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

用于即时诊断的混合集成分子分析 (HIMAS)

基本信息

批准号：
8468115
负责人：
Holger Schmidt
金额：
$ 19.06万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8468115
关键词：
Anthrax disease Antigens Area Biological Biomedical Research Categories Clinical Communicable Diseases Complex Decision Making Detection Devices Diagnosis Diagnostic Differential Diagnosis Disease Management Disease Outbreaks Early Diagnosis Environment Epidemic Fluorescence Foundations Genetic Genetic screening method Glass Goals Health Human Hybrids Junin virus Measures Medicine Microfluidics Mission Molecular Molecular Analysis Monitor National Institute of Allergy and Infectious Disease Nucleic Acids Optics Outcome Patient Isolation Patients Phase Point-of-Care Systems Polymerase Chain Reaction Population Preparation Principal Investigator Process Public Health Research Research Activity Research Institute Resources Respiratory Tract Infections Sampling Silicon Solutions Speed Structure System Technology Testing Texas United States National Institutes of Health Validation Viral Viral Hemorrhagic Fevers Viral Load result Virus Whole Blood Work base biodefense clinically relevant combinatorial digital effective therapy hemorrhagic fever virus high risk infectious disease treatment innovation instrument mortality multiplex detection novel strategies nucleic acid detection pathogen point of care point-of-care diagnostics programs prototype response screening viral detection weapons

项目摘要

DESCRIPTION (provided by applicant): Highly infectious diseases originating from bacterial (e.g., anthrax) or viral (e.g. Ebola) pathogens with high mortality rates pose high risks, includin 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 o biodefense pathogens and other viral and bacterial threats to human health.

描述（由申请人提供）：源自细菌的高度传染性疾病（例如，高死亡率的病原体（如炭疽）或病毒（如埃博拉）构成高风险，包括流行病爆发和使用这些病原体作为生物武器的敌对行为。在“护理点”检测和快速反应的能力对于应对这些威胁至关重要。尽管研究活动有所增加，但由于当前检测方法的缺点，包括缺乏速度（培养），缺乏准确性（抗原测试）和缺乏简单性（聚合酶链反应（PCR），在很大程度上是由于需要扩增遗传靶物质），目前还没有建立针对这些病原体的即时护理系统。我们的长期目标是开发使用光流体的即时医疗设备-在单个芯片规模系统上集成光学和微流体的组合。本申请的目的是证明和验证适用于A类病原体鉴别床旁诊断的混合集成分子分析系统（HIMAS）。我们的中心假设是，这可以通过结合两种强大的微流体和光学技术来实现，这些技术针对单独芯片层中的样品处理和无扩增检测进行了优化。在R21阶段，我们的目标将通过以下具体目标来实现：（1）引入一种新的光谱目标复用方法，使用干涉波导结构;（2）引入一种新的混合光流体系统，由玻璃微流体层和硅光学层组成;（3）建立一个平台，用于使用临床样品鉴别诊断出血热病毒。在随后的R33阶段，我们将在这些创新的基础上开发一种便携式原型系统，该系统可以快速区分14种可武器化的出血热病毒，而无需从全血患者样本开始进行靶扩增。所提出的方法的创新贡献是：（i）使用多模干涉仪（MMI）波导进行光谱、空间和组合目标复用的干涉激发;（ii）引入新的平面光流体系统，具有单独优化的层，用于样品处理和无扩增核酸分析。拟议的工作是重要的，因为它克服了关键的障碍，以开发一个点的护理系统的PCR免费，差异诊断生物防御病原体和其他病毒和细菌对人类健康的威胁。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microfluidic System for Detection of Viral RNA in Blood Using a Barcode Fluorescence Reporter and a Photocleavable Capture Probe.

DOI：
10.1021/acs.analchem.7b03527
发表时间：
2017-11-21
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Du K;Park M;Griffiths A;Carrion R;Patterson J;Schmidt H;Mathies R
通讯作者：
Mathies R

Multiplexed efficient on-chip sample preparation and sensitive amplification-free detection of Ebola virus.

DOI：
10.1016/j.bios.2016.12.071
发表时间：
2017-05-15
期刊：
Biosensors & bioelectronics
影响因子：
12.6
作者：
Du K;Cai H;Park M;Wall TA;Stott MA;Alfson KJ;Griffiths A;Carrion R;Patterson JL;Hawkins AR;Schmidt H;Mathies RA
通讯作者：
Mathies RA

Optofluidic analysis system for amplification-free, direct detection of Ebola infection.

DOI：
10.1038/srep14494
发表时间：
2015-09-25
期刊：
Scientific reports
影响因子：
4.6
作者：
Cai H;Parks JW;Wall TA;Stott MA;Stambaugh A;Alfson K;Griffiths A;Mathies RA;Carrion R;Patterson JL;Hawkins AR;Schmidt H
通讯作者：
Schmidt H

Hybrid optofluidic integration.