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，已经在纳米科学和技术领域广泛和成功地使用了几十年。基于大量可用的实验结果和多个领域的专业知识，有一个显着的潜力，使用基于荧光素酶的系统检测SARS-CoV-2病毒的结合，通过响应增加的质量。该方法将能够真实的实时监测和处理COVID-19大流行，并将首次观察感染和宿主传播。然而，除了技术挑战之外，用于病原体检测的悬臂装置的开发还面临多个障碍，因为需要对靶病毒或生物标志物的高选择性。为了实用，这些仪器需要一种技术来使杠杆功能化，使它们在空气和液体中稳定数小时。这将使传感器能够在真实的时间内工作，从而打破目前的病原体诊断范式。在这个项目中，PI将开发现有微杠杆的功能化。他们将开发一种方法，用于选择性地将抗体小间距固定在活性杠杆的表面上。拟议的项目探索功能驱动的材料和技术设计，以解决真实的实时检测活动病毒，如SARS-CoV-2的问题。在这个项目中开发的综合方法是通用的，可转移的蛋白质/抗体涂层开发许多其他应用。此外，该项目将材料合成、紫外线曝光/图案化、表征和性能评估整合到目标应用中，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。这些目标将通过荧光标记抗体溶液的涂层与用于固定的无掩模UV光诱导图案化的组合来实现，所述无掩模UV光诱导图案化确保活性病毒选择性地结合在抗体上。PI的通用方法将包括应用由UV光产生的不同二苯甲酮类化合物自由基，并且能够在分子水平上可靠地结合靶向刺突蛋白的抗体。该项目的具体目标是鉴定和测试用于在压阻式MEMS微悬臂梁上选择性固定刺突蛋白抗体的UV无掩模技术，以及优化检测系统的参数，以实现短检测时间和高灵敏度。为了实现无噪声操作，将使用有源和参考压阻式杠杆的特定应用阵列。为了确保通过亲和反应检测空气/气溶胶中的SARS-CoV-2病毒，将选择性地涂覆小间距图案，利用无掩模UV光诱导的抗体蛋白质固定。具体而言，PI将专注于优化杠杆的选择性功能化，与检测超小病原体质量的新测量方法协同。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。

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.