Nanoplasmonic On-Chip Immunoassay for Precision Immune Profiling

Abstract

A comprehension of the immune system is essential for precise prognosis and effective treatment of immune-related disorders. The practice of precision immune profiling is pivotal for personalized monitoring, disease progression tracking, and evaluating treatment efficacy, given the critical need for timely and accurate immune response monitoring across various diseases. However, challenges persist in precision immune profiling, including limited sample availability, complex immune interactions, and the management of high-dimensional data. This research focuses on the engineering and development of integrated nanoplasmonic on-chip immunoassays for precision immune signature profiling within microenvironmental settings. Specially synthesized nanoparticles are introduced into immunoassays to ensure sensitive and specific signals for immune profiling. Additionally, specially designed microfluidic channels enable high-throughput, multiplexed, in situ detection while creating a biomimetic cancer-immune microenvironment. Concurrently, machine learning-assisted approaches are employed to effectively analyze and interpret the resulting high-dimensional data. In the first project, a sandwich nanoplasmonic immunoassay is developed for precise immune profiling and subtyping of exosomes based on their PD-L1 expression levels. This approach generates a regime map to directly identify PD-L1 subtypes from real samples, offering a method for profiling cancer-related exosomal proteins or transmembrane proteins. In the second project, the integration of digital nanoplasmonic immunoassays with a hydrogel-embedded cell isolation microfluidic device enables on-chip visualization of exosomal-PD-L1-mediated communication between cancer cells and immune cells. This innovative setup provides in situ mapping and profiling of cell-to-cell communication within a microenvironment. In the third project, a soft pillars-based immunoassay, integrated with multiple types of nanoparticles, facilitates digital, real-time, in situ, multiplexed immune profiling within a microenvironment on-chip. The versatile microenvironment on-chip designs show promise for applications in complex cancer-immune microenvironment analyses, tumor organoid studies, and high-throughput single-cell analyses. The research demonstrates promising approaches in engineered nanoplasmonic immunoassays, holding significant potential as future clinical tools for monitoring cancer progression and as analytical tools for accurate and comprehensive immune system analysis.