EAGER: Development of Surface Chemistry and Plasmonic Interferometers for Early-Onset Detection of Alzheimer Disease

该项目将开发新的表面化学和光学生物传感平台，以确定与阿尔茨海默病早期发病有关的脑组织损伤的生物标记物。将探索新的信号转导机制，以设计一种新的光学生物传感器，该传感器不太容易受到器件失调和外部噪声源的影响。这种新型生物传感器将用于检测一种与各种神经退行性疾病有关的生物标记物，包括阿尔茨海默病。拟议的转导传感机制的成功整合可以导致更可靠、更准确的护理点生物传感平台，这些平台有可能实现更快的药物筛选和发现，以及检测临床相关的生物标记物，用于疾病(如阿尔茨海默病)的早期筛查。相关研究人员将从最先进的生物传感技术培训机会中受益。研究和教育将通过课程开发将拟议的研究带入课堂，反过来将课堂体验带到实验室，让高中生、本科生、研究生和未被充分代表的群体成员参与提议的研究，使他们接触到边教边学的概念。拟议的项目将探索基于主动等离子体干涉和表面等离子激元(SPP)介导的嵌入式光发射器的荧光调制的新的表面功能化方法和转导机制，以开发高通量、多路复用的传感平台，具有更准确和可靠的光学响应，而不牺牲灵敏度。该项目的长期目标是实现高度集成的等离子体干涉仪，用于多路、可靠、便携式和高灵敏度的生物传感器。为了实现这一任务，拟议中的研究的短期目标是在血浆干涉仪的基础上开发和部署特定的表面化学，以检测髓样细胞2(TREM2)上表达的触发受体，TREM2是脑组织损伤的生物标记物，最近被认为与阿尔茨海默病的早期发病有关。此外，还将探索基于SPP介导的荧光调制的新型传输机制，在涂有嵌入式光发射器和电泵等离激元的有源等离子体干涉仪中，提高对外部高度准直和相干光源的关键要求，这将反过来提高基于等离子激元的光学生物传感器的可靠性和准确性。这项为期一年的探索性研究的具体目的如下：(I)开发用于特定探测TREM2的等离子体干涉仪手臂功能化的表面化学；(Ii)研究涂有薄层高效光发射体的有源等离子干涉仪的光学响应；(Iii)嵌入基于发射层的电泵浦等离子体源，如镶嵌在二氧化硅中的纳米硅或掺铒硅纳米晶体，以及用于直接激发SPP的金属/绝缘体/金属隧道结；(Iv)评估拟议用于TREM2探测的传感机制的灵敏度。展示基于等离子干涉测量的集成传感平台可以对从环境传感到医疗保健诊断的各个领域产生积极影响，并加快药物发现，例如阿尔茨海默病。参与该项目的学生和研究人员将获得广泛的实验和模拟技能，范围从纳米制造、光学设计和表征、器件集成和数值模拟。PI将指导所有参与该项目的学生。本科生(包括女性和代表性不足的少数族裔)和K-12公立学校的学生将分别从拟议研究和教学外展的子部分的研究经验中受益。该奖项反映了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。

This project will develop novel surface chemistry and optical biosensing platforms to a biomarker of brain tissue damage that has been associated with early onset of Alzheimer's disease. New signal transduction mechanisms will be explored to design a new class of optical biosensors that are less susceptible to device misalignment and external noise sources. The new class of biosensors will be used to detect a biomarker which is associated with various neurodegenerative disorders, including Alzheimer's disease. Successful integration of the proposed transduction sensing mechanisms can lead to more reliable, accurate, point-of-care biosensing platforms that have the potential to enable faster drug screening and discovery, and detection of clinically relevant biomarkers for early onset screening of disease (such as Alzheimer's). The involved researchers will benefit from training opportunities in state-of-the-art biosensing technologies. Research and education will be integrated by bringing the proposed research into the classroom via curricular development, and conversely bringing the classroom experience into the laboratory by involving high-school, undergraduate, graduate students and members of underrepresented groups in the proposed research, exposing them to the concept of learning by teaching.The proposed project will explore novel surface-functionalization methods and transduction mechanisms based on active plasmonic interferometry and surface plasmon polariton (SPP) mediated fluorescence modulation of embedded light emitters to develop high-throughput, multiplexed sensing platforms with more accurate and reliable optical response, without sacrificing sensitivity. The long-term aim of this project is to realize highly integrated plasmonic interferometers for multiplexed, reliable, portable biosensors with high sensitivity. To achieve this task, the short-term goal of the proposed research is to develop and deploy specific surface chemistry on top of plasmonic interferometers to detect Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), a biomarker of brain tissue damage that has recently been associated with early onset of Alzheimer's disease. Moreover, novel transduction mechanisms based on SPP-mediated fluorescence modulation in active plasmonic interferometers coated with embedded light emitters and electrically-pumped plasmon sources will be explored to lift the critical requirements for an external, highly collimated and coherent light source, which will, in turn, increase the reliability and accuracy of plasmon-based optical biosensors. The specific aims of this exploratory, year-long research are the following: (i) develop surface chemistry targeted to functionalize the arms of plasmonic interferometers for specific detection of TREM2; (ii) study the optical response of active plasmonic interferometers coated with thin layers of efficient light emitters; (iii) embed electrically-pumped plasmon sources based on emitting layers, such as silicon nanocrystals or erbium-doped silicon nanocrystals embedded in silicon dioxide, as well as metal/insulator/metal tunnel junctions for direct excitation of SPPs; (iv) assess the sensitivity of the proposed transduction mechanisms for TREM2 detection. Demonstration of an integrated sensing platform based on plasmonic interferometry can positively impact diverse fields, spanning from environmental sensing, to point-of-care diagnostics, and accelerate drug discovery, for Alzheimer's disease, for example. The students and researchers involved in this project will gain a broad set of experimental and simulation skills, ranging from nano-fabrication, optical design and characterization, device integration, and numerical simulations. The PI will mentor all students involved in the project. Undergraduate students (including women and underrepresented minorities) and K-12 public school students will benefit, respectively, from research experience on sub-sections of the proposed research and pedagogical outreach.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.