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The rapid development of optofluidics, the combination of microfluidics and integrated optics, since its formal conception in the early 2000's has aided in the advance of single-molecule analysis. The optofluidic platform discussed in this dissertation is called the liquid core anti-resonant reflecting optical waveguide (LC-ARROW). This platform uses ARROW waveguides to orthogonally intersect a liquid core waveguide with solid core rib waveguides for the excitation of specifically labeled molecules and collection of fluorescence signal. Since conception, the LC-ARROW platform has demonstrated its effectiveness as a lab-on-a-chip fluorescence biosensor. However, until the addition of optical multiplexing excitation waveguides, the platform lacked a critical functionality for use in rapid disease diagnostics, namely the ability to simultaneously detect different types of molecules and particles. In disease diagnostics, the ability to multiplex, detect and identify multiple biomarkers simultaneously is paramount for a sensor to be used as a rapid diagnostic system. This work brings optofluidic multiplexing to the sensor through the implementation of three specific designs: (1) the Y-splitter was the first multi-spot excitation design implemented on the platform, although it did not have the ability to multiplex it served as a critical stepping stone and showed that multi-spot excitation could improve the signal-to-noise ratio of the platform by ~50,000 times; (2) a multimode interference (MMI) waveguide which took the multi-spot idea and then demonstrated spectral multiplexing capable of correctly identifying multiple diverse biomarkers simultaneously; and, (3) a Triple-Core design which incorporates excitation and collection along multiple liquid cores, enabling spatial multiplexing which increases the number of individual molecules to be identified concurrently with the MMI waveguide excitation. In addition to describing the development of optical multiplexing, this dissertation includes an investigation of another LC-ARROW based design that enables 2D bioparticle trapping, the Anti-Brownian Electrokinetic (ABEL) trap. This design demonstrates two-dimensional compensation of a particle's Brownian motion in solution. The capability to maintain a molecule suspended in solution over time enables the ability to gain a deeper understanding of cellular function and therapies based on molecular functions.

Nanopore technology has introduced new techniques for single particle detection and analysis. A nanopore consists of a small opening in a membrane on the nanometer scale. Nanopores are found in nature and are utilized for transporting molecules through biological membranes. Researchers have been able to mimic naturally forming biological nanopores and utilize them for a variety of sensing applications. Nanopores, fabricated either organically or inorganically, can be used for detecting biomarkers such as proteins, nucleic acids, and metabolites that translocate the membrane by way of the nanopore. Constant ionic current flow is measured through the nanopore by way of a sensitive ammeter. In the presence of a biomarker, the ionic current flow will be impeded, causing the electrical signal to drop. This drop uniquely corresponds to the type of particle passing through the nanopore. In this work, the thin membrane on which the nanopore resides is created through a newly developed meniscus shaped sacrificial technique. The sacrificial polymer material starts as a liquid and is confined to the microfluidic channel through the capillary effect, giving it the meniscus profile. It is used as a structural support on which a thin silicon dioxide layer is grown. The layer of oxide takes on the same natural meniscus shape as the sacrificial material. The polymer is subsequently etched, resulting in a hollow core liquid channel with a suspended meniscus membrane. This process allows a thin membrane to be fabricated on top of a microfluidic channel that ranges from 50-200 nm in thickness. The meniscus membrane is crucial to the success of nanopore formation. The nanoscale membrane allows for smaller, more precise nanopores to be created. Reduced nanopore dimensions are advantageous for the detection of smaller biomarkers. The platform described in this dissertation integrates solid-state naturally forming meniscus membranes with solid-core and optofluidic waveguides for nanopore detection applications. The waveguides allow for a particle trap to be introduced to the system. The ability to trap particles directly under the nanopore is critical to the speed of which the nanopore can operate. This dissertation focuses on the fabrication, characterization, and testing of an optofluidic platform that features a nanopore for rapid single molecule detection and analysis.