Matching Items (53)
Description
Optogenetics presents the ability to control membrane dynamics through the usage of transfected proteins (opsins) and light stimulation. However, as the field continues to grow, the original biological and stimulation tools used have become dated or limited in their uses. The usage of Organic Light Emitting Diodes (OLEDs) in optical stimulation offers greater resolution, finer control of pixel arrays, and the increased functionality of a flexible display at the cost of lower irradiance power density. This study was done to simulate methods using genetic and optical tools towards decreasing the threshold irradiance needed to initiate an action potential in a ChR2 expressing neuron. Simulations show that pulsatile stimulation can decrease threshold irradiances by increasing the overall duration of stimulus while keeping individual pulse durations below 5 ms. Furthermore, the redistribution of Channelrhodopsin-2 (ChR2) to the apical dendrites and a change in wavelength to 625 nm both result in lower threshold irradiances. However, the model used has many discrepancies and has room for improvement in areas such as the light distribution model and ChR2 dynamics. The simulations run with this model however still present valuable insight and knowledge towards the usage of new stimulation methods and revisions on existing protocols.
ContributorsKyeh, James (Author) / Muthuswamy, Jitendran (Thesis director) / Crook, Sharon (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
It is unknown which regions of the brain are most or least active for golfers during a peak performance state (Flow State or "The Zone") on the putting green. To address this issue, electroencephalographic (EEG) recordings were taken on 10 elite golfers while they performed a putting drill consisting of hitting nine putts spaced uniformly around a hole each five feet away. Data was collected at three time periods, before, during and after the putt. Galvanic Skin Response (GSR) measurements were also recorded on each subject. Three of the subjects performed a visualization of the same putting drill and their brain waves and GSR were recorded and then compared with their actual performance of the drill. EEG data in the Theta (4 \u2014 7 Hz) bandwidth and Alpha (7 \u2014 13 Hz) bandwidth in 11 different locations across the head were analyzed. Relative power spectrum was used to quantify the data. From the results, it was found that there is a higher magnitude of power in both the theta and alpha bandwidths for a missed putt in comparison to a made putt (p<0.05). It was also found that there is a higher average power in the right hemisphere for made putts. There was not a higher power in the occipital region of the brain nor was there a lower power level in the frontal cortical region during made putts. The hypothesis that there would be a difference between the means of the power level in performance compared to visualization techniques was also supported.
ContributorsCarpenter, Andrea (Co-author) / Hool, Nicholas (Co-author) / Muthuswamy, Jitendran (Thesis director) / Crews, Debbie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This study aimed to quantify glare induced into the NICU through phototherapy devices commonly used to treat neonatal jaundice. The blue light associated with the devices can cause a number of physiological affects including melatonin suppression, disturbances of one's circadian rhythm, and has the potential to lead to risk factors of age-related macular degeneration (AMD) in the long term. The study found that the phototherapy device tested emitted a sufficient amount of light to be considered 'disturbing' using the DeBoer scale. Due to this, phototherapy devices in the future should take into consideration the minimization of light emitted which is not directly treating the infant on the device to prevent potential physiological effects that nurses may experience.
ContributorsSnelling, Timothy Michael (Author) / Muthuswamy, Jitendran (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The effect of three different drug modulators on the electrophysiological response of Aplysia neurons was observed through the use of extracellular and intracellular recordings. Extracellular recordings captured the effects of magnesium chloride and glutamate at a variety of concentrations for each. Intracellular recordings displayed the effects of magnesium chloride, glutamate, and GABA for two concentrations each. For extracellular recordings, the average firing rate, average peak-to-peak voltage, average SNR, and sorted units were considered. For intracellular recordings, average firing rate, average peak voltage, and average resting potential were considered. Significance of data could not be determined using statistical analysis due to having a sample size of 1 for every experiment.
