The current gold standard treatment for bone defects is autologous cancellous bone graft, which involves increased surgery time and donor site morbidity, and limited supply of bone and cells for regeneration. Bioreactors may aid in the generation of mechanically conditioned bone grafts with more cells compared to traditional grafts. However, the specific parameters of fluid flow and mechanical loading which contribute to osteogenesis and cell viability in bioreactors are not fully characterized. Here, a perfusion-compression bioreactor system was developed to study osteogenesis in porcine trabecular bone explants. Loading accuracy was over 88% across six bioreactors at a 0.1 s-1 strain rate and 20 N target force, akin to running. A flow rate of 0.2 mL/min appeared to be more favorable for cell viability than 1 mL/min. Overall, this work offers a foundation for future efforts to enhance cell viability and osteogenesis in bone explants.

<p>Minimally invasive operations have gained popularity over open surgical procedures in the recent years. These procedures, require the surgeon to perform highly specialized tasks including manipulation of tools through small incisions on the surface of the skin while looking at the images that are displayed on a screen. Therefore, effective training is required for the surgeons prior to performing such procedures on patients.</p> <p>In this thesis I explored a novel idea for creating a training system for arthroscopic surgery. Previously obtained CT images of a patient model and the surgical tools are manipulated to create a library of fluoroscopy images. The surgical tools are tracked (a mechanical tracker and an electromagnetic tracker used in each iterations) in order to generate a spacial relationship between the patient model and the surgical tools. The position and orientation information from the tracking system is translated into the image coordinate frame. These homologous points in the two images (of surgical tools and the patient model), are used to co-register and overlay the two images and create a virtual fluoroscopy image.</p> <p>The output image and the system performance was found to be very good and quite similar to that of a fluoroscopy system. The registration accuracy was evaluated using Root Mean Square Target Registration Error (RMS TRE). The RMS TRE for the system setup with the mechanical tracker was evaluated at 2:0 mm, 2:1 mm, and 2:5 mm, for 4, 5, and 6 control points, respectively. In the system setup with the electromagnetic tracking system the RMS TRE was evaluated at 7:6 mm, 12:4 mm, and 11:3 mm, for 5, 7, and 9 control points, respectively. The acceptable range of error for arthroscopy procedures has been proposed to be 1-2 mm.</p> <p>It was concluded that by using a tracking system, which is not prone to interference and allows for a wide range of motion this system can be completed to the point of manufacturing and use in training new surgeons.</p> / Master of Applied Science (MASc)

Intuitive prosthetic control is limited by the inability to easily convey intention and perceive physical requirements of the task. Rather than providing haptic feedback and allowing users to consciously control every component of manipulation, relegating some aspects of control to the device may simplify operation. This study focuses on the development and testing of a control scheme able to identify object stiffness and regulate impedance. The system includes an algorithm to detect the apparent stiffness of an object, a proportional nonlinear EMG control algorithm for interpreting a user’s desired grasp aperture, and an antagonistically acting impedance controller. Performance of a testbed prosthetic simulation used to controllably extrude pastes of different properties from a compliant tube was compared to that of the non-dominant human hand. The paste volume extrusion error and response time to perform the task were recorded for comparison. Statistical analysis using (GEE) and (TOST) suggests the prosthetic controller and human hand performed similarly along these metrics. Performance differences in the trials were more strongly correlated to tube type and repetition block. The results suggest that the developed controller allows users to perform a controlled squeezing task at a level comparable to the human hand with minimal training. It also suggests that a priori stiffness estimation acquired through quick palpations may be sufficient for effective control during simple manipulation. The lack of a learning curve suggests that the development of systems that automatically control aspects of mechanical interaction may offer users more advanced control capabilities with low cognitive load.

Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. During the first 3 minutes of tilt, systolic BP decreased in D2 while increased in AB. Parasympathetic control of heart rate, baroreflex sensitivity, and baroreflex effectiveness and sympathetic control of heart rate and vasomotion were reduced in D2, compared with AB. Baroreflex effectiveness index was identified as the most sensitive index to discriminate diabetic AN. Four-dimensional multiscale modeling of ECG indexes of diabetic autonomic neuropathy: QT interval prolongation which predicts long-term mortality in diabetics with AN, is well known. The mechanism of QT interval prolongation is still unknown, but correlation of regional sympathetic denervation of the heart (revealed by cardiac imaging) with QT interval in 12-lead ECG has been proposed. The goal of this study is to 1) reproduce QT interval prolongation seen in diabetics, and 2) develop a computer model to link QT interval prolongation to regional cardiac sympathetic denervation at the cellular level. From the 12-lead ECG acquired in the study above, heart rate-corrected QT interval (QTc) was computed and a reduced ionic whole heart mathematical model was constructed. Twelve-lead ECG was produced as a forward solution from an equivalent cardiac source. Different patterns of regional denervation in cardiac images of diabetic patients guided the simulation of pathological changes. Minimum QTc interval of lateral leads tended to be longer in D2 than in AB. Prolonging action potential duration in the basal septal region in the model produced ECG and QT interval similar to that of D2 subjects, suggesting sympathetic denervation in this region in patients with definite neuropathy.

Today, advances in wireless sensor networks are making it possible to capture large amounts of information about a person and their interaction within their home environment. However, what is missing is how to ensure the security of the collected data and its use to alter human behavior for positive benefit. In this research, exploration was conducted involving the "infrastructure" and "intelligence" aspects of a wireless sensor network through a Behavior Modification Sensor System. First was to understand how a secure wireless sensor network could be established through the symmetric distribution of keys (the securing of the infrastructure), and it involves the mathematical analysis of a novel key pre-distribution scheme. Second explores via field testing the "intelligence" level of the system. This was meant to support the generation of persuasive messages built from the integration of a person's physiological and living pattern data in persuading physical activity behavior change associated with daily walking steps. This system was used by an elderly female in a three-month study. Findings regarding the "infrastructure" or the novel key pre-distribution scheme in comparison to three popular key distribution methods indicates that it offers greater network resiliency to security threats (i.e., 1/2^32 times lower), better memory utilization (i.e., 53.9% less), but higher energy consumption (i.e., 2% higher) than its comparison group. Findings from the "intelligence" level of the research posit that using a person's physiological and living pattern data may allow for more "information rich" and stronger persuasive messages. Findings indicate that the study participant was able to change and improve her average daily walking steps by 61% over a pre-treatment period. As the study participant increased her physical activity, changes in her living pattern were also observed (e.g., time spent watching television decreased while time spent engaged in walking increased by an average of 15 minutes per day). Reinforcement of these findings were noted between a pre and post-study survey that indicated the study participant moved from a contemplation stage of change where physical activity engagement was intended but not acted upon to an action stage of change where physical activity engagement dominated the new behavior.

For this project, the design, implementation, characterization, calibration and possible applications of a multiple transducer stethoscope apparatus were investigated. The multi-transducer sensor array design consists of five standard stethoscope diaphragms mounted to a rigid frame for a-priori knowledge of their relative spatial locations in the x-y plane, with compliant z-direction positioning to ensure good contact and pressure against the subject’s skin for reliable acoustic coupling. When this apparatus is properly placed on the body, it can digitally capture the same important body sounds investigated with standard acoustic stethoscopes; especially heart sounds. Acoustic signal inputs from each diaphragm are converted to electrical signals through microphone pickups installed in the stethoscope connective tubing; and are subsequently sampled and digitized for analysis. With this system, we are able to simultaneously interrogate internal body sounds at a sampling rate of 2 KHz, as most heart sounds of interest occur below 200 Hz. This system was characterized and calibrated by chirp and impulse signal tests. After calibrating the system, a variety of methods for combining the individual sensor channel data to improve the detectability of different signals of interest were explored using variable-delay beam forming. S1 and S2 heart sound recognition with optimized beam forming delays and inter-symbol noise elimination were investigated for improved discernment of the S1 or S2 heart sounds by a user. Also, stereophonic presentation of heart sounds was also produced to allow future investigation of its potential clinical diagnostic efficacy.

