Statistical data from clinical studies indicate that the death rate caused by heart disease has decreased due to an increased use of evidence-based medical therapies. This includes the use of magnetic resonance imaging (MRI), which is one of the most common non-invasive approaches in evidence-based health care research. In the current work, I present 3D Lagrangian strains and torsion in the left ventricle of healthy and isoproterenol-stimulated rats, which were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) imaging. With the implementation of the 12-segment model, a detailed profile of regional cardiac mechanics was reconstructed for each subject. Statistical analysis revealed that isoproterenol induced a significant change in the strains and torsion in certain regions at the mid-ventricle level. In addition, I investigated right ventricular cardiac mechanics with the methodologies developed for the left ventricle. This included a comparison of different regions within the basal and mid-ventricular regions. Despite no regional variation found in the peak circumferential strain, the peak longitudinal strain exhibited regional variation at the anterior side of the RV due to the differences in biventricular torsion, mechanism of RV free wall contraction, and fiber architecture at RV insertions. Future applications of the experimental work presented here include the construction and validation of biventricular finite element models. Specifically, the strains predicted by the models will be statistically compared with experimental strains. In addition, the results of the present study provide an essential reference of RV baseline evaluated with DENSE MRI, a highly objective technique.

Every year in the United States, an estimated 1.6 to 3.8 million people sustain sports-related traumatic brain injuries (TBIs), with an appreciable number of these injuries coming from the sport of softball. Several studies have analyzed the impact performance of catcher’s masks within the context of baseball; however, virtually no studies have been performed on fielder’s masks within the context of softball. Thus, the main objective of the present work was to evaluate the protective capabilities of softball fielder’s masks. To better understand the injury mechanisms and frequency associated with softball head/facial injuries, epidemiological data from a national database was reviewed first. Results displayed “struck-by-ball” as the most frequent injury mechanism (74.3%) for all head/facial injuries with a large majority occurring to defensive players (83.7%). With further motivation, the present work focused on testing the impact attenuation and facial protection capabilities of fielder’s masks from softball impacts. Testing with an instrumented Hybrid III headform was conducted at two speeds and four impact locations for several protective conditions: six fielder’s masks, one catcher’s mask, and unprotected (no mask). The results showed that most fielder’s masks reduced head accelerations, but not to the standard of catcher’s masks. On average, they reduced peak linear and angular acceleration from 40-mph impacts by 36-49% and 14-45%, respectively, while for 60-mph impacts they were reduced by 25-42% and 13-46%, respectively. Plastic-frame fielder’s masks were observed to allow facial contact when struck at the nose region at high speed. Observed differences in impact attenuation across fielder’s mask designs further suggested influence from specific design features such as foam padding and frame properties. Overall, the results clearly demonstrate that head/facial injuries may be mitigated through the broader use of masks, while further optimization of impact attenuation for fielder’s masks is pursued.

Micro-electro-mechanical systems (MEMS) technology has had an increasing impact on industry and our society. A wide range of MEMS devices are used in every aspects of our life, from microaccelerators and microgyroscopes to microscale drug-delivery systems. The increasing complexity of microsystems demands diverse microfabrication methods and actuation strategies to realize. Currently, it is challenging for existing microfabrication methods—particularly 3D microfabrication methods—to integrate multiple materials into the same component. This is a particular challenge for some applications, such as microrobotics and microfluidics, where integration of magnetically-responsive materials would be beneficial, because it enables contact-free actuation. In addition, most existing microfabrication methods can only fabricate flat, layered geometries; the few that can fabricate real 3D microstructures are not cost efficient and cannot realize mass production. This dissertation explores two solutions to these microfabrication problems: first, a method for integrating magnetically responsive regions into microstructures using photolithography, and second, a method for creating three-dimensional freestanding microstructures using a modified micromolding technique. The first method is a facile method of producing inexpensive freestanding photopatternable polymer micromagnets composed NdFeB microparticles dispersed in SU-8 photoresist. The microfabrication process is capable of fabricating polymer micromagnets with 3 µm feature resolution and greater than 10:1 aspect ratio. This method was used to demonstrate the creation of freestanding microrobots with an encapsulated magnetic core. A magnetic control system was developed and the magnetic microrobots were moved along a desired path at an average speed of 1.7 mm/s in a fluid environment under the presence of external magnetic field. A microfabrication process using aligned mask micromolding and soft lithography was also developed for creating freestanding microstructures with true 3D geometry. Characterization of this method and resolution limits were demonstrated. The combination of these two microfabrication methods has great potential for integrating several material types into one microstructure for a variety of applications.

