Browsing by Author "Murari, Kartikeya"
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Item Open Access 3D printing in Clinical Diagnostics: A Versatile Tool to Develop Testing Devices for the Diagnosis of Infectious Diseases(2023-01-05) Aburashed, Raied; Sanati Nezhad, Amir; Lewis, Ian; Kim, Seonghwan; Murari, Kartikeya3D printing (3DP) has recently emerged as an advanced manufacturing technology in the pharmaceutical and biomedical industries. 3DP has virtually become a synonym for rapid prototyping. The ease of use and low cost of in-house 3D printing has also revolutionized product development, and many manufacturers of medical tools have adopted the technology to produce brand-new medical devices and surgical instruments. 3DP allows for a fast feedback loop which accelerates design development; designers and manufacturers can rely on the use of early 3D printed parts to support clinical trials or early commercialization while the final design is still being optimized. This relationship was crucial in support of enhanced health care and general emergency response, as shown during the COVID-19 pandemic. A few examples where 3DP technologies were used to validate product efficacy include 3DP nasal pharyngeal swabs, multiplexing of bi-level positive airway pressure (BiPAP) machines to support multiple patients, patient-specific dental moulding, and antigen testing kits for COVID-19. In this dissertation, I show the versatility of 3D printing within the infectious disease workflow. Firstly, I demonstrate the use of 3D printing in patient sample collection through the development of a novel 3D manufacturing and efficacy validation for nasal pharyngeal (NP) swabs. With the aim to develop a swab (a) 3D printed with complex tip structures for enhanced sample collection efficacy, eliminating the need to apply flocks at the tips (b) scalability with a network of 3D printing capacity in biomedical devices and biocompatible material applications, and (c) ability to rapidly iterate prototypes quickly and effectively without incurring costs of machining moulds for injection moulding. In the following chapter, I discuss the importance and use of rapid manufacturing techniques to develop diagnostic assay kits for various diseases; predominantly in the development of point-of-care (POC) devices through the combination of microfluidic and microelectromechanical systems (MEMS). 3DP techniques can be utilized to develop various fluidic systems to streamline laboratory testing methodologies. I explore the development of a centrifugal microfluidic platform and the manufacturability of various centrifugal fluidic systems within the limitation of 3DP. This work aims to provide the building blocks of the 3D printing of various centrifugal microfluidic modules and establishes a proof-of-concept AST platform for bloodstream infections by sensing and monitoring the growth and antibiotic susceptibility of E. coli. Finally, I show the utility of 3DP in clinical diagnostics through the rapid development of a custom 96-well plate platform; microbial containment device (MCD) and software package FUGU-MS – Filtering Utility for Grouping untargeted mass spectrometry data and open-source software tool to compliment the metabolic data acquired via the MCD. The 3D printed MCD that allows water-soluble metabolites to diffuse from a microbial culture well into a bacteria-free well through a semi-permeable membrane, which allows for streamline sample processing for clinical diagnostics of bloodstream infections. The MCD validated through the analysis of the metabolic flux to identify different strains of bacteria, including Escherichia coli, Klebsiella pneumonia, Enterococcus faecalis and Staphylococcus aureus following a 4-hour incubation period of various bloodstream and urinary tract pathogens and direct sampling onto a Q Exactive HF Hybrid Quadrupole-Orbitrap Mass Spectrometer.Item Open Access A Single Fiber System for Monitoring Tissue Oxygen Saturation(2015-09-28) Yu, Linhui; Murari, KartikeyaOxygen saturation is an important biological marker in tissue and is often quantified using optical imaging of intrinsic signals. However, due to the scattering property of biological tissue, most optical functional imaging methods are limited to the surface of the brain or have poor resolution. In this work, a single fiber optical system with zero source-detector separation is presented. The system is designed for measuring the oxygen saturation of deep brain structures by implanting the small diameter fiber probe into the tissue of interest. The system measures oxygen saturation using a steady-state spectroscopy method based on the absorption properties of oxy-hemoglobin and deoxy-hemoglobin. This thesis covers: (a) system design, including the optical simulation, system components and performance; (b) Monte Carlo simulations for wavelength determination, depth penetration and the received signal; (c) quantification method for the single fiber system; and (d) experimental results in a tissue phantom.Item Open Access Aerothermodynamic Measurements in Hypersonic Non-Equilibrium Flows(2022-11-10) McDougall, Connor Charles; Johansen, Craig; Murari, Kartikeya; Morton, Christopher; Ghaemi, Sina; Davidsen, Joern; Bauwens, LucHigh