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.

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis was improved by simultaneously extracting multiple parameters from one single autocorrelation function curve measured by DCS. Patients were classified into two groups based on clinical outcomes: a complete response (CR) group and an incomplete response (IR) group with remote metastasis and/or local recurrence within one year. Interestingly, we found human papilloma virus (HPV-16) status largely affected tumor homodynamic responses to therapy. Significant differences in tumor blood flow index (BFI) and reduced scattering coefficient (μs’) between the IR and CR groups were observed in HPV-16 negative patients at Week 3. Significant differences in oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) between the two groups were found in HPV-16 positive patients at Week 1 and Week 3, respectively. Receiver operating characteristic curves were constructed and results indicated high sensitivities and specificities of these hemodynamic parameters for early (within the first three weeks of the treatment) prediction of one-year treatment outcomes. Measurement of tumor hemodynamics may serve as a predictive tool allowing treatment selection based on biologic tumor characteristics. Ultimately, reduction of side effects in patients not benefiting from radiation treatment may be feasible.

In immersive audio environments with distributed microphones, Independent Component Analysis (ICA) can be applied to uncover signals from a mixture of other signals and noise, such as in a cocktail party recording. ICA algorithms have been developed for instantaneous source mixtures and convolutional source mixtures. While ICA for instantaneous mixtures works when no delays exist between the signals in each mixture, distributed microphone recordings typically result various delays of the signals over the recorded channels. The convolutive ICA algorithm should account for delays; however, it requires many parameters to be set and often has stability issues. This thesis introduces the Channel Aligned FastICA (CAICA), which requires knowledge of the source distance to each microphone, but does not require knowledge of noise sources. Furthermore, the CAICA is combined with Time Frequency Masking (TFM), yielding even better SOI extraction even in low SNR environments. Simulations were conducted for ranking experiments tested the performance of three algorithms: Weighted Beamforming (WB), CAICA, CAICA with TFM. The Closest Microphone (CM) recording is used as a reference for all three. Statistical analyses on the results demonstrated superior performance for the CAICA with TFM. The algorithms were applied to experimental recordings to support the conclusions of the simulations. These techniques can be deployed in mobile platforms, used in surveillance for capturing human speech and potentially adapted to biomedical fields.

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles' toxicity, as well.

This research used a focused ion beam in order to fabricate record small nano-magnetic structures, investigate the properties of magnetic materials in the rarely studied range of nanometer size, and exploit their extraordinary characteristics in medicine and nano-electronics. This study consists of two parts: (i) Fabrication and study of record small magnetic tunnel junctions (ii) Introduction of a novel method for detection of magnetoelectric nanoparticles (MENs) in the tissue. A key challenge in further scaling of CMOS devices is being able to perform non-volatile logic with near zero power consumption. Sub-10-nm nanomagnetic spin transfer torque (STT) magnetic tunneling junctions (MTJs) have the potential for a universal memory that can address this key challenge. The main problem is to decrease the switching current density. This research studied these structures in sub-10-nm size range. In this range, spin related excitations consume considerably smaller amounts of energy as compared to the larger scale. This research concluded that as predicted a decrease in switching current superior to that of the linear scaling will happen in this size range. Magneto-electric nanoparticles (MENs) can be used to directly couple intrinsic electric-field-driven processes with external magnetic fields for controlling neural activity deep in the brain. These particles have been proven to be capable of inducing deep brain stimulation non-invasively. Furthermore, these magneto-electric nano-particles can be used for targeted drug delivery and are contenders to replace conventional chemotherapy. The circulatory system can deliver a drug to almost every cell in the body; however, delivering the drug specifically into the tumor cell and then releasing it on demand remains a formidable task. Nanomedicine can accomplish this, but ensuring that the drug is released at an appropriate rate once at the target site is an important task. In order to have a complete understanding of the behavior of these MENs when injected into the body, a comprehensive bio-distribution study was performed. This study introduced a novel spectroscopy method for tracing the nanoparticles in the bloodstream. This study investigated the post injection distribution of the MENs in vital organs throughout a period of two months.