<p>A microfluidic device capable of drug delivery to multiple wells in a concentration gradient was designed for automated high content and high throughput screening. The design was proposed to utilize a nanoporous polycarbonate membrane to spatially and temporally control drug dosage from the microchannels below to the wells above. Microchannels were to hold to the drugs or reagents, while wells were to culture cells. An array of 16 wells was to fit in the equivalent area of a single well of a 96 well plate. Two simpler devices were created to validate electrokinetic drug delivery to a single well and to characterize cell proliferation and viability in micro-wells. The first device tested drug delivery to a single well with methylene blue dye at applied voltages of 100V, 125V, and 150V. It was validated that the dosage of dye could be controlled by increasing the voltage and by increasing the duration the voltage was applied. The second devices were a series of 9-well arrays, each testing a different diameter (1.2 mm – 0.35 mm). These devices were cultured with MCF-7 breast cancer cells over 5 days. At the end of the 5 day study, all diameters except for 0.5 mm and 0.35 mm measured a cell viability of 99% and exhibited cell growth patterns similar to coverslip glass controls. The proposed integrated cell culture and drug delivery device could have application towards early stage drug discovery and could have compatibility with lab equipment originally designed for well plates.</p> / Master of Applied Science (MASc)

This thesis proposes an algorithm that determine the geometry of 3D-printed, custom-designed spring element bands made of thermoplastic elastomer (TPE) for use in a wearable orthotic device to aid in the physical therapy of a human hand exhibiting spasticity after stroke. Each finger of the hand is modeled as a mechanical system consisting of a triple-rod pendulum with nonlinear stiffness at each joint and forces applied at the attachment point of each flexor muscle. The system is assumed quasi-static, which leads to a torque balance between the flexor tendons in the hand, joint stiffness and the design force applied to the fingertip by the 3D-printed spring element. To better understand material properties of the spring element’s material, several tests are performed on TPE specimens printed with different infill geometries, including tensile tests and cyclic loading tests. The data and stress-strain curves for each geometry type are presented, which yield a nonlinear relationship between stress and strain as well as apparent hysteresis. Polynomial curves are used to fit the data, which allows for the band geometry to be designed. A hypothetical hand is presented along with how input measurements might be taken for the algorithm. The inputs are entered into the algorithm, and the geometry of the bands for each finger are generated. Results are discussed, and future work is noted, providing a means for the design of a customized orthotic device.

This thesis presents a new mechanical design for an exoskeleton actuator to power the sagittal plane motion in the human hip. The device uses a DC motor to drive a Scotch yoke mechanism and series elasticity to take advantage of the cyclic nature of human gait and to reduce the maximum power and control requirements of the exoskeleton. The Scotch yoke actuator creates a position-dependent transmission that varies between 4:1 and infinity, with the peak transmission ratio aligned to the peak torque periods of the human gait cycle. Simulation results show that both the peak and average motor torque can be reduced using this mechanism, potentially allowing a less powerful motor to be used. Furthermore, the motor never needs to reverse direction even when the hip joint does. Preliminary testing shows the exoskeleton can provide an assistive torque and is capable of accurate position tracking at speeds covering the range of human walking. This thesis provides a detailed analysis of how the dynamic nature of human walking can be leveraged, how the hip actuator was designed, and shows how the exoskeleton performed during preliminary human trials.

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the chamber design and the control system. These concepts were compared against developed engineering specs and were evaluated amongst the team and sponsor. From there, a detailed CAD model was developed and utilized to design the structure and was used as a guide for manufacturing. The control system was prototyped on breadboards via Arduino. This breadboard testing served as the map to solder perf boards, which are utilized as the final structure for the control system. Once all parts were sourced, machined, and assembled for the final chamber and the control system, these subassemblies were integrated together with a regulated gas system via various tubing. The integrated final design underwent a variety of testing to validate the incubator design and control system. Testing was performed throughout the course of this project: material testing, gas leak testing, cell test, temperature control test, and gas control system optimization; however, the most important of these tests were those relating to the environmental control of the incubator. These tests confirmed whether the incubator design was functional as a practical incubator. Testing confirmed that O2 and temperature control maintained in spec over a short and long period of time while maintaining a humid environment. CO2 control optimization had more complications than the O2 hypoxia system. During testing CO2 concentration would typically overshoot the set point, likely due to a lack of precise control over the gas flow. CO2 variability was reduced due to optimization in the code, but not fully mitigated. Future iterations of this chamber could improve upon the CO2 control and streamline the user interface.