This thesis presents an analysis of the signal-to-noise ratio in liquid core anti-resonant reflecting optical waveguides (ARROWs) and the application of hydrodynamic focusing to the waveguides. These concepts are presented as a method to improve the detection capabilities of the ARROW platform. The improvements are specifically targeted at achieving single molecule detection (SMD) with the devices. To analyze the SNR of the waveguides a test platform was designed and fabricated. This test platform was then used to examine relationship between the SNR and the location of the excitation region. It was determined that the excitation region should be moved closer to the solid-core. By moving the excitation region closer to the solid-core the distance the signal was required to travel in the hollow-core was reduced. This reduction led to a decrease in optical signal loss and resulted in a more than 2x increase in the SNR. Hydrodynamic focusing in the waveguides was developed as a method to increase the consistency of detection of the devices. In hydrodynamic focusing particles in the sample are forced towards the center of the waveguide with a buffer solution. With the particles focused to the center of the channel the percentage that passed through the excitation region can be increased improving the detection consistency of the device. ARROW chips designed for hydrodynamic focusing were simulated, fabricated, and preliminary testing was performed. Initial results have shown a more than 30% increase in particle focusing.