Thesis (Ph.D.)--Boston University / The large electromagnetic field enhancement provided by nanostructured noble metal surfaces forms the foundation for a series of enabling optical analytical techniques, such as surface enhanced Raman spectroscopy (SERS), surface enhanced IR absorption spectroscopy (SEIRA), surface enhanced fluorescent microscopy (SEF), to name only a few. Critical sensing applications have, however, other substrate requirements than mere peak signal enhancement. The substrate needs to be reliable, provide reproducible signal enhancements, and be amenable to a combination with microfluidic chips or other integrated sensor platforms. These needs motivate the development of engineerable SERS substrate "chips" with defined near- and far-field responses. In this dissertation, two types of rationally designed SERS substrates - nanoparticle cluster arrays (NCAs) and SERS stamp - will be introduced and characterized. NCAs were fabricated through a newly developed template guided self-assembly fabrication approach, in which chemically synthesized nanoparticles are integrated into predefined patterns using a hybrid top-down/bottom-up approach. Since this method relies on chemically defined building blocks, it can overcome the resolution limit of conventional lithographical methods and facilitates higher structural complexity. NCAs sustain near-field interactions within individual clusters as well as between entire neighboring clusters and create a multi-scale cascaded E-field enhancement throughout the entire array. SERS stamps were generated using an oblique angle metal deposition on a lithographically defined piston. When mounted on a nanopositioning stage, the SERS stamps were enabled to contact biological surfaces with pristine nanostructured metal surfaces for a label-free spectroscopic characterization. The developed engineered substrates were applied and tested in critical sensing applications, including the ultratrace detection of explosive vapors, the rapid discrimination of bacterial pathogens, and the label-free monitoring of the enzymatic degradation of pericellular matrices of cancer cells.

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In this thesis, we have designed and optimized strip waveguide based micro-ring and micro-ring and micro-racetrack resonators for biosensing applications. Silicon-On-Insulator (SOI) platform which offers several advantages over other materials such as Lithium Niobate, Silica on Silicon and Silicon nitride is considered here. High index contrast enables us to miniaturize the biosensor devices and monolithic integration of source and detectors on the same chip. We have considered the dispersive nature of the waveguide and proceeded towards optimization. Finite difference schemes and Finite Difference Time Domain (FDTD) methods are the primary tools used to model the biosensor. Various structures such as channel waveguides and beam structures are analyzed on the basis of their suitability for sensing applications. Strip and Rib waveguides are the two geometries considered in our studies. In an optical guiding structure, effective index of the propagating optical mode can be induced by two different phenomena: i. Homogeneous Sensing In this category, effective index of a propagating optical mode changes with uniformly distributed analytes extending over a distance well exceeding the evanescent field penetration depth. The sample serves as the waveguide cover. ii. Surface Sensing In the case of surface sensing, analytes bound to the surface of the waveguide. The effective index of an optical mode changes with the refractive index as well as the thickness of an adlayer. A thin layer of adsorbed or bound molecules transported from liquid or gaseous medium serving as waveguide cover is referred as an adlayer. Both homogeneous and surface sensing schemes are addresses in this work. By bulk sensing method, the characteristics of bioclad covering the device are studied. Optimization of the resonator structure involves the analysis of following parameters: • Gap between the ring and bus waveguides • Free spectral range • Extinction ratio • Quality factor We have achieved a maximum bulk sensitivity of 115 nm / RIU with ring waveguide width of 450 nm and bus width of 350 nm which is better than an earlier reported value of 70 nm/ RIU. We have proposed a novel detection scheme consisting of a micro-racetrack resonator formed over a cantilever structure. The devoice works on the principle of opto-mechanical coupling to detect conformational changes due to biomolecular adherence. BSA (Bovine Serum Albumin) and IgG ( Immuno Globulin G) are the two proteins considered in the work. Mechanical analysis of the beam for tensile and compressive stresses and corresponding spectral responses of the racetrack resonators are analyzed both by semi-analytical and method and numerical analyzes. We compared various aspects of rib and strip waveguide racetrack resonators. We have proved by numerical simulation, that the device is capable of distinguishing tensile and compressive stress. Two strip waveguides of dimensions : 450 nm X 220 nm and 400 nm X 180 nm, former supporting both Quasi-TE and Quasi-TM modes where as the second configuration allows only Quasi-TE mode alone. Sensitivity of the cantilever sensor is : 0.3196 x 10-3 nm/ µɛ at 1550 nm wavelength.

<p dir="ltr">Ultra-scaled, always-on, smart, wearable and implantable (WI) therapeutic platforms define the research frontier of modern personalized medicine. The WI platform integrates real-time sensing with on-demand therapy and is ideally suited for real-time management of chronic diseases like diabetes. Traditional blood tracking methods, such as glucometers, are insufficient due to their once-in-a-while measurements and the imprecision of insulin injections, which can lead to severe complications. To address these challenges, researchers have been developing smart and minimally invasive microneedle (MN) components for pain-free glucose detection and drug delivery, potentially functioning as an "artificial pancreas". Inspired by natural body homeostasis, these platforms must be accurate and responsive for immediate corrective interventions. However, artificial MN patches often have slow readings due to factors like MN morphology and composition that remain poorly understood, hindering their optimization and integration into real-time monitoring devices. Despite extensive, iterative experimental efforts worldwide, a holistic framework incorporating the interaction between MN sensing and therapy with fluctuating natural body functions is missing. In this thesis, we propose a generalized framework for glycemic management based on the interaction between biological processes and MN-based operations. The results, incorporating theoretical insights from the 1960s and recent advancements in MN technology, are platform-agnostic. This generality offers a unique template to interpret experimental observations, justify the recent introduction of drugs like GLP-1 cocktails, and optimize platforms for accurate and fast disease management. </p>