enthalpy arc-jets are unique facilities particularly suited for producing complex flows in the aerospace field, such as the aerothermodynamics of a re-entry vehicle. Arc-jets are often used to evaluate important design factors that include heat shield materials and vehicle design. Characterization of these facilities is important, as studies often aim to match specific in-flight environments during experiments. Due to the complex environment produced by an arc-jet, with effects such as thermodynamic and chemical non-equilibrium occurring in the flow, characterization experiments are significantly more difficult than in conventional blow-down wind tunnels. The current work aims to characterize an arc-jet facility through spatially-resolved measurements of flow unsteadiness, temperature, and velocity. To achieve this goal, a non-intrusive imaging technique called “planar laser-induced fluorescence” was performed in the NASA Langley Hypersonic Materials Environmental Test System arc-jet facility. The experimental data was analysed to produce the quantitative measurements in multiple regions of the flow around a blunt body specimen. A three-temperature low fidelity numerical solver was created to simulate the flow in order to investigate thermal non-equilibrium effects occurring outside the imaging region in the arc-jet nozzle. Unsteadiness in the test section of the arc-jet was minimized by analyzing a subset of data assessing the gas injection configuration. Radial velocity, rotational temperature and translational temperature measurements are provided that can be used to validate future computational studies. The temperature measurements revealed rotational non-equilibrium occurring behind the bow-shock near the specimen surface. Computational results show the facility is capable of producing thermal non-equilibrium flow in the arc-jet nozzle. This work provides the first experimental and computational evidence of thermal trans-rotational non-equilibrium occurring in multiple regions of this arc-jet facility. Significant improvements to the methodology are also identified as recommendations for future arc-jet characterization studies.Item Open Access Approaches to Reduce Clutter and Enhance Robustness of Vortex Extraction in Flow Visualization(2017) Padmesh, Kavya; Hu, Yaoping; Smith, Mike; Murari, KartikeyaOver the past few decades, extraction and visualization of flow features like vortices has gained tremendous importance and is employed in numerous applications. Several vortex detectors are available in literature that can identify vortices in most empirical and computational datasets. However, despite these efforts, uncertainties in empirical measurements often results in undesired vectors that cause clutter in visualization. Clutter would obscure vortex features and make it hard to understand complex flow behavior. Additionally, floating-point errors in vortex detector computations lead to false positives in vortex extraction. This thesis aims to solve aforementioned problems by implementing - a pre-processing technique to filter undesired vectors from empirical data and a threshold estimation technique to reduce the effect of floating-point errors in vortex extraction. Proposed methodologies are tested on several flow datasets of various sizes and turbulence intensities. Results indicate enhanced visualization by reducing clutter; also, they confirm improved robustness in vortex extraction.Item Embargo Automated Video-Based Rodent Behavior Analysis(2024-01-30) Le, Van Anh; Murari, Kartikeya; Forkert, Nils Daniel; Yanushkevich, Svetlana; Bento, Mariana Pinheiro; Ravichandran, AvinashRodents represent more than 95% of the laboratory animals used in preclinical and neuroscience research. Mouse behavior analysis is an important step to evaluate disease states and normal brain processes. This thesis focuses on developing automatic video-based mouse behavior analysis tools, which allow high throughput assessments and alleviate the limitations of manual analysis. Particularly, we investigated multiple machine-learning based approaches to fill the gaps of existing studies regarding rodent behavior measurements and create reliable computer-assisted frameworks. Firstly, we introduced MaSoMoTr which is a markerless mice tracking tool for social experiments. The tracking workflow incorporated deep-learning-based techniques with conventional handcrafted tracking methods to simultaneously track two mice of the same appearance in controlled settings. The proposed method achieved significant improvement compared to the state-of-the-art pose-estimation-based tracking frameworks. Following that, we developed a social behavior recognition system integrating our tracking tool to identify a set of mouse behaviors in continuous videos recording two interacting mice. Datasets collected and annotated during these two studies have been made publicly available for further research and development. Finally, two approaches were proposed for automatically recognizing single mouse behaviors in two different settings. We investigated the possibility of extracting spatio-temporal features from single mouse recordings using