Hybrid integrated molecular analysis (HIMAS) for point-of-care diagnostics

主要研究者/项目负责人：施密特，霍尔格 项目摘要 由细菌（如炭疽）或病毒（如埃博拉）引起的高度传染性疾病 高死亡率的病原体构成高风险，包括流行病爆发和敌对 将这些病原体用作生物武器。快速检测和反应的能力， “护理点”对于应对这些威胁至关重要。尽管研究活动有所增加， 目前还没有建立针对这些病原体的即时护理系统 目前的检测方法的缺点，包括缺乏速度（文化），缺乏 准确性（抗原测试），缺乏简单性（聚合酶链反应（PCR），在很大程度上 由于需要扩增遗传靶物质）。我们的长期目标是发展点- 使用光流控技术护理生物医学设备-集成光学和 微流控技术在一个芯片规模的系统上。本申请的目的是证明 并验证适用于以下方面的混合集成分子分析系统（HIMAS）： A类病原体的护理点鉴别诊断。我们的核心假设是， 可以通过结合两种强大的微流体和光学技术来实现， 优化的样品处理和在单独的芯片层中的无扩增检测。 在R21的初始阶段，我们将通过以下具体目标实现目标： (1)介绍了一种新的基于干涉波导的光谱目标复用方法 （2）介绍了一种新的混合光流控系统， 和硅光学层;（3）将平台用于出血性疾病的鉴别诊断 使用临床样本的发热病毒。在随后的R33阶段，我们将在这些基础上进行构建 通过开发一种便携式原型系统，可以快速区分14种 可武器化的出血热病毒，而不需要目标扩增，从 病人的全血样本拟议办法的创新贡献是： 使用多模干涉仪（MMI）波导进行干涉激发， 空间和组合靶向多路复用;（ii）引入新的平面光流体系统 具有针对样品处理和无扩增核酸单独优化的层 分析.拟议的工作是重要的，因为它克服了关键的障碍， 开发一种无需PCR的即时护理系统，用于生物防御的鉴别诊断 病原体和其他病毒和细菌对人类健康的威胁。 1

Principal Investigator/Program Director: Schmidt, Holger Project Summary Highly infectious diseases originating from bacterial (e,g, anthrax) or viral (e.g. Ebola) pathogens with high mortality rates pose high risks, including epidemic outbreaks and hostile acts using these pathogens as biological weapons. The ability to detect and respond rapidly at the "point of care" is essential for dealing with these threats. Despite increased research activity, there is currently no established point-of-care system for these pathogens due to the shortcomings of the current detection approaches, including lack of speed (culture), lack of accuracy (antigen tests), and lack of simplicity (polymerase chain reaction (PCR), in large part due to the need to amplify the genetic target material). Our long-term goal is to develop point-of- care biomedical devices using optofluidics - the combination of integrated optics and microfluidics on a single chip-scale system. The objective of this application is to demonstrate and validate a Hybrid, Integrated Molecular Analysis System (HIMAS) that is suitable for differential point-of-care diagnosis of category A pathogens. Our central hypothesis is that this can be accomplished by combining two powerful microfluidic and optical technologies that are optimized for sample processing and amplification-free detection in separate chip layers. During the initial R21 phase, our objectives will be accomplished by the following specific aims: (1) Introduce a new spectral target multiplexing approach using interferometric waveguide structures; (2) Introduce a new hybrid optofluidic system composed of a glass microfluidic layer and a silicon optical layer; (3) Validate the platform for differential diagnostics of hemorrhagic fever viruses using clinical samples. In a subsequent R33 phase, we will build on these innovations by developing a portable prototype system that can rapidly distinguish between 14 weaponizable hemorrhagic fever viruses without the need for target amplification, starting from a whole blood patient sample. The innovative contributions of the proposed approach are: (i) interferometric excitation using multi-mode interferometer (MMI) waveguides for spectral, spatial, and combinatorial target multiplexing; (ii) introduction of a new planar optofluidic system with layers optimized individually for sample processing and amplification-free nucleic acid analysis. The proposed work is significant because it overcomes the critical barriers to developing a point-of-care system for PCR-free, differential diagnostics of biodefense pathogens and other viral and bacterial threats to human health. 1