Matching Items (28)
Description
One out of ten women has a difficult time getting or staying pregnant in the United States. Recent studies have identified aging as one of the key factors attributed to a decline in female reproductive health. Existing fertility diagnostic methods do not allow for the non-invasive monitoring of hormone levels across time. In recent years, olfactory sensing has emerged as a promising diagnostic tool for its potential for real-time, non-invasive monitoring. This technology has been proven promising in the areas of oncology, diabetes, and neurological disorders. Little work, however, has addressed the use of olfactory sensing with respect to female fertility. In this work, we perform a study on ten healthy female subjects to determine the volatile signature in biological samples across 28 days, correlating to fertility hormones. Volatile organic compounds (VOCs) present in the air above the biological sample, or headspace, were collected by solid phase microextraction (SPME), using a 50/30 µm divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) coated fiber. Samples were analyzed, using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). A regression model was used to identify key analytes, corresponding to the fertility hormones estrogen and progesterone. Results indicate shifts in volatile signatures in biological samples across the 28 days, relevant to hormonal changes. Further work includes evaluating metabolic changes in volatile hormone expression as an early indicator of declining fertility, so women may one day be able to monitor their reproductive health in real-time as they age.
ContributorsOng, Stephanie (Author) / Smith, Barbara (Thesis advisor) / Bean, Heather (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2018
Description
Hypoxia is a pathophysiological condition which results from lack of oxygen supply in tumors. The assessment of tumor hypoxia and its response to therapies can provide guidelines for optimization and personalization of therapeutic protocols for better treatment. Previous research has shown the difficulty in measuring hypoxia anatomically due to its heterogenous nature. This makes the study of hypoxia through various imaging modalities and mapping techniques crucial. The potential of hypoxia targeting T1 contrast agent GdDO3NI in generating hypoxia maps has been studied earlier. In this work, the similarities between hypoxia maps generated by MRI using GdDO3NI and pimonidazole based immunohistochemistry (IHC) in non-small cell lung carcinoma bearing mice have been studied. Six NCI-H1975 tumor-bearing mice were studied. All animal studies were approved by Arizona State University’s Institute of Animal Care and Use Committee (IACUC). Post co-injection of GdDO3NI and pimonidazole, T1 weighted 3D gradient echo MR images were acquired. For ex-vivo analysis of hypoxia, 30 μm thick tumor sections were obtained for each harvested tumor and were stained for pimonidazole and counter-stained with DAPI for nuclear staining. Pimonidazole (PIMO) is clinically used as a “gold standard” hypoxia marker. The key process involved stacking and iterative registration based on quality metric SSIM (Structural Similarity) Index of DAPI stained images of 5 consecutive tumor sections to produce a 3D volume stack of 150 μm thickness. Information from the 3D volume is combined to produce one final slide by averaging. The same registration transform was applied to stack the pimonidazole images which were previously thresholded to highlight hypoxic regions. The registered IHC stack was then co-registered with a single thresholded T1 weighted gradient echo MRI slice of the same location (~156 μm thick) using an elastic B-splines transform. The same transform was applied to achieve the co-registration of pimonidazole and MR percentage enhancement image. Image similarity index after the co-registration was found to be greater than 0.5 for 5 of the animals suggesting good correlation. R2 values were calculated for both hypoxic regions as well as tumor boundaries. All the tumors showed a high boundary correlation value of R2 greater than 0.8. Half of the animals showed high R2 values greater than 0.5 for hypoxic fractions. The RMSE values for the co-registration of all the animals were found to be low further suggesting better correspondence and validating the MR based hypoxia imaging.
ContributorsSahu, Sulagna (Author) / Kodibagkar, Vikram D. (Thesis advisor) / Sadleir, Rosalind (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2018
Description
This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids.
Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves.
Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device.
Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves.
Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device.
ContributorsArafa, Hany M (Author) / Blain Christen, Jennifer M (Thesis advisor) / Goryll, Michael (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2018
Description
Severe cases of congenital heart defect (CHD) require surgeries to fix the structural problem, in which artificial grafts are often used. Although outcome of surgeries has improved over the past decades, there remains to be patients who require re-operations due to graft-related complications and the growth of patients which results in a mismatch in size between the patient’s anatomy and the implanted graft. A graft in which cells of the patient could infiltrate, facilitating transformation of the graft to a native-like tissue, and allow the graft to grow with the patient heart would be ideal. Cardiac tissue engineering (CTE) technologies, including extracellular matrix (ECM)-based hydrogels has emerged as a promising approach for the repair of cardiac damage. However, most of the previous studies have mainly focused on treatments for ischemic heart disease and related heart failure in adults, therefore the potential of CTE for CHD treatment is underexplored. In this study, a hybrid hydrogel was developed by combining the ECM derived from cardiac tissue of pediatric CHD patients and gelatin methacrylate (GelMA). In addition, the influence of incorporating gold nanorods (GNRs) within the hybrid hydrogels was studied. The functionalities of the ECM-GelMA-GNR hydrogels as a CTE scaffold were assessed by culturing neonatal rat cardiomyocytes on the hydrogel. After 8 days of cell culture, highly organized sarcomeric alpha-actinin structures and connexin 43 expression were evident in ECM- and GNR-incorporated hydrogels compared to pristine GelMA hydrogel, indicating cell maturation and formation of cardiac tissue. The findings of this study indicate the promising potential of ECM-GelMA-GNR hybrid hydrogels as a CTE approach for CHD treatment.