a deep learning structure which combined a 3D convolutional network and a recurrent neural network with Long Short-Term Memory cells. These extracted features were tested to recognize 8 single mouse behaviors in videos belonging to the largest public single mouse dataset and attained promising performance. Next, we proposed a noninvasive video-based method for mouse sleep assessment. The results obtained were highly correlated with commonly used invasive methodsItem Open Access Bracing of Pectus Carinatum: A Quantitative Analysis(2017) Bugajski, Tomasz; Ronsky, Janet; Murari, Kartikeya; Lopushinsky, StevenPectus Carinatum (PC) presents as an overgrowth of costal cartilages resulting in a sternal protrusion. Treatment of PC is performed with a pectus carinatum orthosis (PCO) that compresses the protrusion. Injuries may arise when this PCO is over-tightened. For the first time, a force measurement system (FMS) was constructed that measured PCO forces. The purpose of this study was to determine if participants could accurately attain their clinically prescribed force (CF) over time, and if the protrusion stiffness (PS) influences the participant-applied forces (PF) and correction rate (CR). Results demonstrated that most PFs (75%) exceeded their associated CF (0.46-5.01 lbs). Further investigation is required to determine clinical significance. PS had a positive relationship with PF, but no relationship with CR. Future studies focusing on improved displacement measurements would enhance the ability to quantify PS. Developing a FMS to provide real-time feedback should also be considered to improve PCO efficacy.Item Open Access Compact Optical Sensing Systems for pH and Other Substances Detection - Theory and Implementation(2016) Cao, Muyun; Yadid-Pecht, Orly; Yadid-Pecht, Orly; Murari, Kartikeya; Chodavarapu, VamsyChemical detection is of importance in research and industry. Optical sensors based on contact imaging realize the chemical detection in compact, efficient and inexpensive ways. In the first project real-time optical pH sensor based on complementary metal–oxide–semiconductor (CMOS) contact imaging and microfluidics, an optical contact imaging sensor for pH detection with capillary microfluidics is proposed. The CMOS array detects the changes of light intensity after absorption by phenol red doped sol-gel filters while the level of absorbance corresponds to a pH value of the analyte. Deposition methods of sol-gel are optimized and compared. In the second project, real-time optical concentration sensor based on Raman scattering, CMOS contact imaging is presented. This biochemical optical sensor is designed for detecting the concentration of solutions. It is built with a laser diode, an optical filter, a sample holder and a commercial CMOS sensor.Item Open Access Computational Modeling of Electrical Cell-to-cell Interactions in Cardiac Tissue: Applications to Model Parameter Selection and Pacemaker Function(2017) Kaur, Jaspreet; Vigmond, Edward; Nygren, Anders; Di Martino, Elena; Hu, Yaoping; Murari, Kartikeya; Clancy, ColleenCell-to-cell interactions are important in determining the electrophysiological behavior of cardiac tissue. In this research, computer modeling is used to investigate the importance of these interactions in two different contexts: 1) how to adjust parameters in single cell models to accurately reproduce tissue behavior, and 2) determining requirements for successful conduction at the interface between different tissue types, specifically from the sinoatrial node (SAN) to the atrium. Membrane resistance (Rm), the inverse of the slope of the current-voltage (I/V) relationship for a cardiac myocyte, is an important determinant of electrical cell-to-cell interactions. Experimentally, Rm can be measured by applying a small current and measuring the resulting change in membrane voltage. To investigate the importance of Rm, a multi-objective genetic algorithm approach was developed for enhancing the fitting of action potentials (APs) in single cell models. Rm was fit at several points during the AP along with AP morphology. The results demonstrate that including Rm as a fitting criterion yields improved convergence, reduced variability in parameter estimates, and improved robustness, while specifically improving the ability of the model to reproduce tissue behavior. Bioengineered pacemakers are cellular constructs intended to replace the SAN pacemaker function. The interface between the SAN and atrium appears to have features designed to facilitate conduction. Depending on the species, these features involve gradual transitions (gradients) in ion channel densities and coupling conductance, or insulating boundaries with conduction at discrete exit points only. We used simulations to determine the importance of each of these features, with the aim to provide guidance to future development of bioengineered pacemakers. We found that gradients in ionic conductance (specifically ICaL) are required in rabbit SAN. There is narrow range of coupling for which the SAN is able to propagate towards atrium without coupling gradients. In canine SAN, these gradients support conduction. However, gradients are not required, provided conduction