In this paper, old as well as new technological findings to decrease premature infant mortality are reviewed. This paper discusses fetal development throughout pregnancy from conception to full-term status as well as fetal lung development specifically from conception until full-term status. Several ideas to rapidly develop and mature fetal lungs are discussed such as mothers ingesting artificial surfactant supplements, either independently or coupled with antenatal corticosteroids, as well as intra-amniotic instillation prior to 28 weeks gestational. Drawbacks regarding these two are mentioned as well such as the fetus’s lungs not being mature enough to use the artificial surfactant leading into the idea of researching ways to rapidly develop fetal lungs, either week-by-week or stage-by-stage. Lastly, if the baby is born pre-maturely and is severely underdeveloped, research is currently being done on an artificial womb that the baby can be placed in to simulate a uterus where the fetus can develop on a normal timeline as he or she would in the mother’s womb.

A continuous flow, passive separation device was designed using an equivalent circuit to create variable flow rates for hydrodynamic focusing to drain channels and collection outlets. By varying the diameter of the sample inlet connection into the reservoir, the particle position was influenced significantly, which enabled desired separations. Additionally it was noted that the relative, horizontal position of the inlet also had a significant influence on particle position within the device. A dimensionless number, the Characteristic Sample Inlet, was developed to relate geometric properties of the inlet reservoir to downstream particle distribution. It was found that a 2:1 ratio between inlet reservoir and sample inlet diameter, and placed at the top of the reservoir yielded the best separation results. Fluid velocity profiles in the reservoir were explored using Comsol Multyphysics. The experimentally observed particle trajectories and COMSOL predictions were in good agreement. Based on Comsol models a dimensionless parameter to relate the unique velocity profiles within the inlet reservoir to downstream separation of particles was also developed. A mixture of 10, 5.5, and 3.0 µm particles were separated to three distinct collection outlets at 73.4%, 64.7%, and 52.8% respectively. Therefore this project shows that passive separations of particles can be achieved simply by alerting the ratio of inlet hole relative to inlet reservoir diameter, and by placing the inlet hole at the top of the reservoir.

ABSTRACT Implementation of Physiologic Pressure Conditions in a Blood Vessel Mimic Bioreactor System Kevin Mark Okarski Tissue engineering has traditionally been pursued as a therapeutic science intended for restoring or replacing diseased or damaged biologic tissues or organs. Cal Poly’s Blood Vessel Mimic Laboratory is developing a novel application of tissue engineering as a tool for the preclinical evaluation of intravascular devices. The blood vessel mimic (BVM) system has been previously used to assess the tissue response to deployed stents, but under non-physiologic conditions. Since then, efforts have been made to improve the vessel and bioreactor’s ability to emulate in vivo conditions. The ability to tissue engineer constructs similar to their native tissue counterparts is heavily reliant upon controlling the environment and mechanical stimuli the construct is exposed to. Mimicking physiologic conditions influences cellular growth, proliferation, and differentiation. Two important mechanical stimuli are cyclic strain and wall shear stress. Previous work sought to improve these factors within the BVM bioreactor and resulted in the implementation of pulsatile perfusion and increased fluid viscosity. These previous bioreactor design modifications generated pulsatile pressures of approximately 80 mmHg and a wall shear stress of 6.4 dynes/cm2. However, physiologic pressure waveforms were not achieved. Studies in this thesis were carried out to implement an effective means of establishing a more physiologic pressure wave within the bioreactor that is accurate, consistent, and easily adjustable. As a result of conducting the present studies, modifications to the bioreactor system were made that uphold the overall goals of efficacy and efficiency. The desired pressure wave was created by setting the degree of pump tubing occlusion on the 3-roller peristaltic pump head and using a water column to backpressure the bioreactor chamber. Maintaining a desired backpressure within the system necessitated the development of a new bioreactor chamber with increased extraluminal leak pressure resistance. The opportunity was also used to further improve upon the bioreactor chamber design to allow for 360° rotation to reduce cell sedimentation. Modifications to the bioreactor system required quantitative evaluation to assess their impact upon local flow dynamics to the tissue construct. A system model was created and evaluated using computational modeling. Through the work performed in this thesis, pulsatile pressure waves of approximately 120/80 mmHg were successfully established within the bioreactor. The ability to accurately model physiologic pressures will ultimately help yield tissue constructs more similar to native tissues – both healthy and pathological. The newly designed bioreactor chamber and computational model for the system will be helpful tools for implementing or evaluating future bioreactor developments or improvements. While the main objective of the thesis has been completed by creating a system capable of emulating physiologic pressure fluctuations, there still remains room for further improvements in back-pressuring and scaling the system, refining the rotational bioreactor chamber design, and building upon the complexity and accuracy of the computational model.

