Microfluidics refers to manipulation, precise control, and behavior of fluids at the micro and nanoliter scales. It has entered the realm of science as a way to precisely measure or mix small amounts of fluid to perform highly controlled reactions. Glass and polydimethylsiloxane (PDMS) are common materials used to create microfluidic devices; however, glass is difficult to process and PDMS is relatively hydrophobic. In this study, SU-8, an epoxy based (negative) photoresist was used to create various electrokinetic microfluidic chips. SU-8 is commonly used in microelectromechanical design. Spin coating of various SU-8 formulations allows for 1 μm to 100 μm thick layers with aspect ratios reportedly as high as 50:1. Case studies were performed to understand the curing/crosslinking process of SU-8 by differential scanning calorimetry. Supplier (MicroChem) recommended parameters were then altered to allow for adequate development of microfluidic channels, while maintaining enough molecular mobility to subsequently bond the SU-8 to a secondary substrate. Three SU-8 layers were used to create fully (SU-8) enclosed microfluidic channels. An (1) SU-8 2050 fully cured base layer was used as a platform on silicon to build from, (2) an SU-8 2050 partially cured layer for developing microfluidic channels , and (3) an SU-8 2007 uncured layer for bonding a secondary substrate to enclose the microfluidic channels. Bond quality was verified by optical and scanning electron microscopy, which resulted in a nearly 100% bond with little to no reflow of SU-8 into channels. Working pressures (ΔP across the capillary) of 15.57 lb/in2 (max detection) were obtained with no fluid leaks. Electroosmotic flow and steaming potential measurements failed. Electrophoretic behavior of glass particles was observed and particle velocities were compared by the application of 200 volts and 300 volts, across a channel length of 2 cm. Particle velocities obtained ranged from 100 μm/s to 1500 μm/s.

The purpose of this thesis was to demonstrate device functionality of 3-D paper-based, multiplex platforms, µPADs, without the use of coupling agents between layers. Previously, these platforms were fabricated with double-sided tape and cellulose powder to try to augment proper fluid routing, but difficulties with this method occurred. An acrylic housing unit with strategically placed pressure tabs was designed to aid horizontal and vertical fluid routing through the platform, thus eliminating the inconsistencies associated with coupling agents. Channel characterization studies, a COMSOLTM simulation, and development time studies were performed to aid device design and demonstrate device functionality. The implementation of this µPAD platform as a diagnostic instrument was validated via lateral flow immunoassays utilizing both biotinylated antibodies and biotinylated aptamers as capture reagents. Successful detection of the target analyte, IgE, as well as successful fluid routing through multiple layers of membrane was demonstrated by immunoassays performed on 3-D, multiplex platforms. Another important result determined the aptamers’ ability to detect IgE to be statistically the same as the antibodies’ ability; thus confirming aptamers as viable capture reagent alternatives to antibodies in lateral flow assays. Overall, this research project was performed to develop and validate via experiment a prototype paper-based microfluidic diagnostic device, µPAD, with the capability to detect multiple biomarkers on one platform.

A microfluidic reactor for synthesizing cadmium selenide (CdSe) quantum dots (QDs) was synthesized out of a silicon wafer and Pyrex glass. Microfabrication techniques were used to etch channels into the silicon wafer. Holes were wet-drilled into the Pyrex glass using a diamond-tip drill bit. The Pyrex wafer was anodically bonded to the etched silicon wafer to enclose the microfluidic reactor. Conditions for anodic bonding were created by exposing the stacked substrates to 300V at ~350oC under 5.46N of force. A syringe containing a room temperature CdSe solution was interfaced to the microfluidic reactor by using Poly (dimethylsiloxane) (PDMS) as an interface. The reactor was placed on a hot plate at 225oC, creating thermodynamic conditions for the QD chemical reaction to occur within the etched channels. Tygon® tubing transported solutions in and out of the microfluidic reactor. The CdSe solution was injected into the reactor by a syringe pump at an injection rate of 5 mL/hr, with a channel length of 2.5 cm. While in the microfluidic channels, QD residence time of approximately 30 seconds was sufficient enough for nucleation and growth of QDs to occur. The QD size was characterized by fluorescence full-width-half-maximum (FWHM), which is directly proportional to size distribution. The FWHM of the QDs synthesized was 38 nm, with a peak wavelength of 492 nm. By controlling combinations of pump rate and channel length, a range of QD sizes was able to be consistently synthesized through the microfluidic reactor with significant repeatability and reproducibility.