from SAN to atrium is restricted to discrete exit points. This suggests two possible strategies for successful conduction at the interface between a bioengineered pacemaker and the atrium: 1) engineer the construct to have appropriate ionic current and intercellular coupling gradients, or 2) functionally insulate a homogeneous construct from the atrium with conduction only at discrete points.Item Open Access Correction of Motion Artifacts in Whole Heart Optical Mapping Data Using Ratiometry and Image Processing Techniques(2015-12-22) Rodriguez Ramirez, Marcela Patricia; Nygren, Anders; Lichti, Derek; Murari, Kartikeya; Duncan, Neil; Oudit, GavinCardiac optical mapping is a powerful tool to understand the electrophysiological mechanisms responsible for normal and abnormal cardiac rhythm. However, motion artifacts contained in the optical action potentials (APs) represent a major drawback of the technique. The calculation of electrophysiological parameters of interest such as action potential duration (APD) is challenged by the presence of motion artifacts. The use of chemical motion blockers is currently a preferable method to control motion artifacts, however these may affect the cardiac electrophysiology and consensus regarding their effects has not been reached. This thesis presents several key developments in techniques for motion artifact correction. Weighted ratiometry was implemented aiming to reduce motion artifacts in dual wavelength recordings. This thesis reports differences in shape and amplitude between motion artifacts contained in corresponding APs at both wavelengths. A new mathematical representation for motion artifacts is also presented to model such differences. Gross motion artifacts due to misalignment of the preparation with the imaging sensor across time are the result of the mechanical contraction of the heart. Landmark-based image registration is introduced to correct for such artifacts. It was concluded that the use of scale invariant feature transform (SIFT) is preferable for the datasets presented among the techniques evaluated for motion estimation. Several landmark-based non-rigid registration methods are studied in this thesis and their performance compared; coherence point drift (CPD) algorithms performed better for this application. Image registration resulted in good correction of gross motion artifacts, however artifacts with other origins must be handled separately. The combination of weighted ratiometry and landmark-based non-rigid registration is also evaluated as a composite method to further reduce artifacts that the techniques were not able to correct individually. The technique produced good correction and APDs calculated from the corrected datasets present low error values compared to a gold standard. APD modulation with 4-Aminopyridine served as a tool to corroborate that the combination of weighted ratiometry and image registration is able to reduce motion artifacts in APs to the point where APD can be calculated and the modulation of APD quantified.Item Open Access Cough Event Recognition Using Signal-Processing Based Feature Sets and Machine Learning, with Tri-Axial Accelerometer Sensor Worn at Multiple Body Points(2021-12-22) Doddabasappla Basavarajappa, Kruthi; Vyas, Rushi J.; Murari, Kartikeya; Yanushkevich, Svetlana N; Medeiros de Souza, RobertoHuman activity recognition (HAR) from time-series accelerometer and gyroscope sensor data has seen tremendous progress in recent years. Laying, standing, sitting, walking, walking down, and walking upstairs are the daily human activities that are commonly classified using sensor data. Cough is a common human activity and is also a symptom of various diseases including the novel coronavirus disease 2019 (COVID-19). Cough detection and classification are well investigated in recent literature to varying levels of success. But, in most of the studies, sensor data for cough activity is collected during still conditions such as sitting or standing and from a specific location such as chest and neck only. The body position of data recording considerably impacts the data, significantly affecting the classification accuracy. In our study, we place tri-axial accelerometer sensors at different spots on the human body where a smartphone or wearable device such as earphones or headphones are commonly worn. We studied the data with statistical and machine learning (ML) based signal processing methods to find the best accelerometer sensor position to detect coughing events accurately on the human body. Our study finds the most suitable sensor position for cough recognition considering the noise introduced by walking and considering different human heights. The proposed multi-band frequency-domain features such as Spectral Summation, Spectral Maximum, and Spectral Spread of acceleration signal offer higher classification accuracy for cough activity.Item Open Access Delta-Sigma Based Signal Processing Techniques for Broadband Radio Applications(2019-01-22) Ben Arfi, Anis; Ghannouchi, Fadhel M.; Sesay, Abu B.; Helaoui, Mohamed; Park, Chanwang; Murari, KartikeyaThe growing network coverage and the sharp increase in the number of devices in the wireless network have