As another approach to improve CHD treatment, this study sought the possibility of performing a proteomic analysis on cardiac ECM of pediatric CHD patient tissue. As the ECM play important roles in regulating cell signaling, there is an increasing interest in studying the ECM proteome and the influences caused by diseases. Proteomics on ECM is challenging due to the insoluble nature of ECM proteins which makes protein extraction and digestion difficult. In this study, as a first step to perform proteomics, optimization on sample preparation procedure was attempted.
As another approach to improve CHD treatment, this study sought the possibility of performing a proteomic analysis on cardiac ECM of pediatric CHD patient tissue. As the ECM play important roles in regulating cell signaling, there is an increasing interest in studying the ECM proteome and the influences caused by diseases. Proteomics on ECM is challenging due to the insoluble nature of ECM proteins which makes protein extraction and digestion difficult. In this study, as a first step to perform proteomics, optimization on sample preparation procedure was attempted.
ContributorsSugamura, Yuka (Author) / Nikkhah, Mehdi (Thesis advisor) / Smith, Barbara (Committee member) / Willis, Brigham (Committee member) / Arizona State University (Publisher)
Created2018
Description
Connected health is an emerging field of science and medicine that enables the collection and integration of personal biometrics and environment, contributing to more precise and accurate assessment of the person’s state. It has been proven to help to establish wellbeing as well as prevent, diagnose, and determine the prognosis of chronic diseases. The development of sensing devices for connected health is challenging because devices used in the field of medicine need to meet not only selectivity and sensitivity of detection, but also robustness and performance under hash usage conditions, typically by non-experts in analysis. In this work, the properties and fabrication process of sensors built for sensing devices capable of detection of a biomarker as well as pollutant levels in the environment are discussed. These sensing devices have been developed and perfected with the aim of overcoming the aforementioned challenges and contributing to the evolving connected health field. In the first part of this work, a wireless, solid-state, portable, and continuous ammonia (NH3) gas sensing device is introduced. This device determines the concentration of NH3 contained in a biological sample within five seconds and can wirelessly transmit data to other Bluetooth enabled devices. In this second part of the work, the use of a thermal-based flow meter to assess exhalation rate is evaluated. For this purpose, a mobile device named here mobile indirect calorimeter (MIC) was designed and used to measure resting metabolic rate (RMR) from subjects, which relies on the measure of O2 consumption rate (VO2) and CO2 generation rate (VCO2), and compared to a practical reference method in hospital. In the third part of the work, the sensing selectivity, stability and sensitivity of an aged molecularly imprinted polymer (MIP) selective to the adsorption of hydrocarbons were studied. The optimized material was integrated in tuning fork sensors to detect environmental hydrocarbons, and demonstrated the needed stability for field testing. Finally, the hydrocarbon sensing device was used in conjunction with a MIC to explore potential connections between hydrocarbon exposure level and resting metabolic rate of individuals. Both the hydrocarbon sensing device and the metabolic rate device were under field testing. The correlation between the hydrocarbons and the resting metabolic rate were investigated.
ContributorsLiu, Naiyuan (Author) / Forzani, Erica (Thesis advisor) / Raupp, Gregory (Committee member) / Holloway, Julianne (Committee member) / Thomas, Marylaura (Committee member) / Westerhoff, Paul (Committee member) / Arizona State University (Publisher)
Created2018
Description
Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac tissue constructs have suffered from electrically insulated matrices and low cell retention. To address these drawbacks, we fabricated micropatterned hybrid hydrogel constructs (uniaxial microgrooves with 50 µm with) using a photocrosslinkable gelatin methacrylate (GelMA) hydrogel incorporated with gold nanorods (GNRs). The electrical impedance results revealed a lower impedance in the GelMA-GNR constructs versus the pure GelMA constructs. Superior electrical conductivity of GelMA-GNR hydrogels (due to incorporation of GNRs) enabled the hybrid tissue constructs to be externally stimulated using a pulse generator. Furthermore, GelMA-GNR tissue hydrogels were tested to investigate the biological characteristics of cultured cardiomyocytes. The F-actin fiber analysis results (area coverage and alignment indices) revealed higher directed (uniaxial) cytoskeleton organization of cardiac cells cultured on the GelMA-GNR hydrogel constructs in comparison to pure GelMA. Considerable increase in the coverage area of cardiac-specific markers (sarcomeric α-actinin and connexin 43) were observed on the GelMA-GNR hybrid constructs compared to pure GelMA hydrogels. Despite substantial dissimilarities in cell organization, both pure GelMA and hybrid GelMA-GNR hydrogel constructs provided a suitable microenvironment for synchronous beating of cardiomyocytes.