Some of the major obstacles the microfluidics industry has yet to overcome in order to facilitate large scale manufacturing of devices are costly back-end processes. Among these, bonding presents some of the most obvious difficulties and is often associated with structural deformation and surface modification. Off-stoichiometric thiol-ene (OSTE) is a relatively new material and hasn’t yet achieved the same level of adoption as Polydimethylsiloxane (PDMS) which has been the go-to material in the field of microfluidics for over two decades. OSTE offers an alternative to PDMS and promises bonding without surface treatment as well as a hydrophilic surface, removing a step in the manufacturing process. In this work, the property of OSTE to bond with a variety of commonly used thermoplastic materials were tested as well as its suitability for use in pharmaceutical devices such as Lab-on-a-chip. In addition to untreated OSTE, a surface modifier was used to examine the potential for surface modification when using OSTE as a microfluidics material. From the testing performed, we demonstrated OSTE’s capacity to form robust bonds with a range of thermoplastic materials as well as comparable biocompatibility to PDMS. / Bland de största hindren som industrin ännu ej löst när det kommer till storskalig produktion av mikrofluidiska produkter är kostsamma ”back-end” processer. Av dessa presenterar bindingsprocesser några av de mest uppenbara svårigheterna och medför ofta deformationer av finstrukturer samt ändringar i ytkemi. Off-stoichiometric thiolene (OSTE) är ett relativt nytt material och har ännu inte blivit lika utbrett i sin använding som Polydimethylsiloxane (PDMS) vilket har varit standardmaterialet i mikrofluidik i över två årtionden. OSTE erbjuder ett alternativ till PDMS, med bindingsprocesser som ej kräver ytterligare ytmodifikationer och en hydrofil yta, vilket eliminerar ett steg i tillverkningsprocessen. I detta arbete undersöktes egenskapen av OSTE att binda till en rad ofta använda thermoplaster samt dess lämplighet i medicinskt bruk, i system som ”Lab-on-a-chip”. Förutom obehandlad OSTE, så användes en ytmodifierare för att undersöka möjligheten för ytmodifiering vid användingen av OSTE i mikrofluidik. Resultaten av våra tester visade OSTE’s förmåga att forma robusta bindingar till en rad thermoplaster så väl som en jämförbar biokompatibilitet till PDMS.

Optofluidic flow-through biosensor devices have been in development for fast bio-target detection. Utilizing the fabrication processes developed by the microelectronics industry, these biosensors can be fabricated into lab-on-a-chip devices with a degree of platform portability. This biosensor technology can be used to detect a variety of targets, and is particularly useful for the detection single molecules and nucleic acid strands. Microfabrication also offers the possibility of production at scale, and this will offer a fast detection method for a range of applications with promising economic viability. The development of this technology has advanced to now warrant a descriptive model that will aid in the design of future iterations. The biosensor consists of multiple integrated waveguides and a microfluidic channel. This platform therefore incorporates multiple fields of study: fluorescence, optical waveguiding, microfluidics, and signal counting. This dissertation presents a model theory that integrates all these factors and predicts a biosensor design's sensitivity. The model is validated by comparing simulated tests with physical tests done with fabricated devices. Additionally, the model is used to investigate and comment on designs that have not yet been allocated time and resources to fabricate. Tangentially, an improvement to the fabrication process is investigated and implemented.

No description available.

Understanding cell migration is a key step in unraveling many physiological phenomena and predicting several pathologies, such as cancer metastasis. In particular, confinement has been proven to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical and spatial stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely the soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in vitro migration studies under spatial confinement in microfluidic device

Preterm birth is a global health challenge and the leading cause of neonatal mortality. Each year, about 15 million babies are born preterm globally. Traditional tools that have been exploited for the detection of preterm birth biomarkers are expensive, time consuming, or lack multiplexing capabilities. The work described in this dissertation highlights techniques developed to detect preterm birth biomarkers rapidly and accurately in the effort to mitigate preterm birth risk. In this dissertation, I first demonstrated the use of stereolithography digital light processing-based 3D printing and microfluidics for the development of microfluidic devices that had microvalves for fluid control. I then used these devices for microchip electrophoresis and fluorescence detection of five preterm birth biomarkers from a published panel. Next, I presented developments in 3D printed microchip electrophoresis device design. I separated amino acids and preterm birth biomarkers in a serpentine device design, obtaining good resolution, separation efficiency, and improved preterm birth biomarker peak capacity. Finally, I demonstrated the integration of solid-phase extraction with microchip electrophoresis in 3D printed microfluidic devices. These integrated devices enabled a seamless transition from preterm birth biomarker enrichment and labeling to microchip electrophoresis separation and fluorescence detection. The work described in this dissertation shows promise in advancing key tools needed to address preterm birth risk rapidly and effectively.

