Point of care microfluidic diagnosis system for rapid and sensitive detection of

用于快速、灵敏检测的护理点微流体诊断系统

• 批准号: 8695281
• 负责人: Michel G. Bergeron
• 金额: $ 77.93万
• 依托单位: LAVAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695281
• 关键词: Adenoviruses; American; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antiviral Agents; Antiviral resistance; Avian Influenza; Award; Bedside Testings; Bioinformatics; Biological Assay; Birds; California; Canada; Categories; Chemistry; Clinical; Clinical Virology; Communicable Diseases; Communication; DNA; DNA amplification; Data; Databases; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Ensure; Fluorescence; Genes; Genomics; Goals; Health; Health Information System; Health Technology; Healthcare Systems; Hospitals; Hour; Human; Industry; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Institutes; Label; Lasers; Measures; Mechanics; Medical; Methods; Microfabrication; Microfluidic Microchips; Microfluidics; Molecular; National Institute of Allergy and Infectious Disease; National Research Council; Nucleic Acids; One-Step dentin bonding system; Optics; Parainfluenza; Patients; Pharmacologic Substance; Plastics; Polymerase Chain Reaction; Polymers; Preclinical Testing; Preparation; Prize; Procedures; Process; Product Approvals; Public Health; Quarantine; RNA; RNA amplification; Reaction; Reading; Reagent; Research; Research Personnel; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Reverse Transcriptase Polymerase Chain Reaction; SARS coronavirus; Sampling; Science; Scientist; Societies; Specialist; Specimen; Surface; Swab; System; Technology; Technology Transfer; Test Result; Time; United States National Institutes of Health; Universities; Validation; Viral; Viral Antigens; Viral Respiratory Tract Infection; Virus; Work; authority; base; biodefense; contagion; cost; cost effective; density; design; flu; improved; instrument; instrumentation; internal control; meetings; micro-total analysis system; microbial; nanofabrication; novel diagnostics; pandemic disease; pathogen; point of care; point-of-care diagnostics; pre-clinical; prevent; product development; research clinical testing; respiratory virus; response; sample collection; swine flu; tool; viral RNA; virology

DESCRIPTION (provided by applicant): The objective of this proposal is to merge genomics, microfluidics, DNA and RNA amplification, microarrays, analytical instrumentation development and polymer microfabrication expertises to develop a revolutionary medical diagnostic device for the rapid multiparametric detection of the most relevant viruses found in respiratory tract clinical samples. Viral respiratory tract infection (VRTI) is the most common illness today (Fendrick et al., 2003), and costs over $50 billion yearly in the US alone. It is estimated that more than a dozen different viruses infect human upper airways, yet current diagnostic methods based on viral antigens often lack the required sensitivity, while culture-based methods are extremely slow. Universit¿ Laval with its collaborators intends to integrate their already existing diagnostic technologies into a single Microfluidic Centripetal Device (MCD), or Lab-on-a-Chip, for the detection of VRTIs (VRTI-MCD). The VRTI-MCD will automatically (i) process nasopharyngeal swab samples, (ii) extract viral RNA/DNA in a sufficiently pure form, (iii) amplify and label nucleic acids, (iv) process labelled-amplicons, (v) hybridize amplicons on low density microarrays, (vi) read and interpret the data to provide a clinically useful result within one hour, and (vii) communicate results in real-time to health information systems. The VRTI-MCD will be a disposable polymer-based device that will encase all necessary reagents. The disposable will be processed by a portable and easy-to-use opto-mechanical instrument enabling automated VRTI diagnostics. Seventeen viruses, including influenza A (such as avian flu and swine flu), influenza B, SARS coronavirus, parainfluenza, and adenovirus responsible for the majority of VRTI along with key antiviral resistance markers will be detectable using a single VRTI-MCD. This novel diagnostic platform will be developed and optimized using nasopharyngeal swab specimens available in the extensive clinical samples collection at the Centre de Recherch¿ en Infectiologie (CRI). By the end of year-five support by NIH, we will have validated the integrated VRTI-MCD using human clinical samples and the portable instrument will be ready for worldwide clinical testing for diagnostics at the point-of-care. Thereafter, within two years, product development and approval by health authorities (FDA, Health Canada, etc.) will be undertaken by a commercial partner. This new technological platform will result in an unprecedented expansion of point-of-care diagnostic tests (POCTs) for viral respiratory tract infections, while providing rapid yet economical molecular diagnostics results in less than one hour instead of the current 2-3 days. This will improve medical response, allowing for the timely use of proper antiviral drugs and to ensure that rapid quarantine measures only be used when appropriate. These POCTs will help public health authorities to define new operational strategies for both lab-based and field-based applications.

