Matching Items (21)
Filtering by
- All Subjects: Biomedical Engineering
- Genre: Masters Thesis
- Creators: Wang, Xiao
- Creators: Abbas, James
- Status: Published
Description
The object of this study is to charac terize the effect of focused ultrasound stimulation (FUS) on the rat ce rvix which has been observed to speed its ripening during pregnancy. Ce rvical ripening is required for successful fetal delivery. Timed-pregnant Sprague-Dawley rats (n=36) were used. On day 14 of gestation, the FUS system was placed on the body surface of the rat over the cervix and ultrasound energy was applied to cervix for variable times up to 1 hour in the control group, the FUS system was placed on rats but no energy was applied. Daily measurement of cervix light-induced florescence (LIF, photon counts of collagen x-bridge fluorescence) were made on days 16 of gestation and daily until spont-aneous delivery (day22) to estimate changes in cervical ripening. We found that pulses of 680 KHz ultrasound at 25 Hertz, 1 millisecond pulse duration at 1W/cm^2 applied for as little as 30 minutes would immediately afterwards show the cervix to hav e ripened to the degree seen just before delivery on day 22. Delivery times, fetal weights and viability were unaffected in the FUS-treated animals.
ContributorsLuo, Daishen (Author) / Towe, Bruce C (Thesis advisor) / Wang, Xiao (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to determine the speed of the plane. A clinical example would be that the flow of a patient's breath which could help determine the state of the patient's lungs. This project is focused on the flow-meter that are used for airflow measurement in human lungs. In order to do these measurements, resistive-type flow-meters are commonly used in respiratory measurement systems. This method consists of passing the respiratory flow through a fluid resistive component, while measuring the resulting pressure drop, which is linearly related to volumetric flow rate. These types of flow-meters typically have a low frequency response but are adequate for most applications, including spirometry and respiration monitoring. In the case of lung parameter estimation methods, such as the Quick Obstruction Method, it becomes important to have a higher frequency response in the flow-meter so that the high frequency components in the flow are measurable. The following three types of flow-meters were: a. Capillary type b. Screen Pneumotach type c. Square Edge orifice type To measure the frequency response, a sinusoidal flow is generated with a small speaker and passed through the flow-meter that is connected to a large, rigid container. True flow is proportional to the derivative of the pressure inside the container. True flow is then compared with the measured flow, which is proportional to the pressure drop across the flow-meter. In order to do the characterization, two LabVIEW data acquisition programs have been developed, one for transducer calibration, and another one that records flow and pressure data for frequency response testing of the flow-meter. In addition, a model that explains the behavior exhibited by the flow-meter has been proposed and simulated. This model contains a fluid resistor and inductor in series. The final step in this project was to approximate the frequency response data to the developed model expressed as a transfer function.
ContributorsHu, Jianchen (Author) / Macia, Narciso (Thesis advisor) / Pollat, Scott (Committee member) / Rogers, Bradley (Committee member) / Arizona State University (Publisher)
Created2013
Description
Gait and balance disorders are the second leading cause of falls in the elderly. Investigating the changes in static and dynamic balance due to aging may provide a better understanding of the effects of aging on postural control system. Static and dynamic balance were evaluated in a total of 21 young (21-35 years) and 22 elderly (50-75 years) healthy subjects while they performed three different tasks: quiet standing, dynamic weight shifts, and over ground walking. During the quiet standing task, the subjects stood with their eyes open and eyes closed. When performing dynamic weight shifts task, subjects shifted their Center of Pressure (CoP) from the center target to outward targets and vice versa while following real-time feedback of their CoP. For over ground walking tasks, subjects performed Timed Up and Go test, tandem walking, and regular walking at their self-selected speed. Various quantitative balance and gait measures were obtained to evaluate the above respective balance and walking tasks. Total excursion, sway area, and mean frequency of CoP during quiet standing were found to be the most reliable and showed significant increase with age and absence of visual input. During dynamic shifts, elderly subjects exhibited higher initiation time, initiation path length, movement time, movement path length, and inaccuracy indicating deterioration in performance. Furthermore, the elderly walked with a shorter stride length, increased stride variability, with a greater turn and turn-to-sit duration. Significant correlations were also observed between measures derived from the different balance and gait tasks. Thus, it can be concluded that aging deteriorates the postural control system affecting static and dynamic balance and some of the alterations in CoP and gait measures may be considered as protective mechanisms to prevent loss of balance.
