PFI-TT: The Development of Flow-Through Sensors for the Detection of Bladder Cancer in Urine Samples

PFI-TT：开发用于检测尿液样本中膀胱癌的流通式传感器

• 批准号: 1917902
• 负责人: James McGrath
• 金额: $ 24.94万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917902&HistoricalAwards=false
• 关键词: PFI; TT; Development; Flow; Through

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project concerns the benefits of non-invasively detecting cancer in small samples of accessible bodily fluids (blood, urine, saliva). All biofluids are abundantly populated with small sacs that express specific indicators (biomarkers) when cancer is present. The ability to sample biofluids and detect these indicators is the basis of the "liquid biopsy" concept. A liquid biopsy for blood could be incorporated into routine laboratory tests and catch cancer in its earliest stages where intervention is most impactful. A liquid biopsy in urine could be used to replace highly invasive procedures currently used to routinely surveil for recurrence of bladder cancer. This PFI-TT project seeks to hasten the arrival of routine cancer screening through liquid biopsy by fundamentally advancing the way biosensors are used in these assays to make them faster and more sensitive. Educationally, the project will train two talented post-graduate scientists in the key elements of technical entrepreneurship. The project will also maintain several opportunities for undergraduates to conduct academic research including programs supporting under-represented groups and individuals unlikely to otherwise be exposed to research in college. The proposed project will advance the concept of the liquid biopsy by developing flow-through sensors that detect cancer biomarkers on extracellular vesicles (EVs) in urine. Current biomarker detection schemes require the analyte to diffuse from the sample to the sensing surface, resulting in slow and often incomplete, responses. The project will emphasis a different paradigm where the sensor is built on a highly permeable membrane and EVs carrying the biomarkers pass through the membrane where they are captured and revealed through enzyme-based detection. The team will develop and optimize the chemistries for capture of biomarkers and development of signal on the ultrathin silicon nitride membranes with precision slit-pores. The team will also develop mathematical models of flow through slit-pore membranes and the EV capture process. Finally, the team will compare our experiments and models to results with diffusion-limited sensors. This will directly test the hypothesis that the flow-through configuration enables more sensitive and faster responding devices that can improve detection of cancer in liquid biopsies.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.

这种伙伴关系对创新 - 技术翻译（PFI-TT）项目的更广泛的影响/商业潜力涉及在可访问的体液（血液，尿液，唾液）的小样本中非侵入性检测癌症的好处。当存在癌症时，所有生物流体都有大量的小囊，这些小囊表达了特定的指标（生物标志物）。采样生物流体并检测这些指标的能力是“液体活检”概念的基础。可以将液体血液活检纳入常规实验室测试中，并在干预措施最具影响力的最早阶段捕获癌症。尿液中的液体活检可用于替代目前用于常规监测膀胱癌的高度侵入性手术。这个PFI-TT项目旨在通过从根本上推进这些测定法中生物传感器的方式来使其更快，更敏感的方式通过液体活检来加快常规癌症筛查的到来。在教育上，该项目将在技术创业的关键要素中培训两名才华横溢的研究生科学家。该项目还将为大学生开展学术研究的几个机会，包括支持代表性不足的群体和个人不太可能接受大学研究的计划。拟议的项目将通过开发流通传感器来提高液体活检的概念，这些传感器在尿液中检测到细胞外囊泡（EV）上的癌症生物标志物。当前的生物标志物检测方案要求分析物从样品到感应表面扩散，从而导致缓慢且通常不完整的响应。该项目将强调一种不同的范式，其中传感器建立在高度渗透的膜上，而携带生物标志物的电动汽车通过膜，通过基于酶的检测捕获并揭示了它们。该团队将开发并优化化学物质，以捕获生物标志物和具有精度缝隙pores的超薄硅膜上信号的发展。 该团队还将开发通过缝隙膜和EV捕获过程的流量数学模型。最后，团队将将我们的实验和模型与扩散限制传感器进行比较。这将直接检验以下假设：流通型配置可以使更灵敏，更快的响应设备可以改善液体活检中癌症的检测。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的审查标准通过评估来获得支持的。