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- All Subjects: Biomedical Engineering
- Creators: Santello, Marco
- Creators: Goryll, Michael
- Member of: Theses and Dissertations
Description
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
ContributorsRay, Tathagata (Author) / Youngbull, Cody (Thesis advisor) / Goryll, Michael (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2013
Description
Intracortical microstimulation (ICMS) within somatosensory cortex can produce artificial sensations including touch, pressure, and vibration. There is significant interest in using ICMS to provide sensory feedback for a prosthetic limb. In such a system, information recorded from sensors on the prosthetic would be translated into electrical stimulation and delivered directly to the brain, providing feedback about features of objects in contact with the prosthetic. To achieve this goal, multiple simultaneous streams of information will need to be encoded by ICMS in a manner that produces robust, reliable, and discriminable sensations. The first segment of this work focuses on the discriminability of sensations elicited by ICMS within somatosensory cortex. Stimulation on multiple single electrodes and near-simultaneous stimulation across multiple electrodes, driven by a multimodal tactile sensor, were both used in these experiments. A SynTouch BioTac sensor was moved across a flat surface in several directions, and a subset of the sensor's electrode impedance channels were used to drive multichannel ICMS in the somatosensory cortex of a non-human primate. The animal performed a behavioral task during this stimulation to indicate the discriminability of sensations evoked by the electrical stimulation. The animal's responses to ICMS were somewhat inconsistent across experimental sessions but indicated that discriminable sensations were evoked by both single and multichannel ICMS. The factors that affect the discriminability of stimulation-induced sensations are not well understood, in part because the relationship between ICMS and the neural activity it induces is poorly defined. The second component of this work was to develop computational models that describe the populations of neurons likely to be activated by ICMS. Models of several neurons were constructed, and their responses to ICMS were calculated. A three-dimensional cortical model was constructed using these cell models and used to identify the populations of neurons likely to be recruited by ICMS. Stimulation activated neurons in a sparse and discontinuous fashion; additionally, the type, number, and location of neurons likely to be activated by stimulation varied with electrode depth.
ContributorsOverstreet, Cynthia K (Author) / Helms Tillery, Stephen I (Thesis advisor) / Santos, Veronica (Committee member) / Buneo, Christopher (Committee member) / Otto, Kevin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb representation. In a previous study, Shi et al. (2013) examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and held their arm at various target locations in a frontal plane. Visual feedback was withheld in half the trials, though non-visual (i.e. somatic) feedback was available in all trials. Previous analysis showed that some of the neurons were tuned to limb position and that some neurons had their response modulated by the presence or absence of visual feedback. This modulation manifested in decreases in firing rate variability in the vision condition as compared to nonvision. The decreases in firing rate variability, as shown through decreases in both the Fano factor of spike counts and the coefficient of variation of the inter-spike intervals, suggested that changes were taking place in both trial-by-trial and intra-trial variability. I sought to further probe the source of the change in intra-trial variability through spectral analysis. It was hypothesized that the presence of temporal structure in the vision condition would account for a regularity in firing that would have decreased intra-trial variability. While no peaks were apparent in the spectra, differences in spectral power between visual conditions were found. These differences are suggestive of unique temporal spiking patterns at the individual neuron level that may be influential at the population level.
ContributorsDyson, Keith (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen I (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013
Description
Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present study investigated the effects of arm configuration on the interaction between planning noise and execution noise. Subjects performed reaching movements to three targets located in a frontal plane. At the starting position, subjects matched one of two desired arm configuration 'templates' namely "adducted" and "abducted". These arm configurations were obtained by rotations along the shoulder-hand axis, thereby maintaining endpoint position. Visual feedback of the hand was varied from trial to trial, thereby increasing uncertainty in movement planning and execution. It was hypothesized that 1) pattern of endpoint variability would be dependent on arm configuration and 2) that these differences would be most apparent in conditions without visual feedback. It was found that there were differences in endpoint variability between arm configurations in both visual conditions, but these differences were much larger when visual feedback was withheld. The overall results suggest that patterns of endpoint variability are highly dependent on arm configuration, particularly in the absence of visual feedback. This suggests that in the presence of vision, movement planning in 3D space is performed using coordinates that are largely arm configuration independent (i.e. extrinsic coordinates). In contrast, in the absence of vision, movement planning in 3D space reflects a substantial contribution of intrinsic coordinates.