Point-of-care testing (POCT) is defined as medical testing at or near the site of patient care and has become a critical component of the diagnostic industry. POCT has many advantages over tests in centralized laboratories including small reagent volumes, small size, rapid turnaround time, cost-effectiveness, low power consumption and functional integration of multiple devices. Paper-based POCT sensors are a new alternative technology for fabricating simple, low-cost, portable and disposable analytical devices for clinical diagnosis. The focus of this dissertation was to develop simple, rapid and low cost paper-based POCT sensors with high sensitivity and portability for disease biomarker detection. Lateral flow strips (LFS) were used as the basic platform as it provides several key advantages such as simplicity, fast response time, on site and cost-effectiveness, and it can be used to detect specific substances including small molecules, large proteins and even whole pathogens, in a sample by immunological reactions. Earlier designs of paper strips lacked the quantitative information of the analyte concentration and could only provide single analyte detection at a time. In this study, a series of modifications were made to upgrade the platform to compensate for these limitations. First, we developed a gold nanoparticle based LFS for qualitative colorimetrical detection of bladder cancer related biomarkers in standard solutions and in urine samples. Second, by incorporating an image processing program “ImageJ”, a semi-quantitative LFS platform was established. The capability of the strip was evaluated by testing a small DNA oxidative damage biomarker in urine and cell culture models. Third, we combined the electrochemical method and colorimetrical method for quantitative biomarker detection. Finally, we integrated a commercialized blood glucose meter to quantitatively detection of two non-glucose biomarkers by converting their signals to that of glucose. The upgraded sensor could provide a noninvasive, rapid, visual, quantitative and convenient detection platform for various disease biomarkers. In addition, this platform does not require expensive equipments or trained personnel, deeming it suitable for use as a simple, economical and portable field kit for on-site biomarker monitoring in a variety of clinical settings.

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.

Personal computers and portable electronics continue to rapidly advance and integrate into our lives as tools that facilitate efficient communication and interaction with the outside world. Now with a multitude of different devices available, personal computers are accessible to a wider audience than ever before. To continue to expand and reach new users, novel user interface technologies have been developed, such as touch input and gyroscopic motion, in which enhanced control fidelity can be achieved. For users with limited-to-no use of their hands, or for those who seek additional means to intuitively use and command a computer, novel sensory systems can be employed that interpret the natural electric signals produced by the human body as command inputs. One of these novel sensor systems is the myoelectric detection circuit, which can measure electromyographic (EMG) signals produced by contracting muscles through specialized electrodes, and convert the signals into a usable form through an analog circuit. With the goal of making a general-purpose myoelectric detection circuit platform for computer interface applications, several electrical circuit designs were iterated using OrCAD software, manufactured using PCB fabrication techniques, and tested with electrical measurement equipment and in a computer simulation. The analog circuit design culminated in a 1.35” x 0.8” manufactured analog myoelectric detection circuit unit that successfully converts a measured EMG input signal from surface skin electrodes to a clean and usable 0-5 V DC output that seamlessly interfaces with an Arduino Leonardo microcontroller for further signal processing and logic operations. Multiple input channels were combined with a microcontroller to create an EMG interface device that was used to interface with a PC, where simulated mouse cursor movement was controlled through the voluntary EMG signals provided by a user. Functional testing of the interface device was performed, which showed a long battery life of 44.6 hours, and effectiveness in using a PC to type with an on-screen keyboard.

This thesis designed and fabricated various devices that were interfaced to an IC for an active contact lens that notifies the user of an event by detection of an external wireless signal. The contact lens consisted of an embedded antenna providing communication with a 2.4GHz system, as well as inductive charging at an operating frequency of 13.56 MHz. The lens utilized a CBC005 5µAh thin film battery by Cymbet and a manufactured graphene super capacitor as a power source. The custom integrated circuit (IC) was designed using the On Semiconductor CMOS C5 0.6 µm process to manage the battery and drive the display. A transparent, flexible, single cell display was developed utilizing electrochromic ink to indicate to the user of an event. Assembly of the components, encapsulation, and molding were implemented to create the final product. The material properties of the chosen substrate were analyzed for their clearness, flexibility, and biocompatibility to determine its suitability as a contact lens material. Finally, the two different fabrication techniques (microfabrication and screen printing) that were employed to make the devices are compared to determine the favorable process for each part of the system.

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.