The purpose of this thesis was to demonstrate device functionality of 3-D paper-based, multiplex platforms, µPADs, without the use of coupling agents between layers. Previously, these platforms were fabricated with double-sided tape and cellulose powder to try to augment proper fluid routing, but difficulties with this method occurred. An acrylic housing unit with strategically placed pressure tabs was designed to aid horizontal and vertical fluid routing through the platform, thus eliminating the inconsistencies associated with coupling agents. Channel characterization studies, a COMSOLTM simulation, and development time studies were performed to aid device design and demonstrate device functionality. The implementation of this µPAD platform as a diagnostic instrument was validated via lateral flow immunoassays utilizing both biotinylated antibodies and biotinylated aptamers as capture reagents. Successful detection of the target analyte, IgE, as well as successful fluid routing through multiple layers of membrane was demonstrated by immunoassays performed on 3-D, multiplex platforms. Another important result determined the aptamers’ ability to detect IgE to be statistically the same as the antibodies’ ability; thus confirming aptamers as viable capture reagent alternatives to antibodies in lateral flow assays. Overall, this research project was performed to develop and validate via experiment a prototype paper-based microfluidic diagnostic device, µPAD, with the capability to detect multiple biomarkers on one platform.

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.

The vestibular system senses head motion and facilitates gaze stabilization, allowing for clear vision during movement. The vestibulo-ocular reflex (VOR) causes the eyes to move opposite head motion, thus maintaining focus on a target. Consequently, uncompensated loss of vestibular function leads to reduced VOR function resulting in dizziness, nausea, and visual disturbance. Different testing methods have been developed to measure VOR loss. These tests generally require bulky, expensive equipment, and must be performed by a trained examiner. A newly developed digital form of the dynamic visual acuity (DVA) test requires less equipment, is cost-effective, and may be performed at home making it more accessible. The purpose of this study was to determine the validity and test-retest reliability of the digital DVA test and provide normative data for healthy adults. Fifteen adults – 10 female and 5 male (mean age = 22.0 ± 3.1, range: 19-31 years) – completed the study. Exclusion criteria included age older than 49 years, history of vestibular or neurological disorders, and history of significant head injury. Subjects were screened for normal vestibular function using video head impulse testing. The study consisted of two visits, 3-15 days apart. Participants underwent DVA testing with both the validated NeuroCom (InVision software) system and newly developed digital DVA during the initial visit and the digital DVA during the second visit. The digital DVA system consists of a laptop computer paired with a head/eye tracker (Tobii Eye Tracker 5) and Health in Motion software (Blue Marble Health Company). Outcome measures of interest were the difference between static and dynamic visual acuity measured in LogMAR (DVA loss) for rightward and leftward head movement. Pearson Product-Moment bivariate correlations were used to determine validity of the digital DVA outcomes compared to NeuroCom outcomes. Intraclass correlation coefficients (ICCs) were calculated to determine test-retest reliability of the digital DVA. Pearson correlation coefficients for validity were r = 0.025 and r = -0.015 for left and right DVA loss, respectively. ICCs for test-retest reliability were r = 0.366 and r = 0.313 for left and right DVA loss, respectively. Mean values across both sessions for left and right DVA loss measured by digital DVA were 0.26 ± 0.13 and 0.26 ± 0.11, respectively. Correlations between the digital DVA and standard computerized DVA were poor indicating the need for further development of the current digital system/software. Test-retest reliability for the digital DVA system in its current state was also poor. Tobii sensor used in the software is limited by a 200 ms delay in reporting head motion to the software. Future development of a digital DVA may need to consider other sensors. The current digital DVA will not replace the computerized system; however, it may provide important information for clinicians who do not have access to computerized DVA.

Every gas molecule has a unique absorption spectrum that can be captured using optical spectroscopy to identify an unknown sample's composition. Frequency combs systems can provide an extremely broad mid-infrared spectrum that is very useful for molecular detection. A degenerate optical parametric oscillator (OPO) was built to generate the down-converted and shifted frequency comb spectrum. This system utilizes an ultra-short pulse 1.56µm pump laser and a never before used orientation patterned gallium-phosphide crystal. Periodically polled lithium niobate (PPLN), Gallium Arsenide (GaAs) and Gallium Phosphide are all crystals used to accomplish this task. GaP, in comparison to PPLN, has (i) a larger nonlinear coefficient, (ii) much deeper infrared transparency, and (iii) smaller group dispersion – to allow for achieving broad spectral coverage. GaP also has a larger band gap than GaAs; therefore it can still be pumped with a standard telecom C-band laser. An octave-wide spanning frequency comb system was achieved and the characterization of the system is presented. This system is specifically designed to be compact and portable for initial experimental testing in the applications of medical breath analysis and combustion gas investigation.

