As the microelectronics industry pushes microfabrication processes further, the lab-on-a-chip field has continued to piggy-back off the industry's fabrication capabilities with the goal of producing total chemical and biological systems on small chip-size platforms. One important function of such systems is the ability to perform single molecule detection. There are currently many methods being researched for performing single molecule detection, both macro and micro in scale. This dissertation focuses on an optofluidic, lab-on-a-chip platform called the ARROW biosensor, which possesses several advantages over macro-scale single molecule detection platforms. These advantages include an amplification-free detection scheme, cheap parallel fabrication techniques, rapid single molecule detection results, and extremely low volume sample probing, which leads to ultra-sensitive detection. The ARROW biosensor was conceived in the early 2000s; however, since then it has undergone many design changes to improve and add new functionality to the lab-on-a-chip; however, water absorption in the plasma enhanced chemical vapor deposited silicon dioxide has been a problem that has plagued the biosensor platform for some time. Moisture uptake in the oxide layer of the ARROWs leads to loss of waveguiding confinement and drastically decreases the overall sensitivity of the ARROW biosensors. New ARROW designs were investigated to alleviate the negative water absorption effects in the ARROWs. The new waveguide designs were tested for resiliency to water absorption and the buried ARROW (bARROW) design was determined to be the most successful at preventing negative water absorption effects from occurring in the PECVD oxide waveguides. The bARROWs were integrated into the full biosensor platforms and used to demonstrate high sensitivity single molecule detection without any signs of water absorption affecting the bARROWs' waveguiding capabilities. The bARROW biosensors are not only water resistant, they also proved to be the most sensitive biosensors yet fabricated with average signal-to-noise ratios around 80% higher than any previously fabricated ARROW biosensors.

The focus of this work is the integration of alkali vapor atomic vapor cells into common silicon wafer microfabrication processes. Such integrated platforms enable the study of quantum coherence effects such as electromagnetically induced transparency, which can in turn be used to demonstrate slow light. Slow and stopped light devices have applications in the optical communications and quantum computing fields. This project uses hollow core anti-resonant reflecting optical waveguides (ARROWs) to build such slow light devices. An explanation of light-matter interactions and the physics of slow light is first provided, as well as a detailed overview of the fabrication process. Following the discovery of a vapor transport issue, a custom capillary-based testing platform is developed to quantify the effect of confinement, temperature, and wall coatings on rubidium transport. A mathematical model is derived from the experimental results and predicts long transport times. A new design methodology is presented that addresses the transport problem by increasing the number of rubidium entry points. This design also improves chip durability and decreases environmental susceptibility through the use of a single copper reservoir and buried channel waveguides (BCWs). New chips are successfully fabricated, loaded, and monitored for rubidium spectra. Absorption is observed in several chips and absorption peaks depths in excess of 10% are reported. The chip lifetime remains comparable to previous designs. This new design can be expanded to a multi-core platform suitable for slow and stopped light experimentation.

The author presents the successful development of an on-chip, monolithic, integrated rubidium vapor-cell. These vapor-cells integrate ridge waveguide techniques with hollow-core waveguiding technology known as Anti-Resonant Reflecting Optical Waveguides (ARROWs). These devices are manufactured on-site in BYU's Integrated Microelectronic Laboratory (IML) using common silicon wafer microfabrication techniques. The ARROW platform fabrication is outlined, but the bulk of the dissertation focuses on novel packaging techniques that allow for the successful introduction and sealing of rubidium vapor into these micro-sized vapor-cells. The unique geometries and materials utilized in the ARROW platform render common vapor-cell sealing techniques unusable. The development of three generations of successful vapor-cells is chronicled. The sealing techniques represented in these three generations of vapor-cells include high-temperature epoxy seals, cold-weld copper crimping, variable pressure vacuum capabilities, indium solder seals, and electroplated passivation coatings. The performance of these seals are quantified using accelerated lifetime tests combined with optical spectroscopy. Finally, the successful probing of the rubidium absorption spectrum, electromagnetically induced transparency, and slow light on the ARROW-based vapor-cell platform is reported.

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.