The knee joint plays an essential role in the human musculoskeletal system. It has evolved to withstand extreme loading conditions, while providing almost frictionless joint movement. However, its performance may be disrupted by disease, anatomical deformities, soft tissue imbalance or injury. Knee disorders are often puzzling, and accurate diagnosis may be challenging. Current evaluation approach is usually limited to a detailed interview with the patient, careful physical examination and radiographic imaging. The X-ray screening may reveal bone degeneration, but does not carry sufficient information of the soft tissue conditions. More advanced imaging tools such as MRI or CT are available, but expensive, time consuming and can be used only under static conditions. Moreover, due to limited resolution the radiographic techniques cannot reveal early stage arthritis. The arthroscopy is often the only reliable option, however due to its semi-invasive nature, it cannot be considered as a practical diagnostic tool. Therefore, the motivation for this work was to combine three scientific methods to provide a comprehensive, non-invasive evaluation tool bringing insight into the in vivo, dynamic conditions of the knee joint and articular cartilage degeneration. Electromyography and inverse dynamics were employed to independently determine the forces present in several muscles spanning the knee joint. Though both methods have certain limitations, the current work demonstrates how the use of these two methods concurrently enhances the biomechanical analysis of the knee joint conditions, especially the performance of the extensor mechanism. The kinetic analysis was performed for 12 TKA, 4 healthy individuals in advanced age and 4 young subjects. Several differences in the knee biomechanics were found between the three groups, identifying age-related and post-operative decrease in the extensor mechanism efficiency, explaining the increased effort of performing everyday activities experienced by the elderly and TKA subjects. The concept of using accelerometers to assess the cartilage degeneration has been proven based on a group of 23 subjects with non-symptomatic knees and 52 patients suffering from knee arthritis. Very high success (96.2%) of pattern classification obtained in this work clearly demonstrates that vibroarthrography is a promising, non-invasive and low-cost technique offering screening capabilities.

In this study, a non-linear Finite Element (FE) model was created and analyzed to determine the pressure distribution between the residual limb and the prosthetic socket of a transfemoral amputee. This analysis was performed in an attempt to develop a process allowing healthcare providers and engineers to simulate the fit and comfort of transfemoral prosthetics to reduce the number of re-fittings needed for the amputees. The analysis considered the effects of interference due to insertion of the limb into the prosthesis, referred to as donning, and also the effects due to the body weight of the amputee. A non-linear finite element static implicit analysis method was utilized. This analysis implemented multiple finite element techniques, including geometric non-linearity due to large deflections, non-linear contacts due to friction between the contact surfaces of the residual limb and the socket, and non-linear hyper-elastic material properties for the residual limb’s soft tissue. This non-linear static analysis was carried out in two time-steps. The first step involved solving the interference fit analysis to study the pre-stresses developed due to the effect of donning. The donning process results in soft tissue displacement to accommodate the internal geometry of the prosthesis. In the second load application time-step, an additional load of half the person’s body weight was applied to the femur. The maximum normal stress (contact pressure) of 84 kPa was observed due to the combined effect of the donning procedure and body weight application, comparable to the studies performed by other researchers. The procedure developed through this work can be used by future researchers and prosthetic designers in understanding how to better design transfemoral prosthesis.

