权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Nonspecific DNA Sensors for Scalable Pathogen Diagnostics

用于可扩展病原体诊断的非特异性 DNA 传感器

基本信息

批准号：
2017712
负责人：
Rebekah Drezek
金额：
$ 26万
依托单位：
William Marsh Rice University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2017712&HistoricalAwards=false
关键词：
Nonspecific DNA Sensors Scalable Pathogen

项目摘要

The rapid identification of pathogens is essential for clinical diagnostics and biodefense. Given timely information, clinicians can prescribe better treatments and slow the rise of drug resistant bacteria, and U.S. biosurveillance efforts can track the emergence and spread of both existing and newly evolved pathogens. While most rapid diagnostic tests have sensors that are each specialized to detect only one kind of pathogen, this research effort is developing new DNA sensing techniques to efficiently detect large numbers of pathogens with just a few sensors. By minimizing the number of necessary sensors, new pathogen surveillance devices could be portable and inexpensive for routine use. The technology additionally provides an approach to detecting emerging novel pathogens without the need to create and deploy new test kits. In addition to furthering development of new pathogen identification technologies, the project develops a hands-on experimental module exploring this methodology and implements it in a biosensing and imaging course serving undergraduate and graduate engineering students at Rice University. This research effort applies compressed sensing which allows just a few DNA probes to (1) give each species a fingerprint response and (2) unmix these fingerprint signals when a few pathogens are in the same sample. Compressed sensing assumes that the sample is sparse. Sparsity occurs because although there may be dozens or hundreds of possible species to account for, any single sample from a patient or the environment will have only a few pathogens of interest for relevant applications. For pathogen detection, DNA probes each bind multiple times to microbial species. The number of binding events between a few probes and the microbes gives each of hundreds of species a “fingerprint” response, much like how 10 digits can give everyone in the U.S. a unique phone number. The first aim of this project is to develop a new DNA signal amplification technique that allows fewer binding events to be detectable. This amplification strategy also lets signals be positive or negative, effectively allowing fingerprint signals to spread further apart. The enhanced incoherence of the sensors is known to be very helpful for compressed sensing. The second aim is to use new technologies in microfluidics to capture individual pathogen cells in very small droplets and acquire fingerprint signals from each droplet separately. By analyzing every droplet, this project pushes towards single-cell resolution which would enable its broader application in any task that demands the characterization of unknown microbes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

病原体的快速鉴定对于临床诊断和生物防御至关重要。如果得到及时的信息，临床医生可以开出更好的治疗方案，减缓耐药细菌的增加，美国的生物监测工作可以跟踪现有和新进化的病原体的出现和传播。虽然大多数快速诊断测试都有传感器，每个传感器都专门用于检测一种病原体，但这项研究正在开发新的DNA传感技术，只需几个传感器就可以有效地检测大量病原体。通过最大限度地减少必要的传感器数量，新的病原体监测设备可以是便携式的，并且对于日常使用来说是便宜的。该技术还提供了一种检测新出现的新型病原体的方法，而无需创建和部署新的检测试剂盒。除了进一步开发新的病原体识别技术外，该项目还开发了一个实践实验模块来探索这种方法，并在为莱斯大学本科生和研究生工程专业学生提供服务的生物传感和成像课程中实施。这项研究工作应用了压缩传感，它允许只有几个DNA探针（1）给每个物种一个指纹响应，（2）当同一样本中有几个病原体时，将这些指纹信号分离。压缩感知假设样本是稀疏的。稀疏性的出现是因为尽管可能有几十个或几百个可能的物种需要考虑，但来自患者或环境的任何单个样本都只有少数几个相关应用感兴趣的病原体。对于病原体检测，DNA探针各自与微生物物种多次结合。几个探针和微生物之间的结合事件的数量给了数百个物种中的每一个“指纹”反应，就像10个数字可以给美国的每个人一个独特的电话号码一样。该项目的第一个目标是开发一种新的DNA信号放大技术，允许更少的结合事件被检测到。这种放大策略还允许信号为正或负，有效地允许指纹信号进一步扩散。已知传感器的增强的非相干性对于压缩感测非常有帮助。第二个目标是使用微流体新技术在非常小的液滴中捕获单个病原体细胞，并分别从每个液滴中获取指纹信号。通过分析每个液滴，该项目推动了单细胞分辨率，这将使其在任何需要表征未知微生物的任务中得到更广泛的应用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。