<p><strong>BACKGROUND</strong>.<strong> </strong>Classically, radiography (x-ray) has been used to visualize the destructive effects of uncontrolled rheumatoid arthritis (RA) on articular bones. Both x-ray and magnetic resonance imaging (MRI) may be used to visualize erosive disease. The multi-slice and multi-planar characteristics of MRI provide greater detail per anatomy imaged than x-ray.</p> <p><strong>OBJECTIVE</strong>. The objective of this dissertation was to compare the relative merits of x-ray and MRI erosion detection.</p> <p><strong>METHODS</strong>. In Chapters 1 through 3, RA, its clinical management, and the role of diagnostic imaging were introduced. In Chapter 4, the overall objective was first investigated by evaluating the current state of knowledge using a systematic review. In Chapter 5, inter-rater reliability across four participating radiologists was investigated. In Chapter 6, reliability-adjusted evaluations were used to directly compare paired x-ray and MR images.</p> <p><strong>RESULTS</strong>. The systematic review indicated that x-ray has low sensitivity and high specificity for MRI erosions. The associations were dependent on RA symptom duration. The findings from the prospective studies conducted were consistent with the literature. In a patient-centred analysis, the proportion of patients with erosive disease detected on either modality was dependent on the anatomy compared. Despite similar proportions of patients with erosive disease detected in comparable diagnostic imaging sittings, the proportions were comprised of markedly different patients.</p> <p><strong>CONCLUSIONS</strong>. The literature comparing x-ray and MRI erosion detection was systematically reviewed. The dependence of the relative diagnostic test accuracy on symptom duration was highlighted. At the patient level of analysis, the greater number of anatomical sites examined on x-ray overcomes the superiority of MRI to detect erosions at the unit of measurement. The two modalities are complementary insofar that they detect erosive disease in distinct patients. Further investigation into the merit of imaging varied anatomy on MR and optimally accounting for inter-rater reliability in such comparisons is warranted.</p> / Doctor of Philosophy (PhD)

This research presents a framework for enhancing and analyzing time-sequenced mammographic images for detection of cancerous tissue, specifically designed to assist radiologists and physicians with the detection of breast cancer. By using computer aided diagnosis (CAD) systems as a tool to help in the detection of breast cancer in computed tomography (CT) mammography images, previous CT mammography images will enhance the interpretation of the next series of images. The first stage of this dissertation applies image subtraction to images from the same patient over time. Image types are defined as temporal subtraction, dual-energy subtraction, and Digital Database for Screening Mammography (DDSM). Image enhancement begins by applying image registration and subtraction using Matlab 2012a registration for temporal images and dual-energy subtraction for dual-energy images. DDSM images require no registration or subtraction as they are used for baseline analysis. The image data are from three different sources and all images had been annotated by radiologists for each image type using an image mask to identify malignant and benign. The second stage involved the examination of four different thresholding techniques. The amplitude thresholding method manipulates objects and backgrounds in such a way that object and background pixels have grey levels grouped into two dominant and different modes. In these cases, it was possible to extract the objects from the background using a threshold that separates the modes. The local thresholding introduced posed no restrictions on region shape or size, because it maximized edge features by thresholding local regions separately. The overall histogram analysis showed minima and maxima of the image and provided four feature types--mean, variance, skewness, and kurtosis. K-means clustering provided sequential splitting, initially performing dynamic splits. These dynamic splits were then further split into smaller, more variant regions until the regions of interest were isolated. Regional-growing methods used recursive splitting to partition the image top-down by using the average brightness of a region. Each thresholding method was applied to each of the three image types. In the final stage, the training set and test set were derived by applying the four thresholding methods on each of the three image types. This was accomplished by running Matlab 2012a grey-level, co-occurrence matrix (GLCM) and utilizing 21 target feature types, which were obtained from the Matlab function texture features. An additional four feature types were obtained from the state of the histogram-based features types. These 25 feature types were applied to each of the two classifications malignant and benign. WEKA 3.6.10 was used along with classifier J48 and cross-validation 10 fold to find the precision, recall, and f-measure values. Best results were obtained from these two combinations: temporal subtraction with amplitude thresholding, and temporal subtraction with regional-growing thresholding. To summarize, the researcher's contribution was to assess the effectiveness of various thresholding methods in the context of a three-stage approach, to help radiologists find cancerous tissue lesions in CT and MRI mammography images.