Lymph is primarily composed of fluid and proteins from the blood circulatory system that drain into the space surrounding cells, interstitial space. From the interstitial space, the fluid enters and circulates in the lymphatic system until it is delivered into the venous system. In contrast to the blood circulatory system, the lymphatic system lacks a central pumping organ dictating the predominant driving pressure and velocity of lymph. Transport of lymph via capillaries, pre-collecting and collecting lymphatic vessels relies on the synergy between pressure gradients, local tissue motion, valves and lymphatic vessel contractility. The direction of lymph transport is regulated by bicuspid valves distributed throughout pre-collecting and collecting lymphatic vessels. Effective transport of lymph into the venous system is of prime importance. Disruption of lymph transport, because of impaired lymphatic function, reduced numbers of vessels or valvular insufficiencies can have severe health consequences, including lymphedema for which current clinical therapies are not curative. The lymphatic valves are usually bicuspid, however, congenital malformations in the valve such as single leaflet valve formation and arrested lymphatic valve development are observed and can cause lymphedema. Here we employ 4-week-old mice to study the effects of valves and malformed valves on lymph transport shedding light into some of the potentially underlying consequences of lymphedema. Polyethylene glycol (PEG) coated latex particles were injected into the inguinal lymph node of anesthetized mice. Particle displacement measurements through efferent lymphatic vessels yielded velocity, wall shear stress, vorticity and strain of the efferent lymph flow field carrying lymph from subdermal inguinal lymph nodes. Lymphatic vessel endothelial Prox1 green fluorescent protein (GFP) marker enabled the detection of lymphatic vessel walls and valves. Flow field, flow velocity, flow rate, velocity profiles, wall shear stress, vorticity and strain values were compared in regions downstream of normal and malformed valves in two wild type mice. A Clec2-deficient mouse, which experiences lymphatic development defects and is used as a lymphedema model, was employed to further elucidate the lymphatic valves on transport. The absence of centralized pumping yields highly variable lymphatic flow cycles varying from one to fifteen seconds. The presence of lymphatic valves introduces boundary conditions that yield spatial and temporal flow gradients increasing the degree of complexity of lymph transport. The valves dictate the trajectory of the particles and promote the formation of recirculation zones. Even in the presence of valves, lymph flow commonly reverses. Congenital defects like a single leaflet valve lowers the lymph flow efficiency and promotes higher wall shear stress regions. Furthermore, the absence of functional valves in the Clec2-deficient mouse not displaying lymphedema yielded lymph flow lacking the pulsatility that characterizes normal lymphatic flow.

<div>Rare circulating cells are becoming a subject of interest due to their potential clinical applications to replace invasive procedures. Due their low presence in blood (as low as 1 in 1 ml of blood) various platforms are developed to capture and isolate them. Common limitations of current platforms include the inability to process large volumes of blood without an initial volume reduction step such as centrifugation, reliance on a single antibody for the capture, and the difficulty of releasing and retrieving the captured cells with high purity. A rare cell retrieval platform with high throughput operation and high purity retrieval is needed to capture these rare cells by processing large volumes of blood.</div><div><br></div><div>In this thesis study, we have developed a two-tiered microchip system to capture and retrieve rare cells from blood samples with high purity. The first module of the system is a high throughput microfluidic interface that is used to immunomagnetically isolate targeted rare cells from whole blood, and discard > 99.999% of the unwanted leukocytes. The second module is a microwell array that furthers the purification by magnetically guiding each cell into a separate well concurrently, and allows individual retrieval of each cell. Even though the system we have developed is applicable to many fields pertaining to rare cell capture, here we demonstrate the proof-of-concept using model cell lines that represent circulating fetal trophoblasts. We describe the design, operation as well as the experimental characterization of the system. Our characterization results show that the process can be completed within 145 minutes from the very beginning till the retrieval of a target cell, and can provide efficiencies and purities that are as high as 100%. </div><div><br></div><div>In order to demonstrate a real-world use case for our device, we present preliminary experiments done with blood samples from pregnant women. We show that we are able to retrieve candidate fetal cells under 167 minutes. Future work will be focused on sequencing the candidate fetal cells retrieved from maternal samples to confirm their fetal origin as well as enhancing system performance in maximizing the number of cells captured.</div><div><br></div>