3D printing technology, which has its origins in rapid prototyping, is increasingly used to build functional devices. Although 3D printing technology has been well developed for thermoplastic polymers and metals, it is still in the research phase for soft polymeric materials such as silicones. Silicones are an industrially vital polymer characterized by a broad spectrum of chemical and physical properties for several smart applications, including on skin printing, smart sensors, multigradient material, and soft actuators. Extrusion-based multimaterial printing is one of the 3D printing techniques that have been adapted due to its compatibility to process silicone-based materials for constructing various functional devices. However, there are several challenges such as achieving on the fly mixing at low Reynolds numbers regime, achieving fast switching while using Newtonian/non-Newtonian inks, and achieving multimaterial printing on nonplanar surfaces. The development of suitable and robust printheads that are able to tackle those challenges can expand the application of this technology to a wide range of fields. In this thesis, several deposition-controlled printhead designs have been created for 3D printing multifunctional devices using an understanding of microfluidics. The established printhead can be controlled to formulate different multigradient structures through on the fly mixing during the material printing. Moreover, the developed printhead can be adapted to print multi viscous inks with high switching rates up to 50 Hz. Through the developed system, the printhead was able to track topologies in real-time, allowing objects to be printed over complex substrates. These new capabilities were applied to fabricate functional structures in order to demonstrate the potential of the developed printhead approaches that can be used in various applications, including smart sensors, soft robotics and multigradient objects. / Thesis / Doctor of Philosophy (PhD) / 3D printing techniques, such as extrusion-based multimaterial printing, have recently been utilized to process silicones due to their versatility in different smart applications, including multigradient material and soft actuators. Although it represents significant progress, there are still several challenges, including the proper mixing during printing with a laminar flow regime, the fast switching between different inks, and the printing over complex topographies. Therefore, various printhead designs have been developed in this thesis to tackle these challenges. In particular, a mixer printhead has been designed to allow mixing during printing for building multigradient objects. Also, a scalable printhead has been developed to allow fast switching for creating pixelated structures. Finally, a simple mechanical system has achieved multimaterial printing over various nonplanar surfaces. To the best of the author's knowledge, the developed printheads can be used in many fields, such as soft robotics and smart devices.

Advanced drug delivery systems have shown immense success through nanotechnology which overcomes the challenges posed by large sized particles such as poor solubility, bioavailability, absorption, and target-specific delivery. This study focuses on nano sizing by application of microreactor technology and nanoparticles to obtain polymeric particulate with a selection of model drugs for inhalation drug delivery routes. The development of nanoparticles of two challenging compounds in terms of solubility and permeability, namely Ibuprofen (IBU) and Salmeterol (SAL), was conducted using a continuous, controlled, and scalable system offered by microfluidic reactor with the incorporation of anti-solvent approach. The research explores the potential of this technology to enhance absorption rate and hence bioavailability of IBU via oral route, and SAL via inhalation. IBU, an anti-inflammatory drug, is classified as BCS Class II drug with low solubility and high permeability. SAL is a selective long acting β2-agonist which is co-dispensed along with a short-acting β2-agonist for quick relief of acute bronchoconstriction due to its long onset of action. This lack of the ‘kick’ effect in SAL can be attributed to its relatively higher lipophilicity which causes a delay in the diffusion to the β2 receptors on the smooth muscles. It is therefore feasible to assume that increasing the dissolution and/or diffusion rate of SAL in the interstitial fluids would reduce the delay between administration and the onset of action of this drug which would be beneficial to patients. Process and formulation parameters were investigated to optimize the production and stability of nano particles of both drugs using Y shaped microfluidic reactors. IBU results show that the smaller the angle between the two inlets were the smaller the particle size achieved. Moreover, the particle size increased with increasing the concentration of IBU solution. The effect of the polymer mixture ratio (PVP/HPMC) on the initial particle size was not clear though. The smallest particle size (113 nm) was achieved using 10° Y shaped chip with IBU concentration of 1 mg/mL and a polymer mixture of 0.3% w/v PVP and 0.5% w/v HPMC. Using a polymer mixture of 0.5% w/v of each polymer though yielded a better PDI (140nm and PDI of 0.5). Same observations were noted when the syringe pumps were replaced with a non-pulsatile pressure pump. Particle size though dropped significantly to 33nm. Stability data showed that all systems were practically stable regardless of the process or formulation parameters. In addition, a considerable 2.5 fold increase in dissolution rate was observed in the first 20 minutes when compared to the raw material. The optimized parameters were applied to SAL to produce nanocrystals with best result (59 nm) were obtained using 50µg/mL Salmeterol with microfluidics inlet angle 10° with non-pulse syringe pump. The stabilizing mixture was PVP 0.8% w/v and Tween 80 at a concentration of 0.02%. This approach offered a basis for the generation of nano sized SAL particles with higher fine particle fraction and better deposition in NGI than currently marketed formulations, thus providing a more efficient drug dose delivery and lung deposition.