generated a great demand for browsing and accessing data, high-definition video, and streaming services without experiencing delays or interruptions. This is made possible by the high-speed connection and minimal latency achieved by efficient and reliable wireless network infrastructures. These networks are continuously evolving to serve huge numbers of users and satisfy the growing demand for data, while providing a good signal quality and maintaining a low power consumption. New techniques and designs of wireless devices are currently being developed to respond to the emerging applications requiring low power consumption, higher bandwidth, and minimum latency. This work focuses on enhancing the wireless transmitter performance by using the Delta-Sigma Modulation (DSM) technique. In fact, DSM-based transmitters have shown a relatively strong performance in terms of linearity and power efficiency. However, limitations on speed could degrade the overall performance and bandwidth. Research efforts have been focusing on DSMs as a promising solution to further enhance the overall efficiency of wireless devices. By proposing robust hardware implementation methods and preserving the linearity of the transmitter, the DSM topologies can match other existing transmitter topologies in terms of power efficiency while offering more flexibility when aiming at the design of Software Defined Radio (SDR) based transmitters. First, a general study on DSM basics and different DSM topologies is conducted. The study covers different types of DSMs classified by their transfer function, order and type: low-pass, high-pass, and band-pass. Different DSM-based transmitter topologies are presented, namely, the Cartesian, Polar, Envelope and the Complex Delta-Sigma Modulator (CxDSM) topologies. Also, the concept of using a multi-level DSM quantization has been investigated. Second, the impact of the undesired delays occurring during the hardware implementation is investigated. A post-compensation block is needed to cancel the effect of these delays and recover the correct DSM transfer function. Additionally, an implementation of an all-digital DSM-based transmitter for Software Defined Radio (SDR) applications was developed. The SDR transmitter is reconfigurable and has a lower latency compared to previous architectures. Furthermore, to improve the performance of DSMs and find a substitute for the COordinate Rotation DIgital Computer (CORDIC) based multi-level CxDSM, a multi-level complex quantizer implementation method on Digital Signal Processors (DSP) is proposed. The latter uses a look-up table (LUT) to generate quantized output samples. This method was proven to be robust and achieved a minimum latency. Third, an implementation of a multi-level DSM-based wireless transmitter is developed to preserve the power efficiency of the Switch Mode Power Amplifiers (SMPAs). For this purpose, a dual-branch three-level DSM was implemented and validated on a digital signal processing platform. Finally, a digital Intermediate-Frequency (IF) High-Pass DSM (HPDSM)-based transmitter is implemented and validated. By integrating a complex quantizer in the HPDSM-based topology, the performance is significantly improved. This topology maintains a low oversampling ratio, saves the processing resources while enhancing the quality of the output signal.Item Open Access Design and Development of a Multichannel Current-EMG System for Coherence Analysis(2016) Comaduran Marquez, Daniel; Nigg, Benno; Murari, Kartikeya; Von Tscharner, Vinzenz; Herzog, WalterElectromyography (EMG), the methodology to record muscle activity, has been unchanged for many years, with the use of instrumentation amplifiers (IAs). To overcome limitations of IAs when measuring EMG activity from pennate muscles, a transimpedance amplifier (TIA) has been proposed [1]. The TIA has the advantage of conserving all frequency information in the EMG signal. However, there are some limitations of the originally proposed current-amplifier. In this thesis, we present the design and development of an improved current-amplifier. Additionally, an isolation module was developed to record from multiple muscles simultaneously. The new current-amplifier was used in two experiments. The first experiment was conducted to test coherence, a metric that determines similarity in the frequency content of two signals, as an indicator of fatigue during a dynamic activity. The second experiment was conducted to test the ability of a biofeedback system to modulate coherence.Item Open Access Design and Implementation of a Magnitude Only Bio-Impedance Analyzer(2018-04-18) Al-Ali, Abdulwadood Abdullah Abdulwadood; Maundy, Brent J.; Murari, Kartikeya; Mintchev, Martin P.The increasing interest in the bio-impedance analysis in various fields has increased the demand for portable and low-cost impedance analyzers that can be used in the field. Simplifying the hardware is crucial to maintaining low-cost and portability, but this is not an easy task due to the need for accurate phase and magnitude measurements. This thesis proposes a new measurement technique that replaces the need to measure the phase by using a software algorithm to extract the phase from the