Heart failure is a common condition during which the pumping action of the heart is affected because the heart does not contract or relax properly. Heart failure affects about 5 million Americans, with 550,000 new cases diagnosed each year. Cardiac resynchronization therapy (CRT) is used to treat symptoms and other complications associated with a heart failure. While performing CRT, Implantation of a pacing lead in the left ventricle of the heart is a very challenging surgical procedure performed with fluoroscopy. The target location is often difficult to reach through the tortuous coronary venous anatomy, which varies greatly among individuals. Placement of the pacing lead is an important research topic because the ideal pacing location for some patients with heart disease may be the site of latest contraction in the left ventricle. The purpose of this project is to develop an algorithm to locate and track points on a lead in a sequence of images. The algorithm will track the motion of the points over time and generate displacement plots over time.

This project encompasses the design and development of a pretreatment microfluidic device for samples of physiological conductivity, namely a saline solution. The conductivity was reduced through the combination of dilution and ion removal using electric fields to enable downstream electro kinetic manipulations. The two major parts of this project include (1) designing a pretreatment protocol to reduce the conductivity of the sample solution to an acceptable level and (2) designing /fabricating a microchip that will effectively allow aim (1) to be performed on chip. This project is one of the first to observe the effects of an electric field, used in the application of ion removal, to reduce the conductivity of a sample. Through the combination of sample and low conductivity buffer, as well as the presence of an electric field, a conductivity pretreatment chip is created. Since biomarkers and analytes of interest are difficult to detect in complex raw samples, such as blood, this chip is a necessary preliminary step that allows for successive separations. Using previous literature from the field of capillary electrophoresis, a design and pretreatment protocol was developed to pretreat a sample into a target conductivity range. A PMMA device was fabricated using a laser photoablation system located on the Cal Poly campus. Off-chip electrodes were used to induce electrophoretic movement of ions across a membrane and out of the sample. The combination of dilution and electrical fields yielded samples that had their conductivity reduced 80%. Dilution was found to be more effective in a chip designed with a short process time and continuous flow. Ultimately, we wish to incorporate this device with other pre-fabricated pretreatment and electrokinetic devices to optimize certain bioseparations.

Filtration processes, whether on the microfluidic, clinical treatment systems, or industrial scale (e.g., point-of-care diagnostics, dialysis, and biopharmaceutical manufacturing, respectively), are often inseparable from membrane clogging (fouling). As a consequence, most, if not all, filtration systems require frequent maintenance to maintain functionality and efficiency. The thesis of this project hypothesizes that Dielectrophoresis can be combined with standard filtration to reduce filter fouling, extending membrane life, and enabling continuous operation. This project investigates a method to reduce fouling, add specificity and efficiency, and decrease the cost and challenge of filtration based biofluid separations. To substantiate this thesis, we designed, fabricated, and tested a filtration system to filter micron diameter particles in suspension using Millipore™ membranes together with fabricated electrodes in a cross-flow filtration system. This prototype device elicits a repulsive dielectrophoretic (DEP) force via the application of a direct current (5-20 volts) sourced from a computer controlled voltage sequencer, designed to levitate and remove larger particles (> 6 µm) before particulate-membrane interaction. Analysis of the results shows a sufficient decrease in particles adhered to the filtration membrane, as compared to control, suggesting DC DEP may be a valid effector in this device. We are convinced that further research will augment the results validating the proof-of-concept thesis presented herein.

Surgical Tooling Designed for the Direct Anterior Approach to Total Hip Arthroplasty Jon-Peter Meckel Total hip arthroplasty (THA) is becoming more and more common in the US as people continue to live longer and more active lives. The main reason that a THA is required is due to the “wear and tear” affliction of osteoarthritis, which in the year 2000 had at least 3% of the population over 30 showing symptoms. A revitalized approach to THA is the direct anterior approach, or Smith-Petersen approach, which limits the amount of musculature affected by the surgery and creates a very stable joint post-operatively. While this approach is showing great clinical success, it does require slightly unconventional patient positioning. The pioneers of this surgical approach include Dr. Joel Matta, who along with Mizuhosi (Union City, CA, USA) has created an impressive direct anterior approach surgical table to address the problems associated with getting patients in the right position. Unfortunately, this table is very expensive, gives no feedback on force application, and surgeons are being taught that it is required to perform the procedure. This thesis introduces a simple set of surgical tooling that facilitates the direct anterior approach very cost effectively, giving the surgeon the feedback lacking in the expensive Mizuhosi table, and the flexibility to attempt the approach without convincing his or her hospital to make such a large capital investment. A prototype was successfully developed and tested to show that a simple solution exists to make the direct anterior approach more feasible for surgeons to incorporate into their practice.