ContributorsLakshmi Narayanan, Kishor (Author) / Buneo, Christopher (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Myoelectric control is lled with potential to signicantly change human-robot interaction.
Humans desire compliant robots to safely interact in dynamic environments
associated with daily activities. As surface electromyography non-invasively measures
limb motion intent and correlates with joint stiness during co-contractions,
it has been identied as a candidate for naturally controlling such robots. However,
state-of-the-art myoelectric interfaces have struggled to achieve both enhanced
functionality and long-term reliability. As demands in myoelectric interfaces trend
toward simultaneous and proportional control of compliant robots, robust processing
of multi-muscle coordinations, or synergies, plays a larger role in the success of the
control scheme. This dissertation presents a framework enhancing the utility of myoelectric
interfaces by exploiting motor skill learning and
exible muscle synergies for
reliable long-term simultaneous and proportional control of multifunctional compliant
robots. The interface is learned as a new motor skill specic to the controller,
providing long-term performance enhancements without requiring any retraining or
recalibration of the system. Moreover, the framework oers control of both motion
and stiness simultaneously for intuitive and compliant human-robot interaction. The
framework is validated through a series of experiments characterizing motor learning
properties and demonstrating control capabilities not seen previously in the literature.
The results validate the approach as a viable option to remove the trade-o
between functionality and reliability that have hindered state-of-the-art myoelectric
interfaces. Thus, this research contributes to the expansion and enhancement of myoelectric
controlled applications beyond commonly perceived anthropomorphic and
\intuitive control" constraints and into more advanced robotic systems designed for
everyday tasks.
Humans desire compliant robots to safely interact in dynamic environments
associated with daily activities. As surface electromyography non-invasively measures
limb motion intent and correlates with joint stiness during co-contractions,
it has been identied as a candidate for naturally controlling such robots. However,
state-of-the-art myoelectric interfaces have struggled to achieve both enhanced
functionality and long-term reliability. As demands in myoelectric interfaces trend
toward simultaneous and proportional control of compliant robots, robust processing
of multi-muscle coordinations, or synergies, plays a larger role in the success of the
control scheme. This dissertation presents a framework enhancing the utility of myoelectric
interfaces by exploiting motor skill learning and
exible muscle synergies for
reliable long-term simultaneous and proportional control of multifunctional compliant
robots. The interface is learned as a new motor skill specic to the controller,
providing long-term performance enhancements without requiring any retraining or
recalibration of the system. Moreover, the framework oers control of both motion
and stiness simultaneously for intuitive and compliant human-robot interaction. The
framework is validated through a series of experiments characterizing motor learning
properties and demonstrating control capabilities not seen previously in the literature.
The results validate the approach as a viable option to remove the trade-o
between functionality and reliability that have hindered state-of-the-art myoelectric
interfaces. Thus, this research contributes to the expansion and enhancement of myoelectric
controlled applications beyond commonly perceived anthropomorphic and
\intuitive control" constraints and into more advanced robotic systems designed for
everyday tasks.
ContributorsIson, Mark (Author) / Artemiadis, Panagiotis (Thesis advisor) / Santello, Marco (Committee member) / Greger, Bradley (Committee member) / Berman, Spring (Committee member) / Sugar, Thomas (Committee member) / Fainekos, Georgios (Committee member) / Arizona State University (Publisher)
Created2015
Description
This work explores how flexible electronics and display technology can be applied to develop new biomedical devices for medical, biological, and life science applications. It demonstrates how new biomedical devices can be manufactured by only modifying or personalizing the upper layers of a conventional thin film transistor (TFT) display process. This personalization was applied first to develop and demonstrate the world's largest flexible digital x-ray detector for medical and industrial imaging, and the world's first flexible ISFET pH biosensor using TFT technology. These new, flexible, digital x-ray detectors are more durable than conventional glass substrate x-ray detectors, and also can conform to the surface of the object being imaged. The new flexible ISFET pH biosensors are >10X less expensive to manufacture than comparable CMOS-based ISFETs and provide a sensing area that is orders of magnitude larger than CMOS-based ISFETs. This allows for easier integration with area intensive chemical and biological recognition material as well as allow for a larger number of unique recognition sites for low cost multiple disease and pathogen detection.
