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

描述（由申请人提供）：本提案描述了针对特定生物防御和新兴病原体的快速复用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，迫切需要在护理点进行快速诊断，以确定感染者体内的特定病原体。受感染或有风险的个人可能远离重症监护机构；因此，诊断测试必须易于运输，

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.