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Demand for biosensor research applications is growing steadily. According to a new report by Frost & Sullivan, the biosensor market is expected to reach $14.42 billion by 2016. Clinical diagnostic applications continue to be the largest market for biosensors, and this demand is likely to continue through 2016 and beyond.

Demand for biosensor research applications is growing steadily. According to a new report by Frost & Sullivan, the biosensor market is expected to reach $14.42 billion by 2016. Clinical diagnostic applications continue to be the largest market for biosensors, and this demand is likely to continue through 2016 and beyond. Biosensor technology for use in clinical diagnostics, however, requires translational research that moves bench science and theoretical knowledge toward marketable products. Despite the high volume of academic research to date, only a handful of biomedical devices have become viable commercial applications. Academic research must increase its focus on practical uses for biosensors. This dissertation is an example of this increased focus, and discusses work to advance microfluidic-based protein biosensor technologies for practical use in clinical diagnostics. Four areas of work are discussed: The first involved work to develop reusable/reconfigurable biosensors that are useful in applications like biochemical science and analytical chemistry that require detailed sensor calibration. This work resulted in a prototype sensor and an in-situ electrochemical surface regeneration technique that can be used to produce microfluidic-based reusable biosensors. The second area of work looked at non-specific adsorption (NSA) of biomolecules, which is a persistent challenge in conventional microfluidic biosensors. The results of this work produced design methods that reduce the NSA. The third area of work involved a novel microfluidic sensing platform that was designed to detect target biomarkers using competitive protein adsorption. This technique uses physical adsorption of proteins to a surface rather than complex and time-consuming immobilization procedures. This method enabled us to selectively detect a thyroid cancer biomarker, thyroglobulin, in a controlled-proteins cocktail and a cardiovascular biomarker, fibrinogen, in undiluted human serum. The fourth area of work involved expanding the technique to produce a unique protein identification method; Pattern-recognition. A sample mixture of proteins generates a distinctive composite pattern upon interaction with a sensing platform consisting of multiple surfaces whereby each surface consists of a distinct type of protein pre-adsorbed on the surface. The utility of the "pattern-recognition" sensing mechanism was then verified via recognition of a particular biomarker, C-reactive protein, in the cocktail sample mixture.
ContributorsChoi, Seokheun (Author) / Chae, Junseok (Thesis advisor) / Tao, Nongjian (Committee member) / Yu, Hongyu (Committee member) / Forzani, Erica (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Recent literature indicates potential benefits in microchannel cooling if an inlet orifice is used to suppress pressure oscillations that develop under two-phase conditions. This study investigates the costs and benefits of using an adjustable microchannel inlet orifice. The focus is on orifice effect during steady-state boiling and critical heat flux

Recent literature indicates potential benefits in microchannel cooling if an inlet orifice is used to suppress pressure oscillations that develop under two-phase conditions. This study investigates the costs and benefits of using an adjustable microchannel inlet orifice. The focus is on orifice effect during steady-state boiling and critical heat flux (CHF) in the channels using R134a in a pumped refrigerant loop (PRL). To change orifice size, a dam controlled with a micrometer was placed in front of 31 parallel microchannels. Each channel had a hydraulic diameter of 0.235 mm and a length of 1.33 cm. For steady state two-phase conditions, mass fluxes of 300 kg m-2 s-1 and 600 kg m-2 s-1were investigated. For orifice sizes with a hydraulic diameter to unrestricted hydraulic diameter (Dh:Dh,ur) ratio less than 35 percent, oscillations were reduced and wall temperatures fell up to 1.5 °C. Critical heat flux data were obtained for 7 orifice sizes with mass fluxes from 186 kg m-2 s-1 to 847 kg m-2 s-1. For all mass fluxes and inlet conditions tested, CHF values for a Dh:Dh,ur ratio of 1.8 percent became increasingly lower (up to 37 W cm-2 less) than those obtained with larger orifices. An optimum orifice size with Dh:Dh,ur of 35 percent emerged, offering up to 5 W cm-2 increase in CHF over unrestricted conditions at the highest mass flux tested, 847 kg m-2 s-1. These improvements in cooling ability with inlet orifices in place under both steady-state and impending CHF conditions are modest, leading to the conclusion that inlet orifices are only mildly effective at improving heat transfer coefficients. Stability of the PRL used for experimentation was also studied and improved. A vapor compression cycle's (VCC) proportional, integral, and derivative controller was found to adversely affect stability within the PRL and cause premature CHF. Replacing the VCC with an ice water heat sink maintained steady pumped loop system pressures and mass flow rates. The ice water heat sink was shown to have energy cost savings over the use of a directly coupled VCC for removing heat from the PRL.
ContributorsOdom, Brent A (Author) / Phelan, Patrick E (Thesis advisor) / Herrmann, Marcus (Committee member) / Trimble, Steve (Committee member) / Tasooji, Amaneh (Committee member) / Holcomb, Don (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The world of healthcare can be seen as dynamic, often an area where technology and science meet to consummate a greater good for humanity. This relationship has been working well for the last century as evident by the average life expectancy change. For the greater of the last five decades

