Development of Liquid-Phase Plasmonic Sensor Platforms for Biomedical Diagnostic Applications
Open Access DepositedLocalized surface plasmon resonance (LSPR) is an optical phenomenon influenced by local refractive index changes through the interaction between incident light energy and delocalized electrons in specific metal thin films, resulting in localized "hot spots." LSPR-based sensors, by leveraging these changes, offer advantages such as miniaturization, high sensitivity, cost-effectiveness, and the potential for use in point-of-care applications. In this thesis, LSPR-based nanohole arrays (NHAs) are developed as a sensing platform for near real-time, label-free monitoring of immobilized probe/target binding phenomena, facilitating the detection of low-level biomolecular target species crucial for biomedical diagnostics. Notably, NHAs can enable the capture of target molecules using surface-immobilized receptors, demonstrating the potential for various applications.Finite-difference time-domain (FDTD) simulations were employed to optimize the thickness of Au on NHA structures, followed by imaging using scanning electron microscopy (SEM). The sensing system comprises a portable spectrometer, optical fibers, probe station, microscope, light source, and a newly designed sensor chamber. To demonstrate liquid-phase sensor operation, a polydimethylsiloxane (PDMS) microfluidic channel was fabricated, allowing reflectance mode measurements from each NHA device sector. Surface functionalization involved the attachment of a polyethylene glycol (PEG) vi self-assembled monolayer, with bovine serum albumin (BSA) model protein attached to the PEG layer on Au surfaces as proof-of-concept for protein binding. In addition to BSA, the attachment of SARS-CoV-2 nanobody proteins to NHA surfaces was examined, demonstrating the versatility of the sensor platform for detecting various target molecules, including viruses. The development of LSPR-based sensing approaches involved surface functionalization and protein attachment, with characterization of these processes performed using X-Ray Photoelectron Spectroscopy (XPS). This dissertation presents the design, fabrication, and testing of NHA-based LSPR sensor platforms in a PDMS microfluidic channel, demonstrating their functionality and reproducibility in a liquid-phase environment, thereby making them suitable for detecting SARS-CoV-2 and other biomolecules relevant to biomedical diagnostics. The multidisciplinary approach, encompassing plasmonic nanomaterials, biochemical elements, microfluidic technology, and optical components, underscores the potential of this sensor platform for a wide range of applications. This thesis serves as a proof of concept for the sensor's performance, showcasing its validation through the attachment of two different proteins, BSA and SARS-CoV-2 nanobodies, thereby highlighting its potential for biomedical diagnostics through surface functionalization.
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