ContributorsBalasubramanian, Shruthi (Author) / Krishnamurthi, Narayanan (Thesis advisor) / Abbas, James (Thesis advisor) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2014
Description
Although tremor, rigidity, and bradykinesia are cardinal symptoms of Parkinson's disease (PD), impairments of gait and balance significantly affect quality of life, especially as the disease progresses, and do not respond well to anti-parkinsonism medications. Many studies have shown that people with PD can walk better when appropriate cues are presented but, to the best of our knowledge, the effects of real-time feedback of step length and uprightness of posture on gait and posture have not been specifically investigated. If it can be demonstrated that real-time feedback can improve posture and gait, the resultant knowledge could be used to design effective rehabilitation strategies to improve quality of life in this population.
In this feasibility study, we have developed a treadmill-based experimental paradigm to provide feedback of step length and upright posture in real-time. Ten subjects (mean age 65.9 ± 7.6 years) with mild to moderate PD (Hoehn and Yahr stage III or below) were evaluated in their ability to successfully utilize real-time feedback presented during quiet standing and treadmill walking tasks during a single data collection session in their medication-on state. During quiet standing tasks in which back angle feedback was provided, subjects were asked to utilize the feedback to maintain upright posture. During treadmill walking tasks, subjects walked at their self-selected speed for five minutes without feedback, with feedback of back angle, or with feedback of step length. During walking tasks with back angle feedback, subjects were asked to utilize the feedback to maintain upright posture. During walking tasks with step length feedback, subjects were asked to utilize the feedback to walk with increased step length. During quiet standing tasks, measurements of back angle were obtained; during walking tasks, measurements of back angle, step length, and step time were obtained.
Subjects stood and walked with significantly increased upright posture during the tasks with real-time back angle feedback compared to tasks without feedback. Similarly, subjects walked with significantly increased step length during tasks with real-time step length feedback compared to tasks without feedback. These results demonstrate that people with PD can utilize real-time feedback to improve upright posture and gait.
In this feasibility study, we have developed a treadmill-based experimental paradigm to provide feedback of step length and upright posture in real-time. Ten subjects (mean age 65.9 ± 7.6 years) with mild to moderate PD (Hoehn and Yahr stage III or below) were evaluated in their ability to successfully utilize real-time feedback presented during quiet standing and treadmill walking tasks during a single data collection session in their medication-on state. During quiet standing tasks in which back angle feedback was provided, subjects were asked to utilize the feedback to maintain upright posture. During treadmill walking tasks, subjects walked at their self-selected speed for five minutes without feedback, with feedback of back angle, or with feedback of step length. During walking tasks with back angle feedback, subjects were asked to utilize the feedback to maintain upright posture. During walking tasks with step length feedback, subjects were asked to utilize the feedback to walk with increased step length. During quiet standing tasks, measurements of back angle were obtained; during walking tasks, measurements of back angle, step length, and step time were obtained.
Subjects stood and walked with significantly increased upright posture during the tasks with real-time back angle feedback compared to tasks without feedback. Similarly, subjects walked with significantly increased step length during tasks with real-time step length feedback compared to tasks without feedback. These results demonstrate that people with PD can utilize real-time feedback to improve upright posture and gait.
ContributorsJellish, Jeremy (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Thesis advisor) / Ingalls, Todd (Committee member) / Arizona State University (Publisher)
Created2014
Description
Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system can be used to diagnose fatal diseases, such as cancer, at an early stage. One proven method, CellCT, accomplishes 3D imaging by rotating a single cell around a fixed axis. However, some existing cell rotating mechanisms require either intricate microfabrication, and some fail to provide a suitable environment for living cells. This thesis develops a microvorterx chamber that allows living cells to be rotated by hydrodynamic alone while facilitating imaging access. In this thesis work, 1) the new chamber design was developed through numerical simulation. Simulations revealed that in order to form a microvortex in the side chamber, the ratio of the chamber opening to the channel width must be smaller than one. After comparing different chamber designs, the trapezoidal side chamber was selected because it demonstrated controllable circulation and met the imaging requirements. Microvortex properties were not sensitive to the chambers with interface angles ranging from 0.32 to 0.64. A similar trend was observed when chamber heights were larger than chamber opening. 2) Micro-particle image velocimetry was used to characterize microvortices and validate simulation results. Agreement between experimentation and simulation confirmed that numerical simulation was an effective method for chamber design. 3) Finally, cell rotation experiments were performed in the trapezoidal side chamber. The experimental results demonstrated cell rotational rates ranging from 12 to 29 rpm for regular cells. With a volumetric flow rate of 0.5 µL/s, an irregular cell rotated at a mean rate of 97 ± 3 rpm. Rotational rates can be changed by altering inlet flow rates.