magnitude information. The algorithm which is based on a modified Kramers-Kronig transforms was implemented and tested first using MATLAB, where error and noise analysis on the algorithm were done. Furthermore, the algorithm was written using a python code, and a full Bio-impedance measurement system was proposed to be used for fruit quality control which is receiving increasing attention as an important application of bio-impedance measurements, for being a non-invasive technique. The Final design which was implemented on a printed circuit board (PCB), had a final cost of around $95 CAD and drew a maximum current of around 88mA which satisfies the requirement of a low-cost and low-power device respectively. The device was then tested with passive components and several fruit samples to show that it can effectively monitor fruit samples impedance in the range 100 Ohm-280 kOhm, and a frequency range 1 Hz-10 MHz which is higher than any other work in the literature. The proposed portable bio-impedance analyzers were then used to study the ageing effect of some strawberries samples on their bio-impedance, and the results showed that the device could be used in such an application.Item Open Access Design and Implementation of Single Transistor Active Filters(2017) Poddar, Neethila Nabanita; Maundy, Brent JP; Murari, Kartikeya; Lachapelle, Gerard JulesThis thesis investigates the design of single transistor second order active filters. Four general topologies are presented, each with a two port network surrounded by three impedances that form a T-network. From the topologies, four transfer functions are derived which are further simplified by replacing the two port transmission matrix parameters with those of an ideal MOS. An exhaustive MAPLE search code is used to generate all possible second order filters. The search is carried out on the four general transfer functions, considering all possible impedance combinations. Design procedures of selected filters are shown and verified by Cadence Spectre simulations and experimental measurements. Based on the single transistor second order filters, active realizations of higher order filters are explored. A fourth order bandpass Chebyshev filter and a fourth order Comb filter are presented. Simulation and experimental results of the designed filters are shown and compared with the theoretical ones.Item Open Access Developing a microfluidic-microwave platform for real-time, non-invasive and sensitive monitoring of pathogens and antibiotic susceptibility testing(2020-06-25) Narang, Rakesh; Sanati-Nezhad, Amir; Murari, Kartikeya; Zarifi, Mohammad H,Microfluidics and microelectromechanical systems (MEMS) are areas of studies that have become highly valued for their point-of-care (POC) and high-throughput potential, particularly in healthcare and biomedical applications. However, lab-on-a-chip devices often require supplementary equipment to operate such as pumps, computers, analyzers, valves, etc. This creates a lab-around-a-chip environment. Therefore, capillary fluidics has been developed to eliminate the need of some external machines such as pumps and valves. By capitalizing upon geometric changes to create a specific hydrodynamic profile, capillary fluidics creates an autonomous fluid delivery system for microfluidics which renders devices simple to use in POC environments. Furthermore, it is easily implemented with various sensory methods, such as optical, electrochemical or microwave sensing. One application in which capillary fluidics can vastly improve the quality of service is infection diagnosis and antibiotic susceptibility testing. Due to issues with infection diagnosis and outdated antibiotic susceptibility testing (AST) methods, physicians are over-prescribing broad-spectrum antibiotics. This coupled with patients’ non-compliance in antibiotic administration gives pathogens the ability to evolve a resistance to antibiotics. The root of the underlying issue creates a critical need to focus on bacterial infection diagnosis and AST, as contemporary practices require up to two weeks, are expensive, labor intensive, and lack the potential for point-of-care testing. Therefore, diagnosis and AST are not performed in most cases leading to broad-spectrum antibiotic prescriptions being overused. For the application of monitoring pathogens and performing AST, microwave sensing was selected for highly sensitive and relatively inexpensive implementation. Microwave resonators generate electrical fields and detect dielectric shifts within their sensing zone to characterize bioassays in a real-time, sensitive and non-invasive manner. Currently, microwave sensors are being optimized with multiple resonators to further optimize sensitivity and selectivity for biomedical applications. This makes microwave sensing an attractive approach to couple with capillary microfluidics for infection diagnosis and AST. This work aims to provide a proof of concept in coupling capillary microfluidics with planar microwave resonators to create a sensing platform to monitor the growth and antibiotic susceptibility of E. coli.Item Open Access Developing Rapid Screening Tools for Predicting Nanomedicine Transport