Thermal preconditioning to simulate shipping, handling and storage conditions did not affect distal tip stiffness values for permanently implantable cardiac leads used for pacing and defibrillation. Leads that were subjected to extreme temperatures and temperature cycling did not show changes in buckle force values compared with control specimens which were maintained at ambient room conditions. Absolute differences between all measurements were small, generally under 0.05 N and were attributable to measurement variability. Buckle force values are used to assess the propensity of leads to perforate the heart, a rare but potentially serious complication of implantable pacing and defibrillation systems. Since preconditioning and buckle force measurement methods have not yet been standardized and no published studies exist, it was unknown whether and how much thermal preconditioning could affect lead buckle force. This study involved eight lead models from all four major lead manufacturers and included both pacing and defibrillation leads spanning a range of materials and construction methods. The preconditioning parameters used in the study, such as temperatures and cycle times, were derived from current industry methods. Knowing whether thermal preconditioning is critical to perforation propensity allows lead manufacturers and regulators to more efficiently direct resources towards ensuring reliability as well innovation. The results of this study can also inform the AAMI working group which is developing industry standards for transvenous pacing and defibrillation leads.

<p>Current stabilization methods for periprosthetic fractures of the distal femur have been inadequate in achieving sufficient fixation and can lead to complications rates as high as 29%. Therefore, the overall objective of this study was to design, manufacture and evaluate (experimentally and computationally) a novel plating method for improving the treatment of periprosthetic fractures of the distal femur.</p> <p>Medial and lateral prototype plates were designed and manufactured based on the geometry of a synthetic femur and a femoral prosthesis. The two plates were linked via a compression screw and a small tab on each plate that inserts into pre-existing slots on the prosthesis to enhance rigidity of the construct. Synthetic femurs were used to assess the ability of the prototype plates to stabilize a periprosthetic fracture compared to a traditional single lateral plate. Each femur was subjected to a testing protocol that involved compressive and bending loading of the sample. The relative motion between the distal and proximal fragments during loading was then measured using both 2D and 3D motion tracking techniques. Both techniques revealed that the prototype bilateral plates were able to reduce motion of the fracture site compared to a single lateral plate.</p> <p>The final objective concerned the development of a finite element model to represent the experimental testing. The fracture gap motion obtained from the final model did not completely agree with the experimental data; however, additional experimental measurements found that the majority of these differences could be attributed to simplification made at the tab-slot interaction. Despite the difference, the model represents a significant step forward in the simulation of periprosthetic fracture treatment, and further refinement would allow for optimization of the plate design.</p> <p>Overall, the results of this thesis indicate that an alternative approach to treating periprosthetic fractures exists that is capable of improving fracture stabilization.</p> / Master of Applied Science (MASc)

Vocal folds are the twin in-folding of the mucous membrane stretched horizontally across the larynx. They vibrate modulating the constant air flow initiated from the lungs. The pulsating pressure wave blowing through the glottis is thus the source for voiced speech production. Study of vocal fold dynamics during voicing are critical for the treatment of voice pathologies. Since the vocal folds move at 100 - 350 cycles per second, their visual inspection is currently done by strobosocopy which merges information from multiple cycles to present an apparent motion. High Speed Digital Laryngeal Imaging(HSDLI) with a temporal resolution of up to 10,000 frames per second has been established as better suited for assessing the vocal fold vibratory function through direct recording. But the widespread use of HSDLI is limited due to lack of consensus on the modalities like features to be examined. Development of the image processing techniques which circumvents the need for the tedious and time consuming effort of examining large volumes of recording has room for improvement. Fundamental questions like the required frame rate or resolution for the recordings is still not adequately answered. HSDLI cannot get the absolute physical measurement of the anatomical features and vocal fold displacement. This work addresses these challenges through improved signal processing. A vocal fold edge extraction technique with subpixel accuracy, suited even for hard to record pediatric population is developed first. The algorithm which is equally applicable for pediatric and adult subjects, is implemented to facilitate user inspection and intervention. Objective features describing the fold dynamics, which are extracted from the edge displacement waveform are proposed and analyzed on a diverse dataset of healthy males, females and children. The sampling and quantization noise present in the recordings are analyzed and methods to mitigate them are investigated. A customized Kalman smoothing and spline interpolation on the displacement waveform is found to improve the feature estimation stability. The relationship between frame rate, spatial resolution and vibration for efficient capturing of information is derived. Finally, to address the inability to measure physical measurement, a structured light projection calibrated with respect to the endoscope is prototyped.