描述（应用程序提供）：该提案的目的是合并基因组学，微流体，DNA和RNA扩增，微阵列，分析仪器开发和聚合物微型制造专业知识，以开发革命性的医学诊断设备，以在呼吸道临床样品中发现的最相关的多余病毒的革命性医学诊断设备。病毒呼吸道感染（VRTI）是当今最常见的疾病（Fendrick等，2003），仅在美国，每年的费用超过500亿美元。据估计，有十几个不同的病毒感染了人类上呼吸道，但是基于病毒抗原的当前诊断方法通常缺乏所需的敏感性，而基于培养的方法的较慢。 Laval及其合作者打算将其现有的诊断技术集成到单个微流体中心设备（MCD）或CHIP实验室中，以检测VRTIS（VRTI-MCD）。 VRTI-MCD将自动（i）处理鼻咽拭子样品，（ii）以充分纯净的形式提取病毒RNA/DNA，（III）放大和标记核酸，（iv）过程标记为标记 - （iv）在一个小时中添加了临床，并解释了临床上的临床，并解释了（VI），并解释了数据，并解释了数据，并解释了数据，并解释了数据，并在数据中读取了a nimplicons（v）。 （vii）实时传达结果与健康信息系统。 VRTI-MCD将是一种基于一次性聚合物的设备，它将包含所有必要的试剂。一次性且易于使用的光学机械仪器将处理一次自动化VRTI诊断的仪器。包括影响力大多数VRTI的腺病毒，包括影响力的17个病毒，包括影响力（例如禽流感和猪流感），影响力B，SARS冠状病毒，parainfluenza和腺病毒，以及关键的抗病毒药耐药标记物，使用单个VRTI-MCD可检测到。这个新颖的诊断平台将使用鼻咽拭子标本进行开发和优化，该标本可在Infectiologie（CRI）中心的广泛临床样本集合中提供。到NIH的五年级支持之前，我们将使用人类临床样本验证了综合的VRTI-MCD，并且便携式仪器将准备好在全球范围内进行诊断。此后，在两年之内，卫生当局（FDA，加拿大卫生部等）将由商业合作伙伴进行产品开发和批准。这个新的技术平台将导致病毒呼吸道感染的护理点诊断测试（POCTS）的前所未有的扩展，同时提供了不到一小时而不是当前的2-3天，提供了快速而经济的分子诊断。这将改善医疗反应，允许及时使用适当的抗病毒药物，并确保仅在适当时才使用快速隔离措施。这些POCT将帮助公共卫生当局为基于实验室和基于现场的应用程序定义新的操作策略。

项目成果

Latex micro-balloon pumping in centrifugal microfluidic platforms.

• DOI: 10.1039/c3lc51116b
• 发表时间: 2014-03-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Aeinehvand MM;Ibrahim F;Harun SW;Al-Faqheri W;Thio TH;Kazemzadeh A;Madou M
• 通讯作者: Madou M

Structured oligonucleotides for target indexing to allow single-vessel PCR amplification and solid support microarray hybridization.

用于靶标索引的结构化寡核苷酸，可实现单容器 PCR 扩增和固相支持微阵列杂交。

• DOI: 10.1039/c4an01352b
• 发表时间: 2015
• 期刊: The Analyst
• 作者: Girard,LaurieD;Boissinot,Karel;Peytavi,Régis;Boissinot,Maurice;Bergeron,MichelG
• 通讯作者: Bergeron,MichelG

The effect of contact angles and capillary dimensions on the burst frequency of super hydrophilic and hydrophilic centrifugal microfluidic platforms, a CFD study.

• DOI: 10.1371/journal.pone.0073002
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kazemzadeh A;Ganesan P;Ibrahim F;He S;Madou MJ
• 通讯作者: Madou MJ

Theoretical development and critical analysis of burst frequency equations for passive valves on centrifugal microfluidic platforms.

• DOI: 10.1007/s11517-012-1020-7
• 发表时间: 2013-05
• 期刊: Medical & biological engineering & computing
• 影响因子: 3.2
• 作者: Thio TH;Soroori S;Ibrahim F;Al-Faqheri W;Soin N;Kulinsky L;Madou M
• 通讯作者: Madou M

Development of a passive liquid valve (PLV) utilizing a pressure equilibrium phenomenon on the centrifugal microfluidic platform.

• DOI: 10.3390/s150304658
• 发表时间: 2015-02-25
• 期刊: Sensors (Basel, Switzerland)
• 作者: Al-Faqheri W;Ibrahim F;Thio TH;Bahari N;Arof H;Rothan HA;Yusof R;Madou M
• 通讯作者: Madou M