Limitations(2016) Sarsons, Christopher; Rinker, Kristina; Grainger, David; Kallos, Michael; Cramb, David; Trifkovic, Milana; Murari, KartikeyaNanomedicines represent the future of medicine. Targeted therapies promise to increase treatment efficacy while simultaneously reducing side effects. However, despite two decades of dedicated research, this paradigm shift has found little clinical traction. Partly to blame is the multitude of off-target sinks and degrading factors that limit delivery efficiency. Rapid, cost effective, in vitro models may be able to screen novel nanomedicines for their susceptibility to these transport limitations. This thesis focuses on studying nanoparticle transport in two specific domains: endothelium interactions and extracellular matrix diffusion, utilizing in vitro platforms. Laser-scanning confocal microscopy and associated image analysis techniques allow fluorescently-labelled, cell-associated nanoparticles to be quantified. However, image analysis procedures lack standardization. Endothelial cells were exposed to fluorescent nanoparticles to investigate whether different image analysis techniques could impact particle quantification. Significant differences were found when fluorescence quantification and image normalization methods were varied, as well as when image projections were analysed. Fluid flow forces impact nanoparticle interactions with the endothelium. The association of quantum dots with human endothelial cells was studied after flow preconditioning in a parallel plate flow chamber at various flow magnitudes. The results were compared with distribution patterns of quantum dots in zebrafish embryo vasculature. It was found that quantum dots preferentially accumulate in lower flow vessels, and associate more with cells that have undergone lower flow preconditioning. A novel platform was developed to study the transport of gold nanoparticles in extracellular matrix. It was found that matrix density and particle diameter impact the matrix diffusion of particles. These results were supported by a tumour-bearing murine model and in silico predictions of particle behaviour. Characterization of these three models lead to a decision matrix to select nanoparticle properties based on patient-specific pathophysiology. The novel platform was further applied to understanding the effect of polyethylene glycol surface functionalization on liposome diffusion in extracellular matrix. It was found that polymer conformation is an important driver of particle-matrix interactions. Together this work provides new insights into nanoparticle transport limitations, showcases the predicative value of in vitro modelling of particle transport and offers new tools towards increasing the clinical translation of nanomedicines.Item Open Access Development and Characterization of an LED-Based Light Source for High-Speed Schlieren Imaging(2016-02-03) Lincoln, Daniel; Johansen, Craig; Murari, Kartikeya; De Visscher, Alex; Morton, Chris; Wood, DavidThis work investigates the viability of using a cost effective, 623 nm light emitting diode (LED) based light source for high-speed schlieren imaging. The pulser circuit used to drive the LED was characterized on the basis of input response, pulse train characteristics, and pulse energies. Relative brightness data was measured with a photodiode and further examined within a schlieren system. Flow images of decaying, cylindrical shocks were obtained with the LED system and benchmarked against a high intensity discharge (HID) lamp. It was found that the LED could be overdriven up to 20 times the rated current while generating down to 100 ns pulses at up to a 1 MHz repetition rate. Moreover, although the LED system produced higher signals and reduced exposure times, similar image detail was observed for each light source. However, the LED exhibited a distinct advantage over the HID lamp in terms of image blur.Item Open Access Development and Validation of a Current-Based EEG System for Tangential Current Measurement(2021-09-10) Comaduran Marquez, Daniel; Murari, Kartikeya; Sotero-Diaz, Roberto C.; Federico, PaoloVoltage-based electroencephalography (vEEG) and magnetoencephalography (MEG) are among the state-of-the-art non-invasive methodologies to study the electrophysiology of the human brain. Both methodologies offer high temporal but limited spatial resolution. vEEG and MEG are sensitive to radially and tangentially oriented dipoles in the brain, respectively. This complementary information improves the achievable spatial resolution when used simultaneously in source localization applications (e.g., locating epilepsy foci). However, MEG is not as easily accessible as vEEG. The initial setup cost of an MEG system is in the order of millions of US dollars (USD), and the yearly operational cost can be hundreds of thousands of USD. Conversely, a high-end vEEG system can be acquired for tens of thousands of USD and require minimal maintenance. In some topologies, vEEG can measure from tangential dipoles, but suffers from fundamental limitations regarding signal strength. To address the technological need for a more accessible technology than MEG that can measure tangential dipoles in the brain, I developed a