Abstract Aim: The aim of this study was to investigate if treatment with “dry needling” in myofascial triggerpoints (MTrPs) in the rotatorcuff muscles may affect impingement symptoms such as pain during provocative tests, shoulder mobility, and function. The research questions were: Does the value of pain change on the Visual Analog Pain Scale (VAS) between before and after treatment? Do the positive provocative tests for impingement change between before and after treatment? Does the active shoulder mobility change between before and after treatment? Does the self-rated function change between before and after treatment? Method: The study was a prospective randomized intervention study and 19 persons with impingement symptoms (mean ± standard deviation; 58 ± 18 years, and shoulder pain duration 3.9 ± 1.6 months) were randomized into two groups. The groups were tested before, directly after and 3 weeks after treatment. The intervention group was treated twice, with a week in between, with “dry needling” in MTrPs. The control group was also treated on two occasions but was instead given a superficial needle in the infraspinatus muscle. All subjects were treated by the same physiotherapist. Pain was evaluated on the VAS when subjects performed active shoulder flexion before and after treatment. Provocative tests for shoulder impingement (Neer sign, Hawkins-Kennedy test and Jobe test) as well as range of motion tests were performed before, after and three weeks after treatment. The frequencies of positive/negative provocative tests were presented. Shoulder function was evaluated with the QuickDASH questionnaire. Significance level p≤0.05 was used in the study and a tendency was identified between 0.05 ≤ p &lt; 0.1. Results: There was a tendency (p=0.086) with decreased pain (VAS) in the intervention group after the treatment. Among the impingement tests only significant improved results was observed for Neer sign test three weeks after the treatment (p=0.025) No significant difference could be seen on the active shoulder mobility between before and after the treatment. The perceived function in the intervention group, measured with the Quick DASH questionnaire, showed a tendency (p=0.086) towards a better function. Conclusions: The study showed a tendency towards that”dry needling”  in MTrPs may affect impingement symptoms such as pain and function. The provocative tests for shoulder impingement, Neer sign, showed a significant decrease in pain after treatment. More studies with larger population is needed to make a statement about the effect of “dry needling” in MTrPs as a treatment for shoulder impingement symptoms. / Sammanfattning Syfte och frågeställningar: Syftet med studien var att undersöka om behandling med ”dry needling” (intramuskulär nålstimulering) i myofasciella triggerpunkter (MTrPs) i rotatorcuffmuskulaturen kan påverka impingementsymptom såsom smärta vid provokationstester, axelledsrörlighet och funktion. Frågeställningarna var: Förändras smärtskattning på visuell analog skala(VAS) vid aktiv axelflexion efter jämfört med före behandling? Förändras de positiva provokationstesterna för impingement efter jämfört med före behandling? Förändras den aktiva axelledsrörligheten efter jämfört med före behandling? Förändras den självskattade funktionen efter jämfört med före behandling? Metod: Studien var en prospektiv randomiserad interventionsstudie, 19 forskningspersoner (fp) med impingementsymptom, (medelålder 58 ± 18 år, besvärsdurationens medeltid 3.9 ± 1.6 mån), randomiserades till två grupper. Grupperna undersöktes före, direkt efter och tre veckor efter avslutad behandling. Interventionsgruppen behandlades vid två tillfällen, med en veckas mellanrum, med ”dry needling” i MTrPs medan kontrollgruppen vid två tillfällen istället fick en ytlig akupunkturnål i m infraspinatus. Behandlingen av alla fp utfördes av en och samma fysioterapeut. Smärta utvärderades med (VAS) vid aktiv axelflexion direkt före och efter behandling. Provokationstester (Neer sign, Hawkins-Kennedy test och Jobe test) samt rörlighetsmätning utfördes före, efter och tre veckor efter avslutad behandling. Frekvensen positiva/negativa provokationstesttest summerades. Funktionen utvärderades med frågeformuläret QuickDASH. Signifikansnivå p&lt; 0.05 används i studien och en tendens identifierades mellan 0.05 ≤ p &lt; 0.1. Resultat: Det fanns en tendens (p=0.086) till minskad smärta (VAS) i interventionsgruppen efter jämfört med före behandling. Bland impingementtesterna sågs enbart ett signifikant förbättrat resultat för Neers sign tre veckor efter avslutad behandling jämfört med före behandling (p=0.025). Ingen signifikant skillnad kunde ses gällande rörligheten före och efter behandling. Den upplevda funktionsförmågan mätt med frågeformuläret QuickDASH visade en tendens (p=0.086) mot bättre funktion i interventionsgruppen. Slutsats: Studien har visat tendenser på att ”dry needling” i MTrPs kan påverka impingementsymptom såsom minskad smärta och bättre självskattad funktion efter behandling jämfört med före. Impingementtestet Neer sign visade en signifikant minskad smärta efter behandling. Fler studier med större grupper, större ålderspann och längre behandlingstid behövs för att kunna uttala sig om effekten av ”dry needling” i MTrPs som behandlingsmetod vid impingementsymptom i axeln. / <p>Fristående kurs i Idrottsvetenskap inriktning idrottsmedicin 2013-2015</p>

This thesis presents rubidium packaging methods for integration using anti-resonant reflecting optical waveguides (ARROWs) on a planar chip. The atomic vapor ARROW confines light through rubidium vapor, increases the light-vapor interaction length, decreases the size of the atomic cell to chip scales, and opens up possibilities for waveguide systems on chips for additional optoelectronic devices. Rubidium vapor packaging for long-life times are essential for realizing feasibly useful devices. Considerations of outgassing, leaking and chemical compatibilities of materials in rubidium vapor cells lead to an all-metal design. The effect of these characteristics on the rubidium D2 line spectra is considered.

The rise of superbugs, including antibiotic-resistant bacteria, and virus outbreaks, such as the recent coronavirus scare, illustrate the need for rapid detection of disease pathogens. Widespread availability of rapid disease identification would facilitate outbreak prevention and specific treatment. The ARROW biosensor microchip can directly detect single molecules through fluorescence-based optofluidic interrogation. The nature of the microfluidic channels found on optofluidic sensor platforms sets some of the ultimate sensitivity and accuracy limits and can result in false negative test results. Yet higher sensitivity and specificity is desired through hydrodynamic focusing. Novel 3D hydrodynamic focusing designs were developed and implemented on the ARROW platform, an optofluidic lab-on-a-chip single-molecule detector device. Microchannels with cross-section dimensions smaller than 10 μm were formed using sacrificial etching of photoresist layers covered with plasma-enhanced chemical-vapor-deposited silicon dioxide on a silicon wafer. Buffer fluid carried to the focusing junction enveloped an intersecting sample fluid, resulting in 3D focusing of the sample stream. The designs which operate across a wide range of fluid velocities through pressure-driven flow were integrated with optical waveguides in order to interrogate fluorescing particles and confirm 3D focusing, characterize diffusion, and quantify optofluidic detection enhancement of single viruses on chip.

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.