In this dissertation, advances in the fields of Photonics, and Plasmonics, and specifically, single cell analysis and waveguide sensing will be addressed. The first part of the dissertation is on Finite Difference Time Domain (FDTD) optimization and experimental demonstration of a nano-scale instrument that allows sensing at the cellular and subcellular levels. A new design of plasmonic coupler into a nanoscale waveguide is proposed and optimized using FDTD simulations. Following this, a subcellular nanoendoscope that can locally excite fluorescence in labelled cell organelles and collect the emitted fluorescent light for detailed spectrum analysis is fabricated and tested. The nanoendoscope has a sharp tapered tip of diameter ~ 50 nm that permits safe insertion into the cell that was confirmed by a number of viability experiments. FDTD analysis demonstrated that, with an optimized nanoendoscope taper profile, light emission and collection was very local. Thus, signal detection could be used for nano-photonic sensing of proximity of fluorophores. In further experiments, fluorescent signals were collected from individual organelles of living cells including: the nucleus of Acridine orange labelled human fibroblast cells, the nucleus of Hoechst stained live liver cells and the mitochondria of MitoTracker Red labelled MDA-MB-231 cells. In addition, this endoscope was inserted into a live organism, the nematode Caenorhabditis elegans, and in- vivo fluorescence signal was collected. Second, an innovative single step fabrication method of low loss polysilicon waveguides was developed as a potential platform for a number of photonic sensors. Optimization of a capacitively coupled plasma etching for the fabrication of a polysilicon waveguide with smooth sidewalls and low optical loss was demonstrated. A detailed experimental study on the influences of RF plasma power and chamber pressure on the roughness of the sidewalls of waveguides was conducted and waveguides were characterized using a scanning electron microscope. It was demonstrated that optimal combination of pressure (30 mTorr) and power (150 W) resulted in the smoothest sidewalls. The optical losses of the optimized waveguide were 4.1± 0.6 dB/ cm. Finally, an on-chip nanophotonic sensor for continuous blood coagulation analysis was proposed. The system was simulated using three-dimensional FDTD software. At first, the noise due to the presence of cells was calculated. Next, the design of a waveguide cladding-based filtering structure for elimination of the noise from cells was proposed and significantly decreased noise level was theoretically demonstrated.