<p>The extracellular matrix (ECM) plays a significant role in defining the mechanical properties of biological tissues. The proteins, proteoglycans, and glycosaminoglycans that constitute the ECM are arranged into highly organized structures (<i>e.g.</i> fibrils and networks). Cellular behavior is affected by the stiffness of the microenvironment and influenced by the composition and organization of the ECM. Mechanosensing of ECM stiffness by cells occurs at the fibrillar (mesoscale) level between the single molecule (microscale) and the bulk tissue (macroscale) levels. However, the mechanical behavior of ECM proteins at the mesoscale are not well defined. Thus, better understanding of the ECM building blocks responsible for functional tissue assembly is critical in order to recapitulate <i>in vivo</i> conditions. There is a need for the mechanical characterization of the ECM networks formed by proteins synthesized <i>in vivo</i> while in their native configuration. </p> <p>To address this gap, my goals highlighted in this dissertation were to develop appropriate experimental and computational methodologies and investigate the 3D organization and mechanical behavior of ECM networks <i>in situ</i>. The ECM of developing mouse tissues was used as a model system, taking advantage of the low-density networks present at this stage. First, we established a novel decellularization technique that enhanced the visualization of ECM networks in soft embryonic tissues. Based on this technique, we then quantified tissue-dependent strain of immunostained ECM networks <i>in situ</i>. Next, we developed mesoscale and macroscale testing systems to evaluate ECM networks under tension. Our systems were used to investigate tendon mechanics as a function of development, calculating tangent moduli from stress - strain plots. Similarly, we characterized ECM network deformation while uniaxially loading embryonic tissues, since this testing modality is ideal for fibril and network mechanics. Taken together, this information can facilitate the fabrication of physiologically relevant scaffolds for regenerative medicine by establishing mechanical guidelines for microenvironments facilitate functional tissue assembly.</p>

<p>  </p> <p>Cavitation, liquid slosh, and splashes are ubiquitous in science and engineering. However, these phenomena are not fully understood. Yet to date, we do not understand when or why sometimes the splash seals, and other times does not. Regarding cavitation, a high temporal resolution method is needed to characterize this phenomenon. The low temporal resolution of experimental data suggests a model-based analysis of this problem. However, high-fidelity models are not always available, and even for these models, the sensitivity of the model outputs to the initial input parameters makes this method less reliable since some initial inputs are not experimentally measurable. As for sloshing, the air-liquid interface area and hydrodynamic stress for the liquid slosh inside a confined accelerating cylinder have not been experimentally measured due to the challenges for direct measurement.</p>

Modern lower limb prostheses are devices that replace missing limbs, making it possible for lower limb amputees to walk again. Most commercially available prosthetic limbs lack intelligence and passive adaptive capabilities, and none available can adapt on a step by step basis. Often, amputees experience a loss of terrain adaptability as well as stability, leaving the amputee with a severely altered gait. This work is focused on the development of a semi-active damping system for use in intelligent terrain adaptive ankle prostheses. The system designed consists of an optimized hydraulic cylinder with an electronic servo valve which throttles the hydraulic fluid flowing between the cylinder’s chambers, acting on the prosthesis joint with a moment arm in series with a carbon spring foot. This provides the capability to absorb energy during the amputees gait cycle in a controlled manner, effectively allowing the passive dynamic response to be greatly altered continuously by leveraging a small energy source. A virtual simulation of an amputee gait cycle with the adaptive semi-active ankle design revealed the potential to replicate adaptive abilities of the human ankle. The results showed very similarly that irregularities in amputee biomechanics can be greatly compensated for using semi-active damping.