EAGER: Nanoplasmonic Mesh SERS Sensors for in situ Spatiotemporal Monitoring of Biofilm Activities

多细胞系统中的生物活动，如微生物生物膜和癌性肿瘤，是异质的、动态的和适应性的。解决多细胞系统中复杂的时空生物过程对于生物学研究和医学应用至关重要。一个重要的挑战，有一个系统生物学的整体图景在于缺乏实时的时空生化表征方法的多细胞系统。本研究旨在开发一种创新的基于网格的生物传感器，以实现对多细胞系统（如微生物生物膜）中系统级生物活动的时空生化监测。该项目包括由弗吉尼亚理工大学可持续纳米技术中心协调的通过实验室参观和科学演示的推广活动，以吸引公众兴趣并促进生物传感主题的研究传播。此外，还将与工学多样性促进中心合作，通过面向农村地区K12学生的“想象夏令营”和面向录取女高中生的“女性预览周末”，促进STEM学术多样性。多细胞系统中的生物活动，如微生物生物膜和癌性肿瘤，是异质的、动态的和适应性的，通过不同的信号和调控途径由细胞相互作用协调。不幸的是，由于多细胞系统的侵入性，标准的生物分析方法不允许对多细胞系统进行原位时空生化监测。该项目开发了一种仿生微孔网格表面增强拉曼光谱（SERS）生物传感器，用于在多细胞生物膜系统中集成均匀的纳米等离子体热点阵列，并实现对系统级生物膜活动的原位时空SERS生化监测。本研究包括两个研究目标：(1)开发仿生纳米等离子体网状SERS生物传感器，在生物膜内整合大型均匀热点阵列，在非靶向分子分析和靶向pH传感中进行可靠的时空SERS测量；(2)在生物膜发育过程中和抗生素治疗后实现生物膜活性的原位时空SERS分子分析和pH传感。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。

Biological activities in multicellular systems, such as microbial biofilms and cancerous tumors, are heterogeneous, dynamic, and adaptive. Resolving complex spatiotemporal biological processes in multicellular systems is crucial for biology studies and medical applications. One of the significant challenges for having a holistic picture of systems biology lies in the lack of real-time spatiotemporal biochemical characterization methods for living multicellular systems. This research aims to develop an innovative mesh-based biosensor to allow spatiotemporal biochemical monitoring of system-level biological activities in multicellular systems, such as microbial biofilms. This project incorporates outreach activities through lab tours and science demos coordinated by the Virginia Tech Sustainable Nanotechnology center to engage public interest and promote research dissemination in biosensing topics. In addition, the team will collaborate with the Center for the Enhancement of Engineering Diversity to promote STEM academic diversity through the "Imagination Summer Camp" program for K12 students from rural areas and "Women's Preview Weekend" for admitted female high school students. Biological activities in multicellular systems, such as microbial biofilms and cancerous tumors, are heterogeneous, dynamic, and adaptive, coordinated by cellular interactions via different signaling and regulatory pathways. Unfortunately, standard bioanalysis methods do not allow in situ spatiotemporal biochemical monitoring of multicellular systems due to their invasiveness. This project develops a biomimetic microporous mesh-based surface-enhanced Raman spectroscopy (SERS) biosensor to integrate uniform nanoplasmonic hotspot arrays within multicellular biofilm systems and enable in situ spatiotemporal SERS biochemical monitoring of system-level biofilm activities. The research includes two research objectives: (1) develop biomimetic nanoplasmonic mesh SERS biosensors to incorporate large uniform hotspot arrays within biofilms for reliable spatiotemporal SERS measurements in nontargeted molecular profiling and targeted pH sensing, and (2) implement in situ spatiotemporal SERS molecular profiling and pH sensing of biofilm activities during biofilm development and after antibiotic treatment.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.