ContributorsZhang, Wenjie (Author) / Frakes, David (Thesis advisor) / Meldrum, Deirdre (Thesis advisor) / Chao, Shih-hui (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2011
Description
Olecranon fractures account for approximately 10% of upper extremity fractures and 95% of them require surgical fixation. Most of the clinical, retrospective and biomechanical studies have supported plate fixation over other surgical fixation techniques since plates have demonstrated low incidence of reoperation, high fixation stability and resumption of activities of daily living (ADL) earlier. Thus far, biomechanical studies have been helpful in evaluating and comparing different plate fixation constructs based on fracture stability. However, they have not provided information that can be used to design rehabilitation protocols such as information that relates load at the hand with tendon tension or load at the interface between the plate and the bone. The set-ups used in biomechanical studies have included simple mechanical testing machines that either measured construct stiffness by cyclic loading the specimens or construct strength by performing ramp load until failure. Some biomechanical studies attempted to simulate tendon tension but the in-vivo tension applied to the tendon remains unknown. In this study, a novel procedure to test the olecranon fracture fixation using modern olecranon plates was developed to improve the biomechanical understanding of failures and to help determine the weights that can be safely lifted and the range of motion (ROM) that should be performed during rehabilitation procedures.
Design objectives were defined based on surgeon's feedback and analysis of unmet needs in the area of biomechanical testing. Four pilot cadaveric specimens were prepared to run on an upper extremity feedback controller and the set-up was validated based on the design objectives. Cadaveric specimen preparation included a series of steps such as dissection, suturing and potting that were standardized and improved iteratively after pilot testing. Additionally, a fracture and plating protocol was developed and fixture lengths were standardized based on anthropometric data. Results from the early pilot studies indicated shortcomings in the design, which was then iteratively refined for the subsequent studies. The final pilot study demonstrated that all of the design objectives were met. This system is planned for use in future studies that will assess olecranon fracture fixation and that will investigate the safety of rehabilitation protocols.
Design objectives were defined based on surgeon's feedback and analysis of unmet needs in the area of biomechanical testing. Four pilot cadaveric specimens were prepared to run on an upper extremity feedback controller and the set-up was validated based on the design objectives. Cadaveric specimen preparation included a series of steps such as dissection, suturing and potting that were standardized and improved iteratively after pilot testing. Additionally, a fracture and plating protocol was developed and fixture lengths were standardized based on anthropometric data. Results from the early pilot studies indicated shortcomings in the design, which was then iteratively refined for the subsequent studies. The final pilot study demonstrated that all of the design objectives were met. This system is planned for use in future studies that will assess olecranon fracture fixation and that will investigate the safety of rehabilitation protocols.
ContributorsJain, Saaransh (Author) / Abbas, James (Thesis advisor) / LaBelle, Jeffrey (Thesis advisor) / Jacofsky, Marc (Committee member) / Arizona State University (Publisher)
Created2015
Description
Progressive gait disorder in Parkinson's disease (PD) is usually exhibited as reduced step/stride length and gait speed. People with PD also exhibit stooped posture, which can contribute to reduced step length and arm swing. Since gait and posture deficits in people with PD do not respond well to pharmaceutical and surgical treatments, novel rehabilitative therapies to alleviate these impairments are necessary. Many studies have confirmed that people with PD can improve their walking patterns when external cues are presented. Only a few studies have provided explicit real-time feedback on performance, but they did not report how well people with PD can follow the cues on a step-by-step basis. In a single-session study using a novel-treadmill based paradigm, our group had previously demonstrated that people with PD could follow step-length and back angle feedback and improve their gait and posture during treadmill walking. This study investigated whether a long-term (6-week, 3 sessions/week) real-time feedback training (RTFT) program can improve overground gait, upright posture, balance, and quality of life. Three subjects (mean age 70 ± 2 years) with mild to moderate PD (Hoehn and Yahr stage III or below) were enrolled and participated in the program. The RTFT sessions involved walking on a treadmill while following visual feedback of step length and posture (one at any given time) displayed on a monitor placed in front of the subject at eye-level. The target step length was set between 110-120% of the step length obtained during a baseline non-feedback walking trial and the target back angle was set at the maximum upright posture exhibited during a quiet standing task. Two subjects were found to significantly improve their posture and overground walking at post-training and these changes were retained six weeks after RTFT (follow-up) and the third subject improved his upright posture and gait rhythmicity. Furthermore, the magnitude of the improvements observed in these subjects was greater than the improvements observed in reports on other neuromotor interventions. These results provide preliminary evidence that real-time feedback training can be used as an effective rehabilitative strategy to improve gait and upright posture in people with PD.
