelium-on-a-chip microfluidic devices for drug screening applications.
STTR 第二阶段:用于药物筛选应用的片上内皮微流体装置的优化制造和基于机器学习的自动化。
  • 批准号:
    2332121
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Cooperative Agreement
Improving access to AI automation to support new digital offerings within Professional/Financial Services
改善对人工智能自动化的访问,以支持专业/金融服务中的新数字产品
  • 批准号:
    10095096
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Collaborative R&D
Cost-Effective, AI-driven Automation Technology for Cell Culture Monitoring: Boosting Efficiency and Sustainability in Industrial Biomanufacturing and Streamlining Supply Chains
用于细胞培养监测的经济高效、人工智能驱动的自动化技术:提高工业生物制造的效率和可持续性并简化供应链
  • 批准号:
    10104748
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Launchpad
Sustainable Remanufacturing solution with increased automation and recycled content in laser and plasma based process (RESTORE)
可持续再制造解决方案,在基于激光和等离子的工艺中提高自动化程度和回收内容(RESTORE)
  • 批准号:
    10112149
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    EU-Funded
Next-generation automation and PAT implementation for QbD and enhanced approaches for cell and gene therapy
QbD 的下一代自动化和 PAT 实施以及细胞和基因治疗的增强方法
  • 批准号:
    10087446
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Collaborative R&D
SBIR Phase II: Radar-based Building Automation
SBIR 第二阶段:基于雷达的楼宇自动化
  • 批准号:
    2335079
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Cooperative Agreement
Automation and cost reduction of the hardware and software components of a novel indoor sustainable vertical growing solution
新型室内可持续垂直种植解决方案的硬件和软件组件的自动化和成本降低
  • 批准号:
    83007861
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Innovation Loans
Artificial intelligence coupled to automation for accelerated medicine design
人工智能与自动化相结合,加速药物设计
  • 批准号:
    EP/Z533038/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Research Grant
CAREER: Algorithm-Hardware Co-design of Efficient Large Graph Machine Learning for Electronic Design Automation
职业:用于电子设计自动化的高效大图机器学习的算法-硬件协同设计
  • 批准号:
    2340273
  • 财政年份:
    2024
  • 资助金额:
    $ 50.21万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了