California Polytechnic State University, San Luis Obispo is a university that encourages students to approach learning hands-on. As such, there is cutting-edge technology being developed by students in all departments on campus. Being that the university possesses an outstanding biomedical engineering department, there are groundbreaking medical devices that students are creating at Cal Poly SLO. These are devices that can better the lives of individuals suffering from ailments or fulfill needs in the medical industry. Subsequently, it is vital that these devices make it out of campus laboratories and into the hands of consumers. In order to move a product from ideation to the market, numerous steps must be completed and often times, especially with the challenges of commercializing medical devices, these efforts can result in failed product launches. As such, there is demand for a commercialization process to be created at Cal Poly SLO that will aid student created medical devices in reaching the market. This paper documents the progress made thus far on such a process at Cal Poly SLO.

The purpose of this thesis project was to demonstrate the ability to utilize the capabilities of aptamers so that they may act as capture reagents for paper microfluidic devices. Several characterization experiments were conducted as a precursor before the final experimentation was performed. Paper characterization, manufacturing protocols for printing and heating, as well as 3D chip fabrication were all performed and analyzed. The results confirmed that the control of fluid through a 3D microfluidic device based in nitrocellulose is possible. For the biochemistry portion of this thesis report, antibodies and aptamers were chosen to react with IgE, an antibody that is present in high concentrations in the urine of patients diagnosed with respiratory distress. Antibody chips were successfully created as a baseline lateral flow assay for comparison to new aptamer detector reagents. The aptamer experiments were able to demonstrate that it is possible to utilize the capabilities of aptamers so that they may behave as capture reagents in paper microfluidic devices. Overall, the experiments performed were extremely supportive of the ability to develop the field of paper microfluidics with the use of aptamers so that patient populations across the globe can be more accurately and effectively diagnosed.

Firearms are present in two-thirds of United States households. As of 2003, roughly 500,000 projectile wounds occur annually in the United States. This costs an estimated 2.3 billion dollars of medical spending. The best treatment of gunshot wounds relies heavily on experience, but even with experience the unpredictable nature of ballistics can make treatment difficult. Wound ballistics studies the injury pattern of a particular bullet. Ballistic gelatin tests are used to analyze this pattern. A block of 10 or 20% ballistic gelatin is set and a bullet is fired through the block. Key characteristics of the wound profile seen in this test include: depth penetration, permanent cavity, and temporary cavity. Even with ballistic gelatin tests, there is still confusion and many unknowns throughout wound ballistic literature. Finite element analysis (FEA) can be used to reproduce the wound profile of a ballistic gelatin test. A .38 lead round nose was chosen to model. The bullet was assigned as an elastic plastic material and the ballistic gelatin block was assigned as an elastic plastic and viscoelastic material. SolidWorks®, TrueGrid®, and LS-DYNA® were used to create the models. Two elastic plastic and two viscoelastic simulations were developed from these models. Elastic Plastic 2 and Viscoelastic 1 were able to reproduce a depth penetration, temporary cavity, and permanent cavity. Elastic Plastic 1 and Viscoelastic 2 were unable to reproduce the temporary cavity. These simulations provided hopeful results, but further investigation is needed for contribution to the advancement of bullet wound treatment.

Filtration is a technology that is used almost ubiquitously in society from uses raging from filtration of macroparticles from water to pharmaceutical grade filtration products to remove anything larger than a protein. However, with such a wide range of uses, most filtration products have the same issue; membrane clogging (fouling) that prevents continuous use and requires frequent maintenance. This thesis hypothesizes that by applying a direct current (DC) to an insulating array of posts, they will create a foul-less insulative dielectrophoretic filter (iDEP) that does not clog since particles will levitate above the insulating array. This thesis tested an inherited device (legacy device) and found that its design did not perform the desired foul-less filtration operation under the tested conditions. Therefore, using COMSOL simulations, the conditions of testing and improved deign were developed to fruition. These devices were fabricated and tested and found to successfully levitate yeast particles above the foul-less filtration array using a direct current insulative dielectrophoretic (iDEP) filter. Additionally, different post geometries were observed and how they affect the dielectric force on particles. Although a foul-less filter was not successfully developed over the course of this thesis, the groundwork for development of DC iDEP has been set.