ContributorsBaskaran, Deepika (Author) / Krishnamurthi, Narayanan (Thesis advisor) / Abbas, James (Thesis advisor) / Honeycutt, Claire (Committee member) / Arizona State University (Publisher)
Created2017
Description
Recombinases are powerful tools for genome engineering and synthetic biology, however recombinases are limited by a lack of user-programmability and often require complex directed-evolution experiments to retarget specificity. Conversely, CRISPR systems have extreme versatility yet can induce off-target mutations and karyotypic destabilization. To address these constraints we developed an RNA-guided recombinase protein by fusing a hyperactive mutant resolvase from transposon TN3 to catalytically inactive Cas9. We validated recombinase-Cas9 (rCas9) function in model eukaryote Saccharomyces cerevisiae using a chromosomally integrated fluorescent reporter. Moreover, we demonstrated cooperative targeting by CRISPR RNAs at spacings of 22 or 40bps is necessary for directing recombination. Using PCR and Sanger sequencing, we confirmed rCas9 targets DNA recombination. With further development we envision rCas9 becoming useful in the development of RNA-programmed genetic circuitry as well as high-specificity genome engineering.
ContributorsStandage-Beier, Kylie S (Author) / Wang, Xiao (Thesis advisor) / Brafman, David A (Committee member) / Tian, Xiao-jun (Committee member) / Arizona State University (Publisher)
Created2018
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
Synthetic biology is a novel method that reengineers functional parts of natural genes of interest to build new biomolecular devices able to express as designed. There is increasing interest in synthetic biology due to wide potential applications in various fields such as clinics and fuel production. However, there are still many challenges in synthetic biology. For example, many natural biological processes are poorly understood, and these could be more thoroughly studied through model synthetic gene networks. Additionally, since synthetic biology applications may have numerous design constraints, more inducer systems should be developed to satisfy different requirements for genetic design.
This thesis covers two topics. First, I attempt to generate stochastic resonance (SR) in a biological system. Synthetic bistable systems were chosen because the inducer range in which they exhibit bistability can satisfy one of the three requirements of SR: a weak periodic force is unable to make the transition between states happen. I synthesized several different bistable systems, including toggle switches and self-activators, to select systems matching another requirement: the system has a clear threshold between the two energy states. Their bistability was verified and characterized. At the same time, I attempted to figure out the third requirement for SR – an effective noise serving as the stochastic force – through one of the most widespread toggles, the mutual inhibition toggle, in both yeast and E. coli. A mathematic model for SR was written and adjusted.
Secondly, I began work on designing a new genetic system capable of responding to pulsed magnetic fields. The operators responding to pulsed magnetic stimuli in the rpoH promoter were extracted and reorganized. Different versions of the rpoH promoter were generated and tested, and their varying responsiveness to magnetic fields was recorded. In order to improve efficiency and produce better operators, a directed evolution method was applied with the help of a CRISPR-dCas9 nicking system. The best performing promoters thus far show a five-fold difference in gene expression between trials with and without the magnetic field.
This thesis covers two topics. First, I attempt to generate stochastic resonance (SR) in a biological system. Synthetic bistable systems were chosen because the inducer range in which they exhibit bistability can satisfy one of the three requirements of SR: a weak periodic force is unable to make the transition between states happen. I synthesized several different bistable systems, including toggle switches and self-activators, to select systems matching another requirement: the system has a clear threshold between the two energy states. Their bistability was verified and characterized. At the same time, I attempted to figure out the third requirement for SR – an effective noise serving as the stochastic force – through one of the most widespread toggles, the mutual inhibition toggle, in both yeast and E. coli. A mathematic model for SR was written and adjusted.
Secondly, I began work on designing a new genetic system capable of responding to pulsed magnetic fields. The operators responding to pulsed magnetic stimuli in the rpoH promoter were extracted and reorganized. Different versions of the rpoH promoter were generated and tested, and their varying responsiveness to magnetic fields was recorded. In order to improve efficiency and produce better operators, a directed evolution method was applied with the help of a CRISPR-dCas9 nicking system. The best performing promoters thus far show a five-fold difference in gene expression between trials with and without the magnetic field.
ContributorsHu, Hao (Author) / Wang, Xiao (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2016