Transfemoral amputees around the world experience increased difficulty in climbing stairs due to lack of muscle, balance, and other factors. The loss of a lower limb greatly diminishes the amount of natural force generation provided that is necessary to propel oneself up stairs. This study investigated possible solutions to the problem of stair ascension for transfemoral amputees by the means of designing and developing an externally attachable device to a prosthesis. The number of amputations from military service has greatly increased since 2008, which shows there is a clear need for assistive devices (Wenke, Krueger, & Ficke, 2012). With the number of amputations rising and no current externally attachable products on the market to aid in stair ascension for transfemoral amputees, the need for this specific device has become more prominent. Research, previous work, and preliminary testing provided a basis for design and development of a new prototype. Bench top testing was conducted to review concepts in the prototype and provide data for further modifications. Results from testing of previous work, as well as testing of new concepts and modifications, provided a framework for designing a new externally attachable device for assistance in stair ascension. A new prototype was then designed, manufactured, and tested with bench models as well as real-time testing with amputees. Success of the device’s performance was based on bench top results and feedback from amputees, noting both the advantages and shortcomings of the new prototype. Testing provided results and feedback that the device was well built and functioned properly, but did not perform satisfactorily, particularly in the categories of force generation and balance.

As implantable medical devices are being used more often to treat medical problems for which pharmaceuticals don’t suffice, it is important to understand their interactions with commonly used medical modalities. The interactions between medical implants and Magnetic Resonance Imaging machines have proven to be a risk for patients with implants. Implanted medical devices with elongated metallic components can create harmful levels of local heating in a Magnetic Resonance Imaging (MRI) environment [1]. The heating of a biological medium under MRI is monitored via the Specific Absorption Rate (SAR). SAR, defined as power absorbed per unit mass (W/kg), can be calculated as , where σ is electrical conductivity of the medium in units of , |E| is the magnitude of the applied electric field in units of , and ρ is the density of the medium in units of . For continuous, uniform power deposition this can be measured experimentally as a rise in temperature over time (∆T/t), where c is the specific heat capacity of the medium in units of. To understand the SAR induced in-vivo, a phantom (Figure 2.10) is used to conduct in-vitro experiments, as it provides a controllable and repeatable experimental setup. In order to experiment in the phantom, an understanding of the background SAR distribution and in turn the exposure field distribution of the phantom is required as per the ASTMF2182-09 standard [2]. In this work, the background SAR distribution of an ASTM standard torso phantom is measured and studied via fiber optic thermometry. The measurements are compared with an electromagnetic model simulated via FDTD, demonstrating agreement between 10-25%. A custom exposure and data collection setup (including oscilloscope, function generator, RF amplifier, directional coupler, and Neoptix Omniflex Fiber Optic Thermometry system) was integrated and automated using NI LabView. The purpose of this thesis is to map the field distribution in a torso phantom under RF exposure from a 64 MHz MRI RF Birdcage, compare the results to an electromagnetic simulation, and finally conclude the accuracy of this method for field measurements in a standard torso phantom. Understanding the capabilities and accuracy of the fiber optic thermometry method will ultimately allow researchers to successfully apply this method to monitor background fields in their respective experimental setups (related to MRI implant heating) and understand its limitations.