current-based EEG (cEEG) system. The cEEG has a front-end transimpedance amplifier to measure currents that are caused by tangential dipoles. A one-channel cEEG amplifier was conceptualized, designed, simulated, implemented, and characterized for validating the proposed current-based technology. The characterization met design goals set to reliably measure brain currents. Using phantom and simulation models, I found that cEEG is mostly influenced by tangential dipoles. Further, the cEEG was used to measure alpha waves during a resting, and steady-state visual evoked potentials paradigms to measure brain activity from ten healthy individuals. Statistical analysis of the experimental data showed that the cEEG could effectively measure brain activity. Towards the development of a multichannel system, a second cEEG was developed with a microcontroller for on-board digitization of the amplified and filtered signal. This implementation allows the cEEG to have isolated power supplies, which are required if multiple amplifiers were to be used. cEEG systems open up the possibility to understand brain activity from a different perspective in research and clinical applications.Item Open Access Development of a Miniaturized Biphasic Constant-Current Charge-Balanced Stimulator for Freely Moving Animals(2016-02-03) Acosta Calvillo, Adan Isaac; Murari, Kartikeya; Vyas, Rushi; Menon, Bijoy; Rival, David; Nowicki, EdwinNeurological disorders are diseases that target the central and peripheral nervous system. These disorders include Alzheimer, Parkinson’s disease and other dementias. Common treatment for some neurological disorders are drugs and when this method is not so effective, the next method is electrical stimulation, where a Deep Brain Stimulation (DBS) device is surgically implanted. In spite of extensive application in humans and research in animals, the mechanisms of DBS remain unclear. This thesis presents a miniaturized discrete system for long-term, biphasic constant current, charge balanced stimulation for DBS research in small animals with independently programmable anodic and cathodic currents and pulse widths, frequency, pulse order and inter pulse interval. It features a single current source and an H-bridge for setting current direction. The system is highly customizable, permitting trade-off between voltage compliance and the range, resolution and accuracy of currents and between power consumption and temporal resolution with minimal hardware modification.Item Open Access Development of an Experimental Platform to Enable Ultrasound Neuromodulation Studies(2022-05-09) Loree-Spacek, Jak; Pichardo, Samuel; Kiss, Zelma; McGirr, Alexander; Curiel, Laura; Murari, KartikeyaFocused ultrasound (FUS) neuromodulation is the delivery of concentrated mechanical energy into central nervous tissue at low intensity (a few W per cm^2; about as intense as imaging ultrasound, and not sufficiently intense to cause heating) with the goal of eliciting a functional change. It is of interest to applied and clinical scientists as a prospective non-invasive therapeutic intervention; it is also applicable to basic scientists as a tool for in vivo brain mapping. This work details the development of a device and accompanying system that enables the study of ultrasound-mediated neuromodulation in brain tissue samples in a setting with concurrent electrophysiology. We use a novel ultrasound focusing technique based on principles of acoustic reflection, and the first research chapter discusses the development and integration of this focusing technique. To develop and refine our design, I used finite-element modeling and iterative computer optimization techniques. The concordance of these in silico techniques with reality was verified with prototypes and hydrophone acoustic field measurements. Subsequently, several production-quality ultrasound units were produced to the specifications determined by modeling; these units exhibited performance improvements based on the results from testing prototypes, and they were characterized in terms of efficiency, electrical impedance, and ultrasonic pressure field shape. We used two independent methods to verify the absolute acoustic intensity output by our device: radiation-force absorber measurements in conjunction with wide-field hydrophone scans, and then later a calibrated hydrophone. The second research chapter of this manuscript describes the application of our system to neuroscientific experiments: I detail how we obtained early data pertaining to the ability of pulsed FUS to modulate field potential activity in acute animal brain slices. We observed an intensity-dependent modulation effect in a majority of slices tested (>50%, n=44); however, this effect was determined to be dominated by a confound and unlikely to be physiological. This course of study explored and evaluated a novel technique for obtaining an ultrasound focus; it also yielded a system that enables further experiments into interactions between FUS and brain tissue. This manuscript, the devices resulting from the work, and the documentation included in the appendices will enable continued investigations into ultrasound neuromodulation at the University of Calgary.