ContributorsEyster, Kyle (Co-author) / Moore, Amanda (Co-author) / Muthuswamy, Jitendran (Thesis director) / Sadleir, Rosalind (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
For my honors thesis, I developed a proof of concept alpha prototype of a biomedical device for detection of cerebrospinal fluid leaks during spinal surgery. Cerebrospinal fluid leaks are a consequence of tears in the dura mater of the spinal cord and can result in potentially life-threatening conditions and are overall a large burden not only on the patient but upon the clinical teams managing the patient postoperatively. What I created was an optical sensor that I programmed to be sensitive to detecting green wavelength light. The device would ideally be attached to surgical drain tubing and used in conjunction with fluorescein (a green fluorescent dye) infused lumbar punctures into the spinal canal of patients. As the dye circulates through the spinal cord, any tears in the dura mater would cause the fluorescein to leak out with cerebrospinal fluid into the incision site. This fluid may then be collected by the surgical drain where the sensor may detect the fluorescein, triggering a buzzer response that would notify the patient or the surgeons of an ongoing leak that requires repair. The time I spent on my thesis involved sensor validation to ensure it could differentiate between colors, testing the sensor's color sensitivity by performing a fluorescein aliquot, and running proof of concept testing that could show the sensor can detect fluorescein drain tubing and provide an adequate response. The sensor was able to differentiate between varying concentrations of fluorescein in solution and provided exceptional results in its proof-of-concept testing. Next steps will be to re-run the sensor validation study with different dyes as well as consolidating the device's electrical hardware onto a single circuit board as development of beta and gamma prototypes move forward.
ContributorsAlam, Framarz (Author) / Muthuswamy, Jitendran (Thesis director) / Bohl, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Abstract Modern imaging techniques for sciatic nerves often use imaging techniques that can clearly find myelinated axons (Group A and Group B and analyze their properties, but have trouble with the more numerous Remak Fibers (Group C). In this paper, Group A and B fibers are analyzed while also analyzing Remak fibers using osmium tetroxide staining and imaging with the help of transmission electron microscopy. Using this method, nerves had various electrical stimuli attached to them and were analyzed as such. They were analyzed with a cuff electrode attached, a stimulator attached, and both, with images taken at the center of the nerve and the ends of them. The number and area taken by the Remak fibers were analyzed, along with the g-ratios of the Group A and B fibers. These were analyzed to help deduce the overall health of the fibers along with vacuolization, and mitochondria available. While some important information was gained from this evaluation, further testing has to be done to improve the myelin detection system, along with analyzing the proper and necessary Remak fibers and the role they play. The research tries to thoroughly look at the necessary material and find a way to use it as a guide to further experimentation with electrical stimuli, and notes the differences found within and without various groups, various points of observation, and various stimuli as a whole. Nevertheless, this research allows a strong look into the benefits of transmission electron microscopy and the ability to assess electrical stimulation from these points.
ContributorsNambiar, Karthik (Author) / Muthuswamy, Jitendran (Thesis director) / Towe, Bruce (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
An improved system for wireless neurostimulation was investigated through the design and development of sub-millimeter piezoelectric devices. The devices build on prior work in the lab, which was limited by device size and required surgical implantation. A method of manufacturing sub-mm devices was developed, and utilized to construct this new design. The device frequency response was characterized and its resonant modes and output voltages determined through a Fast Fourier Transform. The fundamental thickness mode frequency was found to be 15.4MHz with a corresponding 10.25mV amplitude, and a longitudinal resonant frequency of 3.1Mhz with a corresponding 2.2mV amplitude across a 50Ω resistor. The high miniaturization of the device holds promise for future work for creating an injectable, wireless system for the treatment of neurological disorders.
