MMDx: A rapid multiplexed matrix code diagnostic for real time epidemiology

MMDx：用于实时流行病学的快速多路复用矩阵代码诊断

• 批准号: 8467676
• 负责人: Lee Gehrke
• 金额: $ 19.56万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467676
• 关键词: Ambulatory Health Center; Antibodies; Antigens; Area; Attention; Biological; Biology; Blood; Car Phone; Chemicals; Code; Colombia; Communicable Diseases; Coupling; Critical Care; Data; Dengue; Dengue Virus; Detection; Development; Device Designs; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Ebola virus; Engineering; Epidemiology; Equipment; Evaluation; Goals; Gold; Hospitals; Human Resources; Immune response; Immunoglobulin G; Immunoglobulin M; Incidence; Individual; Infection; Infectious Agent; Knowledge; Laboratories; Lateral; Logistics; Medical; Methods; Military Personnel; Monoclonal Antibodies; Movement; PTPN11 gene; Pathogen detection; Patients; Persons; Phase; Physical Chemistry; Positioning Attribute; Preparation; Process; Prospective Studies; Proteins; Public Health; Readiness; Reagent; Risk; Sampling; Scientist; Sensitivity and Specificity; Serotyping; Serum; Site; Specificity; Technology; Testing; Time; Validation; Viral Proteins; Virus Diseases; Work; base; biodefense; cost; design; design and construction; disease diagnosis; multiplex detection; nanoparticle; nanorod; novel diagnostics; pathogen; point of care; point-of-care diagnostics; prototype; public health relevance; response; two-dimensional; viral detection; virus identification

DESCRIPTION (provided by applicant): This proposal describes the design, construction, and testing of a rapid multiplexed matrix code diagnostic for select biodefense and emerging pathogens. The threat of biological attacks underscores a critical need for rapid point-of care diagnostics that identify specific pathogens in infected persons. Infected or at-risk individuals may be far from critical-care facilities; therefore, diagnostic tests must be easily transportable, stable in storage, simple to use, and easy to interpret. Lateral flow tests (also called immunochromatographic tests or strip tests) are a well-established diagnostic platform because of their simplicity, rapid readout, and low cost qualitative/semi-quantitative detection of antibodies or antigens. Nonetheless, the lack of available point-of-care diagnostics for infectious diseases represents vulnerability in biodefense preparedness as well as a gap in serving public health needs. We propose novel diagnostic device designs, including quick response (QR) two-dimensional matrix-coded readouts, along with attention to chemical coupling approaches, to increase the sensitivity and broaden the multiplex capabilities of lateral flow devices. Effective public health responses also require knowledge of disease distribution and movement based on diagnostic data. Therefore, our proposed Multiplexed Matrix Diagnostic (MMDx) device will be machine-readable, representing a field diagnostic with integrated capability for real time epidemiology using mobile phone technologies and geographic positioning. We have assembled an interdisciplinary team of scientists, engineers, and medical doctors who understand the biology of, and immune responses to infectious agents, the physical chemistry of detection methods, the fabrication methods required to produce diagnostic devices, the technology for providing real-time responsive epidemiology, and the processes required for validating a diagnostic device under field conditions. Our goals for the exploratory/pilot (R21) phase are to develop a prototype two-dimensional matrix barcode-based, machine-readable diagnostic to detect pathogens in blood or serum. The prototype will offer 1) direct identification of the four different dengue virus serotypes by detecting circulating viral protein NS1, as well as 2) indirect Ebola virus and dengue virus identification by detecting circulating antibodies against the viral proteins. A field-based feasibility test archival patient serum samples collected from dengue virus-infected individuals will provide initial validation of the specificity and sensitivit of the prototype and enable power calculations to determine numbers of required patients prior to the R33 developmental phase. For the Developmental Phase (R33), our goals will be to extend the MMDx device multiplex capabilities for detecting additional biodefense agent infections in a point-of-care analysis. The full potential of the MMDx diagnostic and real-time epidemiology will be evaluated in a one-month hospital-based field test in Bucaramanga, Colombia, which has a high incidence of dengue virus infections.

描述（由申请人提供）：本提案描述了用于选择生物防御和新兴病原体的快速多重矩阵代码诊断的设计、构建和测试。生物攻击的威胁突出表明，迫切需要快速的护理点诊断，以确定感染者体内的特定病原体。受感染或处于危险中的个体可能远离重症监护设施;因此，诊断测试必须易于运输， 储存稳定，使用简单，易于解释。侧流试验（也称为免疫层析试验或试纸条试验）是一个完善的诊断平台，因为它们简单，快速读出，和低成本的抗体或抗原的定性/半定量检测。尽管如此，缺乏可用的感染性疾病的即时诊断， 疾病是生物防御准备工作的薄弱环节，也是满足公共卫生需要的一个缺口。我们提出了新的诊断设备的设计，包括快速响应（QR）二维矩阵编码读出，沿着注意化学偶联方法，以增加灵敏度和拓宽的多路复用能力的侧流设备。有效的公共卫生对策还需要根据诊断数据了解疾病分布和移动情况。因此，我们提出的多重矩阵诊断（MMDx）设备将是机器可读的，代表了一个现场诊断与集成能力的真实的时间流行病学使用移动的电话技术和地理定位。我们已经组建了一个由科学家，工程师和医生组成的跨学科团队，他们了解传染性病原体的生物学和免疫反应，检测方法的物理化学，生产诊断设备所需的制造方法，提供实时响应流行病学的技术，以及在现场条件下验证诊断设备所需的过程。我们的探索/试点（R21）阶段的目标是开发一种基于二维矩阵条形码的机器可读诊断原型，以检测血液或血清中的病原体。原型将提供1）直接识别 四种不同的登革热病毒血清型通过检测循环病毒蛋白NS 1，以及 2)通过检测循环抗体间接鉴定埃博拉病毒和登革热病毒 病毒蛋白从登革病毒感染个体中收集的存档患者血清样本将提供原型特异性和灵敏度的初步验证，并进行功效计算，以确定R33开发阶段之前所需的患者数量。对于开发阶段（R33），我们的目标是扩展MMDx设备的多重功能，以便在床旁分析中检测其他生物防御剂感染。MMDx诊断和实时流行病学的全部潜力将在哥伦比亚布卡拉曼加的一个为期一个月的医院现场测试中进行评估，该地区登革热病毒感染率很高。