ContributorsMoore, Nathan Allen (Author) / Nikkhah, Mehdi (Thesis director) / Smith, Barbara (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Statistical process control (SPC) is an important quality application that is used throughout industry and is composed of control charts. Most often, it is applied in the final stages of product manufacturing. However it would be beneficial to apply SPC throughout all stages of the manufacturing process such as the beginning stages. This report explores the fundamentals of SPC, applicable programs, important aspects of implementation, and specific examples of where SPC was beneficial. Important programs for SPC are general statistical software such as JMP and Minitab, and some programs are made specifically for SPC such as SPACE: statistical process and control environment. Advanced programs like SPACE are beneficial because they can easily assist with creating control charts and setting up rules, alarms and notifications, and reaction mechanisms. After the charts are set up it is important to apply rules to the charts to see when a system is running off target which indicates the need to troubleshoot and investigate. This makes the notification part an integral aspect as well because attention and awareness must be brought to out of control situations. The next important aspect is ensuring there is a reaction mechanism or plan on what to do in the event of an out of control situation and what to do to get the system running back on target. Setting up an SPC system takes time and practice and requires a lot of collaboration with experts who know more about the system or the quality side. Some of the more difficult parts of implementation is getting everyone on board and creating trainings and getting the appropriate personnel trained.
ContributorsSennavongsa, Christy (Author) / Raupp, Gregory (Thesis director) / Dai, Lenore (Committee member) / Materials Science and Engineering Program (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Growing interest in using volatile organic compounds (VOCs) as markers of biological function and health has highlighted the need for a standardized method to analyze gas metabolites released by biological organisms. Non-destructive VOC collection techniques have emerged, allowing researchers to study diseases over time without compromising the sample. However, continuous sampling is often not performed, and previous systems have not undergone rigorous testing. To overcome current limitations, we developed a gas flow-based device and tested it for consistent headspace sweeping, cell viability and morphology, and detection accuracy. The results showed that the device offers a high degree of reproducibility, and our modeling shows that laminar flow conditions are maintained at experimental gas flow rates, ensuring consistent headspace sweeping. Furthermore, our modular design allowed us to adjust the temperature and input gas, allowing us to maintain a favorable environment for cell culture. Isotopic labeling and heavy VOC production confirmed that the system achieves sufficient sensitivity and reproducibility to monitor metabolic changes across time. This comprehensive evaluation demonstrates that our flow-based device has great potential in further research and subsequent clinical applications.
ContributorsAmbrose, Benjamin (Author) / Smith, Barbara (Thesis director) / Eshima, Jarrett (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor)
Created2023-05
Description
Advancing the understanding and treatment of many neurological disorders can be achieved by improving methods of neuronal detection at increased depth in the mammalian brain. Different cell subtypes cannot be detected using non-invasive techniques beyond 1 mm from cortical surface, in the context of targeting particular cell types in vivo (Wang, 2012). These limitations in the depth of imaging and targeting are due to optical scattering (Ntziachristos, 2010). In order to overcome these restrictions, longer wavelength fluorescent proteins have been utilized by researchers to see tagged cells at depth. Optical techniques such as two-photon and confocal microscopy have been used in combination with fluorescent proteins to expand depth, but are still limited by the penetration depth of light due to optical scattering (Lee, 2015). This research aims to build on other detection methods, such as the photoacoustic effect and automated fluorescence-guided electrophysiology, to overcome this limitation.
ContributorsAridi, Christina (Author) / Smith, Barbara (Thesis director) / Marschall, Ethan (Committee member) / Barrett, The Honors College (Contributor) / Watts College of Public Service & Community Solut (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
Description
Portable health diagnostic systems seek to perform medical grade diagnostics in non-ideal environments. This work details a robust fault tolerant portable health diagnostic design implemented in hardware, firmware and software for the detectionof HPV in low-income countries. The device under device under test (DUT) is a fluorescence based lateral flow assay (LFA) point-of-care (POC) device. This work’s contributions are: firmware and software development, calibration routine implementation, device performance characterization and a proposed method of in-software fault detection. Firmware was refactored from the original implementation of the POC fluorescence reader to expose an application programming interface (API) via USB. Companion software available for desktop environments (Windows, Mac and Linux) was created to interface with this firmware API and conduct macro level routines to request and receive fluorescence data while presenting a user-friendly interface to clinical technicians. Lastly, an environmental chamber was constructed to conduct sequential diagnostic reads in order to observe sensor drift and other deviations that might present themselves in real-world usage. The results from these evaluations show a standard deviation of less than 1% in fluorescence readings in nominal temperature environments (approx. 25C) suggesting that this system will have a favorable signal-to-noise (SNR) ratio in such a setting. In non-ideal over heated environments (≥38C), the evaluation results showed performance degradation with standard deviations as large as 15%.
ContributorsLue Sang, Christopher David (Author) / Blain Christen, Jennifer M (Thesis advisor) / Ozev, Sule (Committee member) / Goryll, Michael (Committee member) / Raupp, Gregory (Committee member) / Arizona State University (Publisher)
Created2022