Cerebral ischemia leading to an ischemic stroke is a possible complication of a transcatheter aortic valve replacement (TAVR) procedure. This is because embolic debris can become dislodged and travel through the aortic arch, where they either continue to the descending aorta and join the systemic circulation or travel into the cerebral vasculature through the three daughter vessels that branch off the top of the aortic arch. These three vessels are the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. These three vessels lead either directly or indirectly to the cerebral vasculature, where the diameter of vessels become very small. If a large enough embolus travels into the cerebral vasculature, it can become stuck in the small cerebral vessels, blocking blood flow and cutting off the supply of oxygen to brain cells. The purpose of this study is to expand upon previous work in order to 1) create a more accurate physics simulation of blood and debris flow through the aortic arch 2) report on embolic debris distribution through the aortic arch and 3) analysis on which physical parameters affect embolic debris distribution. The physical parameters analyzed were particle diameter and particle density. This study was performed by creating a finite element model in COMSOL Multiphysics™ using a SolidWorks model of an aortic arch, with dimensions taken from a patient’s CT scan. Computational fluid dynamics was performed using a pulsatile pressure waveform throughout the aortic arch with a non-constant viscosity model. Once the velocity profile through the aortic arch matched with value ranges from literature, the particle tracing study was implemented. Both a pulsatile pressure waveform and a constant pressure model were analyzed, as well as a constant viscosity model and a non-constant viscosity model. The pulsatile pressure waveform influenced particle distribution and is recommended for future studies since this model leads to pulsatile flow, which is representative of flow through the aorta. It was seen that the non-constant viscosity model did not have a large effect on the velocity profile, but more than doubled the surface average value of viscosity. It also had an effect on the particle distribution through the aortic arch. Small diameter emboli were more likely to flow into the descending aorta, the brachiocephalic artery, and the left subclavian artery; larger emboli were more likely to flow into the left common carotid. Lower density emboli were more likely to flow into the descending aorta and the brachiocephalic artery. Averaging all densities and sizes, it was determined 44.8% of emboli flow into the three daughter vessels, but ultimately only 30.61% of emboli flow into the cerebral vasculature and have the potential to cause an ischemic stroke.

Blood flow velocity is an important parameter that can give information on several pathologies including atherosclerosis, glaucoma, Raynaud’s phenomenon, and ischemic stroke [2,5,6,10]. Present techniques of measuring blood flow velocity involve expensive procedures such as Doppler echocardiography, Doppler ultrasound, and magnetic resonance imaging [11,12]. They cost from $8500-$20000. It is desired to find a low-cost yet equally effective solution for measuring blood flow velocity. This thesis has a goal of creating a proof of concept device for measuring blood flow velocity. Finger blood flow velocity is investigated in this project. The close proximity to the skin of the finger’s arteries makes it a practical selection. A Red Green Blue (RGB) color sensor is integrated with an Arduino Uno microcontroller to analyze color on skin. The initial analysis involved utilization of red RGB values to measure heart rate; this was performed to validate the sensor. This test achieved similar results to an experimental control as the measurements had error ranging from 0% to 6.67%. The main analysis was to measure blood flow velocity using 2 RGB color sensors. The range of velocity found was 5.20cm/s to 12.22cm/s with an average of 7.44cm/s. This compared well with the ranges found in published data that varied from 4cm/s to 19cm/s. However, there is an error associated with the device that affects the accuracy of the results. The apparatus has the limitation of collecting data between sensors every 102-107ms, so there is a maximum error of 107ms. The average finger blood flow velocity of 7.44cm/s may actually be between 6.17cm/s and 9.39cm/s due to the sampling error. In addition, mean squared error analysis found that the most likely time difference between pulses among those found is 739ms, which corresponds to 5.21cm/s. Although there is error in the system, the tests for heart rate along with the obtained range and average for finger blood velocity data provided a method for analyzing blood flow velocity. Finger blood velocity was examined in a much more economical manner than its traditional methods that cost between $8500-$20000. The cost for this entire thesis was $99.66, which is a maximum of 1.17% of the cost.