The flexible x-ray detector technology was then extended to demonstrate the viability of a new technique to seamlessly combine multiple smaller flexible x-ray detectors into a single very large, ultimately human sized, composite x-ray detector for new medical imaging applications such as single-exposure, low-dose, full-body digital radiography. Also explored, is a new approach to increase the sensitivity of digital x-ray detectors by selectively disabling rows in the active matrix array that are not part of the imaged region. It was then shown how high-resolution, flexible, organic light-emitting diode display (OLED) technology can be used to selectively stimulate and/or silence small groups of neurons on the cortical surface or within the deep brain as a potential new tool to diagnose and treat, as well as understand, neurological diseases and conditions. This work also explored the viability of a new miniaturized high sensitivity fluorescence measurement-based lab-on-a-chip optical biosensor using OLED display and a-Si:H PiN photodiode active matrix array technology for point-of-care diagnosis of multiple disease or pathogen biomarkers in a low cost disposable configuration.
The flexible x-ray detector technology was then extended to demonstrate the viability of a new technique to seamlessly combine multiple smaller flexible x-ray detectors into a single very large, ultimately human sized, composite x-ray detector for new medical imaging applications such as single-exposure, low-dose, full-body digital radiography. Also explored, is a new approach to increase the sensitivity of digital x-ray detectors by selectively disabling rows in the active matrix array that are not part of the imaged region. It was then shown how high-resolution, flexible, organic light-emitting diode display (OLED) technology can be used to selectively stimulate and/or silence small groups of neurons on the cortical surface or within the deep brain as a potential new tool to diagnose and treat, as well as understand, neurological diseases and conditions. This work also explored the viability of a new miniaturized high sensitivity fluorescence measurement-based lab-on-a-chip optical biosensor using OLED display and a-Si:H PiN photodiode active matrix array technology for point-of-care diagnosis of multiple disease or pathogen biomarkers in a low cost disposable configuration.
ContributorsSmith, Joseph T. (Author) / Allee, David (Thesis advisor) / Goryll, Michael (Committee member) / Kozicki, Michael (Committee member) / Blain Christen, Jennifer (Committee member) / Couture, Aaron (Committee member) / Arizona State University (Publisher)
Created2014
Description
Peripheral Vascular Disease (PVD) is a debilitating chronic disease of the lower extremities particularly affecting older adults and diabetics. It results in reduction of the blood flow to peripheral tissue and sometimes causing tissue damage such that PVD patients suffer from pain in the lower legs, thigh and buttocks after activities. Electrical neurostimulation based on the "Gate Theory of Pain" is a known to way to reduce pain but current devices to do this are bulky and not well suited to implantation in peripheral tissues. There is also an increased risk associated with surgery which limits the use of these devices. This research has designed and constructed wireless ultrasound powered microstimulators that are much smaller and injectable and so involve less implantation trauma. These devices are small enough to fit through an 18 gauge syringe needle increasing their potential for clinical use. These piezoelectric microdevices convert mechanical energy into electrical energy that then is used to block pain. The design and performance of these miniaturized devices was modeled by computer while constructed devices were evaluated in animal experiments. The devices are capable of producing 500ms pulses with an intensity of 2 mA into a 2 kilo-ohms load. Using the rat as an animal model, a series of experiments were conducted to evaluate the in-vivo performance of the devices.
ContributorsZong, Xi (Author) / Towe, Bruce (Thesis advisor) / Kleim, Jeffrey (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2014
Description
Biogenic silica nanostructures, derived from diatoms, possess highly ordered porous hierarchical nanostructures and afford flexibility in design in large part due to the availability of a great variety of shapes, sizes, and symmetries. These advantages have been exploited for study of transport phenomena of ions and molecules towards the goal of developing ultrasensitive and selective filters and biosensors. Diatom frustules give researchers many inspiration and ideas for the design and production of novel nanostructured materials. In this doctoral research will focus on the following three aspects of biogenic silica: 1) Using diatom frustule as protein sensor. 2) Using diatom nanostructures as template to fabricate nano metal materials. 3) Using diatom nanostructures to fabricate hybrid platform.
