EAGER: MEMS Enabled Real Time Detection of Pathogens Viruses and Biomarkers

几十年来，基于微悬臂梁的工具，如可变原子力显微镜，已经在纳米科学和技术领域得到了广泛和成功的应用。基于大量可用的实验结果和多个领域的专业知识，基于悬臂式系统通过对增加的质量做出响应来检测SARS-CoV-2病毒结合具有巨大的潜力。这一方法将使实时监测和处理新冠肺炎疫情成为可能，并将能够第一时间观察宿主的感染和传播情况。然而，除了技术挑战外，开发用于病原体检测的悬臂式设备还面临多个障碍，因为需要对目标病毒或生物标记物具有高度的选择性。为了变得实用，这些仪器需要一种使悬臂功能化的技术，使它们在空气和液体中稳定数小时。这将允许传感器实时工作，从而打破目前的病原体诊断范式。在这个项目中，PIS将开发现有微悬臂梁的这种功能化。他们将开发一种有选择地将抗体固定在活性悬臂表面的小间距固定方法。拟议的项目探索了材料和技术的功能驱动设计，以解决实时检测SARS-CoV-2等活跃病毒的问题。在本项目中开发的综合方法在为许多其他应用开发蛋白质/抗体涂层方面具有通用性和可转移性。此外，拟议的项目在目标应用中集成了材料合成、紫外线暴露/图案化、表征和性能评估，将为参与的研究生提供一个极好的教育平台，让他们体验微电子、生物化学和健康等交叉领域的各种挑战。具体地说，这些目标将通过结合荧光标记抗体溶液涂层和无掩膜紫外光诱导固定图案来实现，以确保活性病毒选择性地结合在悬臂梁上。PI的通用方法将包括应用不同类别的二苯甲酮类化合物自由基，这些自由基由紫外光产生，能够在分子水平上可靠地结合目标刺激蛋白的抗体。该项目的具体目标是鉴定和测试选择性固定在压阻性MEMS悬臂梁上的尖峰蛋白抗体的UV无掩模技术，以及优化检测系统的参数，以实现较短的检测时间和高灵敏度。为实现无噪声运行，将使用有源和基准压阻悬臂梁的特定应用阵列。为了确保通过亲和反应检测空气/气溶胶中的SARS-CoV-2病毒，将选择性地覆盖小间距图案，利用无掩膜紫外光诱导蛋白固定化抗体。具体地说，PIS将专注于优化悬臂的选择性功能化，与检测超小型病原体质量的新测量方法协同作用。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。

Micro-cantilever-based tools like variable Atomic Force Microscopies have been widely and successfully used in the field of Nano Science and Technology for decades. Based on vast available experimental results and expertise in multiple domains, there is a significant potential to use cantilever-based systems for detection of SARS-CoV-2 viruses binding by responding to the added mass. This approach will enable real time monitoring and handling the COVID-19 pandemic and will enable the observation of the infection and the transmission of the host for first time. However, the exploitation of cantilever devices for pathogen detection faces multiple hurdles, in addition to technical challenges, as high selectivity to the targeted virus or biomarker is required. To become practical these instruments need a technology for functionalization of the cantilevers that will make them stable in air and liquids for hours. This will allow the sensors to work in real time, thus breaking the current pathogen diagnostics paradigm. In this project the PIs will develop such functionalization of existing micro-cantilevers. They will develop a method for small pitch immobilization of antibodies selectively on the surface of the active cantilevers. The proposed project explores function-driven design of materials and technology to address the problem of real time detection of active viruses like SARS-CoV-2. The integrated approach developed in this project is versatile and transferable in developing proteins/antibody coatings for many other applications. Moreover, the proposed project, with its integration of material synthesis, UV exposure/patterning, characterization, and performance evaluation in the targeted applications, will serve as an excellent educational platform for participating graduate students to experience the full range of challenges in the cross-linking domains of microelectronics, biochemistry and health.Specifically, these goals will be achieved through the combination of coating of fluorescent tagged antibody solutions in combination with maskless UV photoinduced patterning for immobilization that ensures selective binding of active viruses on cantilevers. The versatile approach of the PIs will include application of different benzophenone class of compound radicals generated by UV light and capable of reliably binding the targeted spike protein’s antibody at the molecular level. Specific goals of this project are the identification and testing of UV maskless technology for selective immobilization of spike protein antibodies on piezoresistive MEMS cantilevers as well as optimizing the parameters of the detection system in order to achieve short detection time and high sensitivity. To achieve noise-free operation, application-specific arrays of active and reference piezoresistive cantilevers will be used. To ensure detection of SARS-CoV-2 viruses in air/aerosol by affinity reactions, small pitch patterns will be selectively coated, exploiting maskless UV photoinduced protein immobilization of antibodies. Specifically, the PIs will focus on the selective functionalization of the optimized cantilevers in synergy with novel measuring methods for detecting the mass of ultra-small pathogens.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.