Saccular aneurysms are the abnormal plastic deformation of veins and arteries that can lead to lethal thrombus genesis or internal hemorrhaging. Medication and surgery greatly reduce the mortality rates, but treatment is limited by predicting who will develop aneurysms. A common location for saccular aneurysm genesis is at the main middle cerebral artery (MCA) bifurcation. The main MCA bifurcation is comprised of the M1 MCA segment, parent artery, and two M2 segments, daughter arteries. Studies have found that the lateral angle (LA) ratio of the MCA bifurcation is correlated with aneurysm formation. The LA ratio is defined as the angle between the M1 and the larger M2 divided by the angle between the M1 and the smaller M2. When the LA ratio is equal to 1, perfectly symmetrical, no aneurysms are found at the MCA bifurcation. When the LA ratio is greater than 1.6, aneurysms are commonly found at the MCA bifurcation. In the research described here, varying MCA bifurcation angles were compared to uncover any changes to fluid flow and wall shear stress that could stimulate aneurysm growth. Eight pre-aneurysm MCA bifurcation models were created in SolidWorks® using 120 degrees, 90 degrees, and 60 degrees as the angle between the M1 and the larger M2. LA ratios of 1, 1.6 and 2.2 were then used to characterize the other branch angle (60 degrees with a LA ratio of 1 was excluded). These models were imported into COMSOL Multiphysics® where the laminar fluid flow module was used to simulate non-Newtonian blood flow. Fluid flow profiles showed little to no change between the models. Shear stress changed when the LA ratio was increased, but the changed varied between the 120, 90 and 60 degree models. 120 degree models had a 3.87% decrease in max shear stress with a LA ratio of 2.2 while the 90 degree models had 7.5% decrease in max shear stress with a LA ratio of 2.2. Each daughter artery had distinct areas of high shear stress when the LA ratio equaled 1. Increasing the LA ratio or decreasing the bifurcation angle caused the areas of shear stress to merge together. Increasing LA ratio caused shear stress to decrease and spread around the MCA bifurcation. The reduction in max wall shear stress for high LA ratios supports current aneurysm genesis hypothesizes, but additional testing is required before bifurcation geometries can be used to predicted aneurysm genesis.

3-D paper-based microfluidic devices (micoPADs) are small and portable devices made out of paper that offer a promising platform for diagnostic applications outside of a laboratory. These devices are easy to use, low cost, require no power source, and capable of detecting multiple targets simultaneously. The work in this thesis demonstrated the ability of a 3-D paper-microfluidic platform to simultaneously detect 5 targets. Rubber cord stock was used in conjunction with an acrylic housing unit to apply pressure along the edge of the channel. The indirect pressure application was successful in promoting vertical fluid flow between layers. Average channel development times were recorded between 110 seconds and 150 seconds. The implementation of the 3-D paper-microfluidic platform as a diagnostic device was validated with a colorimetric glucose assay. In a novel application, reagents were deposited onto the 3-D platform via a glucose reagent pencil created by Martinez et al. A visual signal was observed for the successful detection of glucose at a concentration of 1.2 mM. These results offer promise for future work in combing new reagent deposition techniques with a multi-layer paper-microfluidic platform. Overall, this research made advancements in the design of a paper-microfluidic platform capable of the simultaneous detection of 5 targets.