Nanoscale confinement biogenetic silica template-based electrical biosensor assay offers the user the ability to detect and quantify the biomolecules. Diatoms have been demonstrated as part of a sensor. The sensor works on the principle of electrochemical impedance spectroscopy. When specific protein biomarkers from a test sample bind to corresponding antibodies conjugated to the surface of the gold surface at the base of each nanowell, a perturbation of electrical double layer occurs resulting in a change in the impedance.
Diatoms are also a new source of inspiration for the design and fabrication of nanostructured materials. Template-directed deposition within cylindrical nanopores of a porous membrane represents an attractive and reproducible approach for preparing metal nanopatterns or nanorods of a variety of aspect ratios. The nanopatterns fabricated from diatom have the potential of the metal-enhanced fluorescence to detect dye-conjugated molecules.
Another approach presents a platform integrating biogenic silica nanostructures with micromachined silicon substrates in a micro
ano hybrid device. In this study, one can take advantages of the unique properties of a marine diatom that exhibits nanopores on the order of 40 nm in diameter and a hierarchical structure. This device can be used to several applications, such as nano particles separation and detection. This platform is also a good substrate to study cell growth that one can observe the reaction of cell growing on the nanostructure of frustule.
Nanoscale confinement biogenetic silica template-based electrical biosensor assay offers the user the ability to detect and quantify the biomolecules. Diatoms have been demonstrated as part of a sensor. The sensor works on the principle of electrochemical impedance spectroscopy. When specific protein biomarkers from a test sample bind to corresponding antibodies conjugated to the surface of the gold surface at the base of each nanowell, a perturbation of electrical double layer occurs resulting in a change in the impedance.
Diatoms are also a new source of inspiration for the design and fabrication of nanostructured materials. Template-directed deposition within cylindrical nanopores of a porous membrane represents an attractive and reproducible approach for preparing metal nanopatterns or nanorods of a variety of aspect ratios. The nanopatterns fabricated from diatom have the potential of the metal-enhanced fluorescence to detect dye-conjugated molecules.
Another approach presents a platform integrating biogenic silica nanostructures with micromachined silicon substrates in a micro
ano hybrid device. In this study, one can take advantages of the unique properties of a marine diatom that exhibits nanopores on the order of 40 nm in diameter and a hierarchical structure. This device can be used to several applications, such as nano particles separation and detection. This platform is also a good substrate to study cell growth that one can observe the reaction of cell growing on the nanostructure of frustule.
ContributorsLin, Kai-Chun (Author) / Ramakrishna, B.L. (Thesis advisor) / Goryll, Michael (Thesis advisor) / Dey, Sandwip (Committee member) / Prasad, Shalini (Committee member) / Arizona State University (Publisher)
Created2014
Description
Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of grip and load force rates during the period between initial contact with the object and object lift. However, this has not been validated in tasks that do not constrain digit placement. The purposes of this thesis were (1) to validate the hypothesis that force rate profiles are indicative of the control strategy used for object manipulation and (2) to test this hypothesis by comparing manipulation tasks performed with and without digit placement constraints. The first objective comprised two studies. In the first study an additional light or heavy mass was added to the base of the object. In the second study a mass was added, altering the object's center of mass (CM) location. In each experiment digit force rates were calculated between the times of initial digit contact and object lift. Digit force rates were fit to a Gaussian bell curve and the goodness of fit was compared across predictable and unpredictable mass and CM conditions. For both experiments, a predictable object mass and CM elicited bell shaped force rate profiles, indicative of feedforward control. For the second objective, a comparison of performance between subjects who performed the grasp task with either constrained or unconstrained digit contact locations was conducted. When digit location was unconstrained and CM was predictable, force rates were well fit to a bell shaped curve. However, the goodness of fit of the force rate profiles to the bell shaped curve was weaker for the constrained than the unconstrained digit placement condition. These findings seem to indicate that brain can generate an appropriate feedforward control strategy even when digit placement is unconstrained and an infinite combination of digit placement and force solutions exists to lift the object successfully. Future work is needed that investigates the role digit positioning and tactile feedback has on anticipatory control of object manipulation.
ContributorsCooperhouse, Michael A (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2011