ContributorsCatchings, Michael Thomas (Author) / Towe, Bruce (Thesis director) / Muthuswamy, Jitendran (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Long-term monitoring of deep brain structures using microelectrode implants is critical for the success of emerging clinical applications including cortical neural prostheses, deep brain stimulation and other neurobiology studies such as progression of disease states, learning and memory, brain mapping etc. However, current microelectrode technologies are not capable enough of reaching those clinical milestones given their inconsistency in performance and reliability in long-term studies. In all the aforementioned applications, it is important to understand the limitations & demands posed by technology as well as biological processes. Recent advances in implantable Micro Electro Mechanical Systems (MEMS) technology have tremendous potential and opens a plethora of opportunities for long term studies which were not possible before. The overall goal of the project is to develop large scale autonomous, movable, micro-scale interfaces which can seek and monitor/stimulate large ensembles of precisely targeted neurons and neuronal networks that can be applied for brain mapping in behaving animals. However, there are serious technical (fabrication) challenges related to packaging and interconnects, examples of which include: lack of current industry standards in chip-scale packaging techniques for silicon chips with movable microstructures, incompatible micro-bonding techniques to elongate current micro-electrode length to reach deep brain structures, inability to achieve hermetic isolation of implantable devices from biological tissue and fluids (i.e. cerebrospinal fluid (CSF), blood, etc.). The specific aims are to: 1) optimize & automate chip scale packaging of MEMS devices with unique requirements not amenable to conventional industry standards with respect to bonding, process temperature and pressure in order to achieve scalability 2) develop a novel micro-bonding technique to extend the length of current polysilicon micro-electrodes to reach and monitor deep brain structures 3) design & develop high throughput packaging mechanism for constructing a dense array of movable microelectrodes. Using a combination of unique micro-bonding technique which involves conductive thermosetting epoxy’s with hermetically sealed support structures and a highly optimized, semi-automated, 90-minute flip-chip packaging process, I have now extended the repertoire of previously reported movable microelectrode arrays to bond conventional stainless steel and Pt/Ir microelectrode arrays of desired lengths to steerable polysilicon shafts. I tested scalable prototypes in rigorous bench top tests including Impedance measurements, accelerated aging and non-destructive testing to assess electrical and mechanical stability of micro-bonds under long-term implantation. I propose a 3D printed packaging method allows a wide variety of electrode configurations to be realized such as a rectangular or circular array configuration or other arbitrary geometries optimal for specific regions of the brain with inter-electrode distance as low as 25 um with an unprecedented capability of seeking and recording/stimulating targeted single neurons in deep brain structures up to 10 mm deep (with 6 μm displacement resolution). The advantage of this computer controlled moveable deep brain electrodes facilitates potential capabilities of moving past glial sheath surrounding microelectrodes to restore neural connection, counter the variabilities in signal amplitudes, and enable simultaneous recording/stimulation at precisely targeted layers of brain.
ContributorsPalaniswamy, Sivakumar (Author) / Muthuswamy, Jitendran (Thesis advisor) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Arizona State University (Publisher)
Created2016
Description
Gene delivery is a broadly applicable tool that has applications in gene therapy, production of therapeutic proteins, and as a study tool to understand biological pathways. However, for successful gene delivery, the gene and its carrier must bypass or traverse a number of formidable obstacles before successfully entering the cell’s nucleus where the host cell’s machinery can be utilized to express a protein encoded by the gene of interest. The vast majority of work in the gene delivery field focuses on overcoming these barriers by creative synthesis of nanoparticle delivery vehicles or conjugation of targeting moieties to the nucleic acid or delivery vehicle, but little work focuses on modifying the target cell’s behavior to make it more amenable to transfection.
In this work, a number of kinase enzymes have been identified by inhibition to be targets for enhancing polymer-mediated transgene expression (chapter 2), including the lead target which appears to affect intracellular trafficking of delivered nucleic acid cargo. The subsequent sections (chapters 3 and 4) of this work focus on targeting epigenetic modifying enzymes to enhance polymer-mediated transgene expression, and a number of candidate enzymes have been identified. Some mechanistic evaluation of these targets have been carried out and discussion of ongoing experiments and future directions to better understand the mechanistic descriptions behind the phenomena are discussed. The overall goal is to enhance non-viral (polymer-mediated) transgene expression by modulating cellular behavior for general gene delivery applications.
In this work, a number of kinase enzymes have been identified by inhibition to be targets for enhancing polymer-mediated transgene expression (chapter 2), including the lead target which appears to affect intracellular trafficking of delivered nucleic acid cargo. The subsequent sections (chapters 3 and 4) of this work focus on targeting epigenetic modifying enzymes to enhance polymer-mediated transgene expression, and a number of candidate enzymes have been identified. Some mechanistic evaluation of these targets have been carried out and discussion of ongoing experiments and future directions to better understand the mechanistic descriptions behind the phenomena are discussed. The overall goal is to enhance non-viral (polymer-mediated) transgene expression by modulating cellular behavior for general gene delivery applications.
