This dissertation focuses on the development of biosensing platforms [assays] that could be potentially translated into point-of-care (POC) diagnostics for the monitoring of inflammatory and viral infections. The World Health Organization outlines the ASSURED criteria: Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end-users, as requirements for the development of effective POC diagnostics. The assays presented in this work were designed with these criteria in mind. Chapter 1 focuses on the components of POC test and strategies to improve the quality of the signal-to-noise ratio of the POC test. In Chapter 2, we developed immunoassays targeting interleukin-6 (IL-6). The chapter outlines IL-6’s value as a prognostic biomarker. To detect IL-6 with a broad dynamic range and high sensitivity, we employed a multilayered fluorescent assay that uses bioorthogonal chemistry and fluorescent-dye-doped silica nanoparticles. This configuration yields a broad dynamic range of 10 pM to 100 nM and a lower limit of detection of 2 pM compared to a traditional ELISA, which exhibits a dynamic range of 1 nM to 100 nM with a LOD of 1 nM. Chapter 3 details our work on monitoring dengue virus progression using both viral and host biomarkers. We developed a multiplex fluorescent immunoassay capable of detecting NS1 (a viral protein), and host-derived cytokines MCP-1 and IP-10. The primary focus of chapter 3 is the development of the MCP-1 assay. The assay achieved LOD of 4 pg/mL for MCP-1 in phosphate-buffered saline (PBS), and 43 pg/mL in serum, respectively. The dynamic range was from 100 pg/mL to 100 ng/mL. This platform offers a valuable strategy for clinical triage and disease staging in patients. Chapter 4 focuses on HIV detection through the quantification of capsid p24. We developed a site-specific conjugation strategy by remodeling Fc glycans and incorporating a sialic acid derivative modified with Tz, enabling bioorthogonal coupling to fluorescent nanoparticles without disrupting antibody function. Chapter 5 provides a comprehensive summary of the research. It also outlines the directions being pursued by current and future members of our research group. To illustrate our lab’s ongoing inno- vation, representative data from these future directions are included.