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

EAGER：开发表面化学和等离子干涉仪，用于阿尔茨海默病的早期检测

• 批准号: 1842605
• 负责人: Domenico Pacifici
• 金额: $ 10万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1842605&HistoricalAwards=false
• 关键词: EAGER; Development; Surface; Chemistry; Plasmonic

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.

该项目将开发新的表面化学和光学生物传感平台，用于与阿尔茨海默病早期发作相关的脑组织损伤的生物标志物。 新的信号转导机制将被探索，以设计一类新的光学生物传感器，是不太容易受到设备的不对准和外部噪声源。这种新型生物传感器将用于检测与各种神经退行性疾病（包括阿尔茨海默病）相关的生物标志物。所提出的转导传感机制的成功整合可以产生更可靠、更准确的即时生物传感平台，其有可能实现更快的药物筛选和发现，以及检测用于疾病（例如阿尔茨海默氏症）的早期发作筛选的临床相关生物标志物。参与的研究人员将受益于最先进的生物传感技术的培训机会。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，通过让高中生、本科生、研究生和代表性不足的群体成员参与拟议的研究，将课堂经验带入实验室，让他们接触从教学中学习的概念。建议的项目将探索新的表面-本发明涉及基于活性等离子体干涉测量和表面等离子体极化激元（SPP）介导的嵌入式光发射器的荧光调制的功能化方法和转导机制，以开发具有更准确和可靠的光学响应的高通量、多路复用传感平台，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，用于具有高灵敏度的多路复用、可靠、便携式生物传感器。为了实现这一任务，拟议研究的短期目标是在等离子体干涉仪上开发和部署特定的表面化学物质，以检测髓样细胞上表达的触发受体2（TREM 2），这是一种脑组织损伤的生物标志物，最近与阿尔茨海默病的早期发作有关。此外，将探索基于SPP介导的荧光调制的有源等离子体干涉仪中的新型转导机制，所述有源等离子体干涉仪涂覆有嵌入式光发射器和电泵浦等离子体源，以提高对外部高度准直和相干光源的关键要求，这反过来将提高基于等离子体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标如下：（i）开发表面化学，使等离子体干涉仪的臂功能化，以特异性检测TREM 2;（ii）研究涂有高效光发射器薄层的有源等离子体干涉仪的光学响应;（iii）嵌入基于发射层的电泵浦等离子体激元源，例如嵌入二氧化硅中的硅纳米晶体或掺铒硅纳米晶体，以及用于直接激发SPP的金属/绝缘体/金属隧道结;（iv）评估所提出的用于TREM 2检测的转导机制的灵敏度。基于等离子体干涉测量的集成传感平台的展示可以积极影响从环境传感到即时诊断的各个领域，并加速药物发现，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，包括纳米制造，光学设计和表征，器件集成和数值模拟。PI将指导参与该项目的所有学生。本科生（包括女性和代表性不足的少数民族）和K-12公立学校的学生将分别受益于拟议研究和教学推广的子部分的研究经验。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。