When face-to-face physical medical exams are not possible, virtual physical exams, in the form of a pictorial medical exam/history, can be substituted, and telemedicine can be the means to deliver these virtual exams. The goal of this work was to determine if presence in the form of a visual and/or pictorial medical history can be of benefit to clinicians in the diagnosis of medical conditions of individuals with developmental disabilities (DDs) and/or intellectual disabilities (IDs), in particular those who cannot, because of their cognitive and/or physical disabilities, verbally relate their illness to a clinician. Virtual exams can also be useful in cases where clinicians may need additional advice from fellow experts, especially if those experts are not physically present. A web-based telemedicine application used for treating persons with DD/IDs was developed. This application includes a visual medical history component incorporated into an electronic medical records application. The purpose is to allow the clinician to use an environment that integrates a written and visual representation of a patient’s medical history and physical findings to aid the clinician in determining a medical diagnosis. Twenty-two clinicians and five direct service aids of a New York State Developmental Disabilities Services Office facility, who deliver healthcare to DD/ID patients on a daily basis, accessed the telemedicine application instead of their traditional hardcopy/paper medical history when examining patients. A comprehensive survey was distributed to the clinicians to determine the effectiveness of the application as well as help answer the primary questions proposed by this research. The results of this study showed that presence in the form of a video medical history is preferred by clinicians rather than having just a written medical history of the patient. Clinicians felt the visual medical history component of the telemedicine application was useful and informative for delivering healthcare to individuals with DD/ID and enabled them in diagnosing a patient as well as lessened the need to transfer patients to the emergency room, resulting in a significant cost savings.

Diabetes is the seventh leading cause of death in the United States. With the population rapidly aging, it is expected that 1 out of 3 Americans will have diabetes by 2050. Mobile devices and mobile applications have the potential to contribute to diabetes self-care by allowing users to manage their diabetes by keeping track of their blood glucose levels. Usability is important for systems that help people self-manage conditions such as diabetes. Age and diabetes-related cognitive decline might intensify the impact of usability issues for the users who need these mobile applications the most. As highlighted by usability researchers, the context of use (i.e. environment, user, task, and technology) has a significant impact on usability. The environment (lighting, temperature, audio and visual distractions, etc.) is of special interest to the mobile usability arena since in the case of mobile devices, is always changing. This dissertation aims to support the claim that context and more specifically environmental distraction such as semantic auditory distractions impact the usability of mobile applications. In doing so, it attempts to answer the following research questions: 1) Does semantic auditory distractions reduce the effectiveness of a blood glucose tracking mobile application? 2) Does semantic auditory distractions reduce the efficiency of a blood glucose tracking mobile application? 3) Does semantic auditory distractions reduce the user satisfaction of a blood glucose tracking mobile application? To answer the study research questions, a true experimental design was performed involving 30 adults with type 2 diabetes. Participants were paired based on their age and experience with smartphones and randomly assigned to the control (no semantic auditory distractions) or experimental (semantic auditory distractions) group. Research questions were tested using the general linear model. The results of this study confirmed that semantic auditory distractions have a significant effect on efficiency and effectiveness, and hence they need to be taken into account when evaluating mobile usability. This study also showed that semantic auditory distractions have no significant effect on user satisfaction. This dissertation enhances the current knowledge about the impact of semantic auditory distractions on the usability of mobile applications within the diabetic senior population.

The primary purpose of this investigation was to explore the effects of varying degrees of vocal tract semi-occlusion in Vocal Function Exercises (VFEs) on attainment of pre- established maximum phonation time (MPT) goals in individuals between the ages of 18 and 45 with normal voice. Individuals were randomized into three experimental groups: the traditional VFE with a semi-occluded vocal tract (SOVT), modified /o/ with partial occlusion, and modified /a/ without significant occlusion. For six weeks, the participants completed the four exercises two times each, twice daily on corresponding vocal tract postures assigned by group. Results indicated significant change in percent of MPT goal attained for the traditional VFE group. Neither modified vocal tract group resulted in significant change. Decreased occlusion appears insufficient in producing substantial change in voice production despite increased compliance compared to the traditional VFE group.

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers. Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such as infections and certain medications, consequently leading to false positive diagnoses and unnecessary concern and over treatment with dire outcomes for the patient. Even worse, are the chances of false negative diagnoses, which result in prostate cancer not being diagnosed until its later stages. Therefore, although the use of the PSA level has had its uses in the clinic, it has failed to sufficiently bridge the gap or to distinguish indolent from aggressive disease. It has long been suggested in the literature that microRNAs are drastically altered throughout the course of cancer progression. Here, RNA sequencing was used to identify changes in miR expression profiles diagnostic for prostate cancer patients compared to non-patient controls. The RNA sequencing results were also used to identify normalization miRs to be used as endogenous controls. Confirmatory qRT-PCR was then used to corroborate these results for the top seven dysregulated miRs found from the RNA sequencing data. Data analysis of the Area Under the Curve (AUC) of the Receiver Operating Curves (ROC) of the selected miRs exhibited a better correlation with prostate cancer (AUC Range= 0.819- 0.950) than PSA (AUC of PSA=0.667). In summary, a panel of seven miRs are proposed, many of which have prostate specific targets, which would represent a significant improvement over current testing methods.