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

这一创新-技术转化伙伴关系(PFI-TT)项目的更广泛影响/商业潜力涉及在可获得的体液(血液、尿液、唾液)的小样本中非侵入性检测癌症的好处。当癌症出现时，所有的生物体液中都充斥着表达特定指标(生物标记物)的小囊。采集生物体液样本并检测这些指标的能力是“液体活组织检查”概念的基础。血液的液体活组织检查可以被纳入常规的实验室检测，并在干预最有效的早期阶段发现癌症。尿液活组织检查可以用来取代目前用于常规监测膀胱癌复发的高侵入性程序。这个PFI-TT项目寻求通过液体活检加速常规癌症筛查的到来，从根本上改进生物传感器在这些检测中的使用方式，使它们更快、更灵敏。在教育方面，该项目将在技术创业的关键要素方面培训两名有才华的研究生科学家。该项目还将为本科生保留几个进行学术研究的机会，包括支持代表不足的群体和个人，否则他们不太可能在大学里接触到研究。拟议的项目将通过开发流通式传感器来检测尿液中细胞外小泡(EVS)上的癌症生物标记物，从而推进液体活检的概念。目前的生物标志物检测方案需要分析物从样品扩散到传感表面，导致反应缓慢且往往不完整。该项目将强调一种不同的模式，即传感器建立在高度渗透的膜上，携带生物标记物的电动汽车通过膜，在那里它们被捕获并通过基于酶的检测揭示。该团队将开发和优化用于捕获生物标志物和在具有精密狭缝孔的超薄氮化硅薄膜上开发信号的化学物质。该团队还将开发通过缝隙孔膜的流动和电动汽车捕获过程的数学模型。最后，研究小组将把我们的实验和模型与扩散受限传感器的结果进行比较。这将直接检验这样一种假设，即直通式配置能够实现更灵敏和更快的响应设备，可以改进液体活检中的癌症检测。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.