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

基于微悬臂梁的工具，如可变原子力显微镜，在纳米科学与技术领域得到了广泛而成功的应用。基于大量可用的实验结果和多个领域的专业知识，使用基于悬臂的系统通过响应增加的质量来检测SARS-CoV-2病毒结合的巨大潜力。这种方法将实现对COVID-19大流行的实时监测和处理，并将首次观察到感染和宿主的传播。然而，除了技术上的挑战外，利用悬臂装置进行病原体检测还面临着多重障碍，因为需要对目标病毒或生物标志物具有高选择性。为了使这些仪器变得实用，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几个小时。这将使传感器能够实时工作，从而打破目前的病原体诊断模式。在这个项目中，pi将开发现有微悬臂的这种功能化。他们将开发一种选择性地在主动悬臂表面上小间距固定抗体的方法。该项目探索功能驱动的材料和技术设计，以解决实时检测SARS-CoV-2等活性病毒的问题。该项目开发的综合方法是通用的，可用于开发许多其他应用的蛋白质/抗体涂层。此外，该项目整合了材料合成、紫外线曝光/模式、表征和目标应用中的性能评估，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联领域的全方位挑战。具体来说，这些目标将通过将荧光标记抗体溶液的涂层与无掩膜UV光诱导模式相结合来实现，以确保活性病毒在悬臂梁上的选择性结合。pi的多功能方法将包括应用由紫外线产生的不同的二苯甲酮类化合物自由基，这些化合物自由基能够在分子水平上可靠地结合目标刺突蛋白的抗体。该项目的具体目标是鉴定和测试用于在压阻式MEMS悬臂梁上选择性固定刺蛋白抗体的UV无掩模技术，并优化检测系统的参数，以实现短检测时间和高灵敏度。为了实现无噪声操作，将使用特定应用的主动和参考压阻悬臂阵列。为了确保通过亲和反应检测空气/气溶胶中的SARS-CoV-2病毒，将选择性地包被小pitch模式，利用无掩膜UV光诱导的抗体蛋白固定化。具体来说，pi将专注于优化悬臂梁的选择性功能化，与用于检测超小型病原体质量的新型测量方法协同作用。该奖项反映了美国国家科学基金会的法定使命，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。

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.