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

Brown University, Providence RI

Investigators

Abstract

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.