ContributorsChristensen, Matthew David (Author) / Rege, Kaushal (Thesis advisor) / Nielsen, David (Committee member) / Green, Matthew (Committee member) / Haynes, Karmella (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2016
Description
From time immemorial, epilepsy has persisted to be one of the greatest impediments to human life for those stricken by it. As the fourth most common neurological disorder, epilepsy causes paroxysmal electrical discharges in the brain that manifest as seizures. Seizures have the effect of debilitating patients on a physical and psychological level. Although not lethal by themselves, they can bring about total disruption in consciousness which can, in hazardous conditions, lead to fatality. Roughly 1\% of the world population suffer from epilepsy and another 30 to 50 new cases per 100,000 increase the number of affected annually. Controlling seizures in epileptic patients has therefore become a great medical and, in recent years, engineering challenge.
In this study, the conditions of human seizures are recreated in an animal model of temporal lobe epilepsy. The rodents used in this study are chemically induced to become chronically epileptic. Their Electroencephalogram (EEG) data is then recorded and analyzed to detect and predict seizures; with the ultimate goal being the control and complete suppression of seizures.
Two methods, the maximum Lyapunov exponent and the Generalized Partial Directed Coherence (GPDC), are applied on EEG data to extract meaningful information. Their effectiveness have been reported in the literature for the purpose of prediction of seizures and seizure focus localization. This study integrates these measures, through some modifications, to robustly detect seizures and separately find precursors to them and in consequence provide stimulation to the epileptic brain of rats in order to suppress seizures. Additionally open-loop stimulation with biphasic currents of various pairs of sites in differing lengths of time have helped us create control efficacy maps. While GPDC tells us about the possible location of the focus, control efficacy maps tells us how effective stimulating a certain pair of sites will be.
The results from computations performed on the data are presented and the feasibility of the control problem is discussed. The results show a new reliable means of seizure detection even in the presence of artifacts in the data. The seizure precursors provide a means of prediction, in the order of tens of minutes, prior to seizures. Closed loop stimulation experiments based on these precursors and control efficacy maps on the epileptic animals show a maximum reduction of seizure frequency by 24.26\% in one animal and reduction of length of seizures by 51.77\% in another. Thus, through this study it was shown that the implementation of the methods can ameliorate seizures in an epileptic patient. It is expected that the new knowledge and experimental techniques will provide a guide for future research in an effort to ultimately eliminate seizures in epileptic patients.
In this study, the conditions of human seizures are recreated in an animal model of temporal lobe epilepsy. The rodents used in this study are chemically induced to become chronically epileptic. Their Electroencephalogram (EEG) data is then recorded and analyzed to detect and predict seizures; with the ultimate goal being the control and complete suppression of seizures.
Two methods, the maximum Lyapunov exponent and the Generalized Partial Directed Coherence (GPDC), are applied on EEG data to extract meaningful information. Their effectiveness have been reported in the literature for the purpose of prediction of seizures and seizure focus localization. This study integrates these measures, through some modifications, to robustly detect seizures and separately find precursors to them and in consequence provide stimulation to the epileptic brain of rats in order to suppress seizures. Additionally open-loop stimulation with biphasic currents of various pairs of sites in differing lengths of time have helped us create control efficacy maps. While GPDC tells us about the possible location of the focus, control efficacy maps tells us how effective stimulating a certain pair of sites will be.
The results from computations performed on the data are presented and the feasibility of the control problem is discussed. The results show a new reliable means of seizure detection even in the presence of artifacts in the data. The seizure precursors provide a means of prediction, in the order of tens of minutes, prior to seizures. Closed loop stimulation experiments based on these precursors and control efficacy maps on the epileptic animals show a maximum reduction of seizure frequency by 24.26\% in one animal and reduction of length of seizures by 51.77\% in another. Thus, through this study it was shown that the implementation of the methods can ameliorate seizures in an epileptic patient. It is expected that the new knowledge and experimental techniques will provide a guide for future research in an effort to ultimately eliminate seizures in epileptic patients.
ContributorsShafique, Md Ashfaque Bin (Author) / Tsakalis, Konstantinos (Thesis advisor) / Rodriguez, Armando (Committee member) / Muthuswamy, Jitendran (Committee member) / Spanias, Andreas (Committee member) / Arizona State University (Publisher)
Created2016