In the human genome, the SOST gene codes for a protein sclerostin. Sclerostin is an osteocyte-expressed negative regulator of bone formation. When the SOST gene is not coded, bone formation is reduced in individuals during skeletal maturation. This study utilizes nanoindentation methods to test for the mechanical properties of bones that both express and do not express the SOST gene. 100 transgenic murine femurs were obtained from Lawrence Livermore Labs in the form of 6 and 8 month SOST transgenic mice, 6 and 12 month SOST knockout mice, and wild type control littermates for each of the 4 age groups. Prior to nanoindentation the bones were broken in a previous experiment under three-point bending tests. Samples were embedded in epoxy and polished to a 0.05 micron level before indentation. Results showed significant difference amongst the treatment group effects for maximum load, hardness and elastic modulus. SOST KO mice had significantly higher values for these properties in comparison to the transgenic and wild type littermates. Additionally, side by side limb differences were examined in which there was a significant difference found amongst the treatment groups. Indentations were conducted in the 4 anatomical regions of each femur in expectation of examining any differences amongst them which resulted with no significant findings amongst them. Data from this study will support research which may result in potential new gene therapies targeted for the treatment of bone diseases such as osteoporosis.

The goal of this project is to eliminate electroosmotic flow (EOF) in a microfluidic chip. EOF is a naturally occurring phenomenon at the fluid-surface interface in microfluidic chips when an electric field is applied across the fluid. When isoelectric focusing (IEF) is carried out to separate proteins based on their surface charge, the analytes must remain in the separation chamber, and not migrate to adjacent features in the microfluidic chip, which happens with EOF. For this project, a microfluidic chip was designed and commissioned to be photolithographically transferred onto a Si wafer. A PDMS component was then casted on the Si wafer and plasma bonded to a glass substrate. This chip was initially designed to carry out continuous IEF, and the focus of the project was shifted to the analysis of eliminating EOF in a microfluidic chamber. Per previous research test methods, methylcellulose will be used to analyze the phenomenon of electroosmotic flow in the chamber. A COMSOL model is used a theoretical basis of comparison when analyzing the flow velocities of the treated versus untreated microfluidic chips. The purpose of this project is to use the research performed in on this chip as a precursor to future analyses of continuous IEF on microfluidic chips in the Cal Poly Microfluidics group.

A surrogate arm model was created that is capable of being used for oscillometry. This model is capable of being used as a bench top model for blood pressure cuff devices. The arm consists of endplates and internal supports that are 3D printed with ABS, a silicone rubber outer sleeve, and interchangeable arteries made from two silicone rubber strips glued together at the edges. The interchangeable arteries have varying compliances that can be used as different inputs for oscillometric testing. A process was established to measure the artery compliances with a curve fit correlation of 0.95. However, testing revealed that this artery compliance relationship might not be an accurate representation of the artery compliance while it is in the surrogate arm system. A blood pressure cuff was also used with the surrogate arm model to measure changes in artery volume. Testing with the surrogate arm revealed a blood pressure cuff was capable of measuring artery volume changes of 2mL to 8mL consistently within 3.28% error. Volume changes of 1mL were unable to be repeatable measured accurately with a blood pressure cuff.

To confirm computer simulations and Computational Fluid Dynamics (CFD) analysis, benchtop experiments are needed with a fluid that mimics blood and its viscoelastic properties. Blood is challenging to use as a working fluid in a laboratory setting because of health and safety concerns. Therefore, a blood analogue is necessary to perform benchtop experiments. Viscosity is an important property of fluids for modeling and experiments. Blood is a shear thinning fluid, so it has a decreasing viscosity with higher shear rates. This project seeks to create a blood mimicking fluid for benchtop laboratory use. Numerous fluids with different combinations of water, glycerin, and xanthan gum were created to mimic the shear thinning property of blood at different hematocrit levels. Since the amount of xanthan gum is very small, an analytical balance was used. To mix the solution, an immersion blender and a heat circulator were used. The data were obtained from 10-90 torque percent, which is the range over which the rheometer is accurate, so the exact ranges of shear rate tested depended on the test fluid. The created solutions were compared to blood at the equivalent hematocrit and previously performed tests.The three different equivalent hematocrits all produced results similar to viscosities of blood. The results were similarly representative of blood at different equivalent viscosities for the 0.0075% xanthan gum and the 0.075% xanthan gum by weight. The solutions were able to mimic the shear thinning behavior of blood at different equivalent hematocrits. The fluids with 0.075% xanthan gum and 50% water and 50% glycerin is a better representative than the fluids with 0.075% xanthan gum and 60% water and 40% glycerin.