Colorectal cancer is the second most common cause of cancer-related deaths in the United States, with the relative 5-year survival rate for distant stage cancer being only 14%. The most common treatment for colorectal cancer is with chemotherapeutic drugs; however, the discovery of these drugs is costly, time-consuming, and often requires the use of animal models that do not yield results that translate to clinical trials. Due to these shortcomings, researchers seek to develop physiologically relevant in vitro tumor models that more accurately mimic the tumor microenvironment for cheaper and faster high-throughput drug screening. The aim of this research was to develop a colorectal cancer tumor model co-cultured with endothelial and stromal cells, followed by validation with clinically relevant chemotherapeutic agents within microfluidic devices. The first experiment consisted of a lipofection of fibroblasts to yield fluorescently tagged cells that could be later imaged using a fluorescence microscope. The next experiment consisted of a co-culture of tumor, endothelial, and fibroblast cells at varying densities in a twodimensional (2D) culture to determine the optimal plating densities that would yield quantifiable tumor and endothelial network formation. The following experiment used these optimal densities to test the effects of the chemotherapeutic agents oxaliplatin and SN38 on the tumor and endothelial cells in 2D. After the various densities and drug concentrations were tested in 2D, the model was introduced into microfluidic devices. The first experiment in the devices was similar to the first experiment plated in 2D, as it involved the establishment of optimal plating densities of all three cell types within the devices. Similarly, the goal of this experiment was to yield quantifiable tumor and endothelial network formation within the devices. The final experiment performed in this research was the introduction of oxaliplatin and SN38 to the optimized densities v of cells determined from the previous experiment, with the aim of evaluating the effects of these chemotherapeutic agents on the tumor and endothelial cells within microfluidic devices. The two experiments plated in 2D established plating densities to be tested in the devices. These experiments also showed that increasing drug concentrations resulted in reduced tumor count and size and revealed no disruption in the endothelial networks when exposed to oxaliplatin concentrations as high as 50 µM. The final two experiments in microfluidic devices revealed that endothelial network formation is not yet possible within the devices with the current protocols, but that tumor cells still showed dose-dependent responses to drug exposure as they did in 2D. Due to the lack of network formation in this device model, future work is required to allow for endothelial cell organization into networks, to further increase the physiological relevancy of this model to in vivo tumor conditions.

<p>Microinjection is an established and reliable method to deliver transgenic constructs and other reagents to specific locations in the animal. Specifically, microinjection of a desired DNA construct into the distal gonad is the most widely used method to generate germ-line transformation of <em>C. elegans</em>. Although, current <em>C. elegans</em> microinjection method is an effective manner for creating transgenic worms, it requirements such as expensive multi DOF micromanipulator, detailed injection alignment procedure and skilled operator which makes the microinjection process slow and not suitable for scale to high throughput. Although many microfabricated microinjectors exist, none of them are capable of immobilizing a freely mobile animal such as <em>C.elegans</em> worm. In this research, a microfluidic microinjector was developed to simultaneously immobilize a freely mobile animal such as <em>C.elegans</em> and perform microinjection by using a simple and fast mechanism for needle actuation. The entire process of the microinjection takes ~30 seconds which includes 10s for worm loading and aligning, 5s needle penetration, 5s reagent injection and 5s worm unloading. The capability of the microinjector chip for creating transgenic <em>C. elegans</em> was illustrated (with success rate between 4% to 20%)</p> / Master of Science (MSc)

The product of this thesis aims to enable the study of the biochemical and physical dynamics of the lower limbs at high levels of muscle tension and fast contraction speeds. This is accomplished in part by a magnetic resonance (MR) compatible ergometer designed to apply a load as a torque of up to 420 Nm acting against knee extension at speeds as high as 4.7 rad/s. The system can also be adapted to apply the load as a force of up to 1200 N acting against full leg extension. The ergometer is designed to enable the use of magnetic resonance spectroscopy and imaging in a three Tesla Siemens Skyra MRI system. Due to the electromagnetic limitations of having the device operate inside the magnet, the design is split into two components. One designed to fit inside the 70 cm bore of the scanner. This component is electromagnetically passive; made out of materials exhibiting minimal magnetic interference, and having no electrically powered parts. The other component is electromagnetically active; it contains all of the powered elements and actuates the passive part from another room. A tensioned cable transmits power through a waveguide; a pipe through the wall of the MRI room with an RF shield. The device was tested applying a sagittal plane moment on the knee joint during isometric, isokinetic, isotonic, and constant power contractions.

Ion sensitive field effect transistors (ISFETs) are semiconductor sensors that have the capability to determine the selected concentration of a specific ion in a solution. Most modern ISFETs utilize their ion selective properties for glucose monitors for diabetics. However, in this thesis, the ISFET fabricated is for the selective detection of K+. The goals of this thesis are to develop a functioning ion-selective polymer membrane, manufacture a working FET device, and implement the two aspects together into a working bench-top K+ selective ISFET device. Properties of a polymer composed of 33 wt.% polyvinyl chloride (PVC) 66 wt.% dioctyl sebacate (DOS) and 1 wt.% valinomycin applied to an ion-sensitive electrode (ISE) were investigated. The membrane generated a sensitivity value of -9.864E-08 Ω/log10(CK). Though this data set was affected by both the maximum resolution of the I-V curve tracing device and the thin-membrane effect. Selectivity tests following the IUPAC two-solution method in the presence of Na+ as the interfering ion, provided selectivity values of 0.228 and 0.443 with higher ratios of primary ion to interfering ion resulting in higher selectivity coefficients. Additionally, utilizing an illumination test, dielectric constants of 17.71 and 10.88 were calculated dependent on the amount of solvent used during formulation. Fabrication of the FET device also resulted in developments in metal contact materials, nitride film processing, and physical vapor deposition (PVD) processes. With further improvements, it is possible to fabricate a biocompatible, wearable K+-selective monitor for continuously testing dialysis patients.

Snoring is a sleep disruption that can lead to obstructive sleep apnea (OSA), which interrupts breathing by obstructing the airway. Injecting a protein crosslinker, such as genipin, into the soft palate could decrease the severity of snoring and OSA by stiffening the soft palate. Equine soft palates modeled human palates due to a high incidence of awake snoring and apnea. The pilot in vivo study treated six horses with two 100 mM injections of the buffered genipin reagent. The efficacy phase horses underwent respiratory audio recordings to document snoring changes using Matlab and ImageJ in the time and frequency domains. Histological analysis was completed on the safety phase palates post treatment. All horses were successfully treated with the genipin injections. At least one horse showed high frequency amplitude reductions, and all horses had low frequency amplitude reductions, correlating to a reduction in palatal displacement and snoring loudness. One efficacy horse appears to have been completely cured. The histological analysis presented tissue damage, mucosal tissue damage, and mild inflammation due to palate expansion and errant injections. Different injection volumes and techniques should be investigated next. Applying this treatment to human studies for snoring and OSA applications is the ultimate goal.

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle contrast followed with the next instrument, termed speckle contrast diffuse correlation tomography (scDCT). In scDCT, an optical switch sequenced coherent near-infrared light into contact-based source fibers around the sample surface. A fully noncontact reflectance mode device finalized improvements by combining noncontact scDCT (nc_scDCT) and diffuse fluorescence tomography (DFT) techniques. In the combined device, a galvo-mirror directed polarized light to the sample surface. Filters and a cross polarizer in stackable tubes promoted extracting flow indices, absorption coefficients, and fluorescence concentrations (indocyanine green, ICG). The scDCT instrumentation was validated through detection of a cubical solid tissue-like phantom heterogeneity beneath a liquid phantom (background) surface where recovery of its center and dimensions agreed with the known values. The combined nc_scDCT/DFT identified both a cubical solid phantom and a tube of stepwise varying ICG concentration (absorption and fluorescence contrast). The tube imaged by nc_scDCT/DFT exhibited expected trends in absorption and fluorescence. The tube shape, orientation, and localization were recovered in general agreement with actuality. The flow heterogeneity localization was successfully extracted and its average relative flow values in agreement with previous studies. Increasing ICG concentrations induced notable disturbances in the tube region (≥ 0.25 μM/1 μM for 785 nm/830 nm) suggesting the graduating absorption (320% increase at 785 nm) introduced errors. We observe that 830 nm is lower in the ICG absorption spectrum and the correspondingly measured flow encountered less influence than 785 nm. From these results we anticipate the best practice in future studies to be utilization of a laser source with wavelength in a low region of the ICG absorption spectrum (e.g., 830 nm) or to only monitor flow prior to ICG injection or post-clearance. In addition, ncDCT was initially tested in a mouse tumor model to examine tumor size and averaged flow changes over a four-day interval. The next steps in forwarding the combined device development include the straightforward automation of data acquisition and filter rotation and applying it to in vivo tumor studies. These animal/clinical models may seek information such as simultaneous detection of tumor flow, fluorescence, and absorption contrasts or analyzing the relationship between variably sized fluorescently tagged nanoparticles and their tumor deposition relationship to flow distributions.