The world of healthcare can be seen as dynamic, often an area where technology and science meet to consummate a greater good for humanity. This relationship has been working well for the last century as evident by the average life expectancy change. For the greater of the last five decades the average life expectancy at birth increased globally by almost 20 years. In the United States specifically, life expectancy has grown from 50 years in 1900 to 78 years in 2009. That is a 76% increase in just over a century. As great as this increase sounds for humanity it means there are soon to be real issues in the healthcare world. A larger older population will need more healthcare services but have fewer young professionals to provide those services. Technology and science will need to continue to push the boundaries in order to develop and provide the solutions needed to continue providing the aging world population sufficient healthcare. One solution sure to help provide a brighter future for healthcare is mobile health (m-health). M-health can help provide a means for healthcare professionals to treat more patients with less work expenditure and do so with more personalized healthcare advice which will lead to better treatments. This paper discusses one area of m-health devices specifically; human breath analysis devices. The current laboratory methods of breath analysis and why these methods are not adequate for common healthcare practices will be discussed in more detail. Then more specifically, mobile breath analysis devices are discussed. The topic will encompass the challenges that need to be met in developing such devices, possible solutions to these challenges, two real examples of mobile breath analysis devices and finally possible future directions for m-health technologies.
ContributorsLester, Bryan (Author) / Forzani, Erica (Thesis advisor) / Xian, Xiaojun (Committee member) / Trimble, Steve (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Chimeric antigen receptor (CAR)-T cell therapy is a type of cancer immunotherapy has shown promising results in engineering the T cells which targets a specific antigen. Despite their success rate, there are certain limitations to the use of CAR-T therapies that includes cytokine release syndrome (CRS), neurologic toxicity, lack of

Chimeric antigen receptor (CAR)-T cell therapy is a type of cancer immunotherapy has shown promising results in engineering the T cells which targets a specific antigen. Despite their success rate, there are certain limitations to the use of CAR-T therapies that includes cytokine release syndrome (CRS), neurologic toxicity, lack of response in approximately 50% of treated patients, monitoring of patients treated with CAR-T therapy. However, rapid point- of- care testing helps in quantifying the circulating CAR T cells and can enhance the safety of patients, minimize the cost of CAR-T cell therapy, and ease the management process. Currently, the standard method to quantify CAR-T cell in patient blood samples are flow cytometry and quantitative polymerase chain reaction (qPCR). But these techniques are expensive and are not easily accessible and suitable for point- of- care testing to assist real- time clinical decisions. To overcome these hurdles, here I propose a solution to these problems by rapid optical imaging (ROI)- based principle to monitor and detect CAR-T cells. In this project, a microfluidic device is developed and integrated with two functions: (1) Centrifuge free, filter- based separation of white blood cells and plasma; (2) Optical imaging- based technique for digital counting of CAR T- cells. Here, I carried out proof- of- concept test on the laser cut prototype microfluidic chips as well as the surface chemistry for specific capture of CAR-T cells. These data show that the microfluidic chip can specifically capture CAR-T positive cells with concentration dependent counts of captured cells. Further development of the technology could lead to a new tool to monitor the CAR-T cells and help the clinicians to effectively measure the efficacy of CAR-T therapy treatment in a faster and safer manner.
ContributorsElanghovan, Praveena (Author) / Wang, Shaopeng (Thesis advisor) / Forzani, Erica (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Non-invasive biosensors enable rapid, real-time measurement and quantification of biological processes, such as metabolic state. Currently, the most accurate metabolic sensors are invasive, and significant cost is required, with few exceptions, to achieve similar accuracy using non-invasive methods. This research, conducted within the Biodesign Institute Center for Bioelectronics and Biosensors,

Non-invasive biosensors enable rapid, real-time measurement and quantification of biological processes, such as metabolic state. Currently, the most accurate metabolic sensors are invasive, and significant cost is required, with few exceptions, to achieve similar accuracy using non-invasive methods. This research, conducted within the Biodesign Institute Center for Bioelectronics and Biosensors, leverages the selective reactivity of a chemical sensing solution to develop a sensor which measures acetone in the breath for ketosis and ketoacidosis diagnostics, which is relevant to body weight management and type I diabetes. The sensor displays a gradient of color changes, and the absorbance change is proportional to the acetone concentration in the part- per-million range, making applicable for detection ketosis and ketoacidosis in human breath samples. The colorimetric sensor response can be fitted to a Langmuir-like model for sensor calibration. The sensors best performance comes with turbulent, continuous exposure to the samples, rather than batch sample exposure. With that configuration, these novel sensors offer significant improvements to clinical and at- home measurement of ketosis and ketoacidosis.
ContributorsDenham, Landon (Author) / Forzani, Erica (Thesis advisor) / Wang, Shaopeng (Committee member) / Kulick, Doina (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses on the application of particle image velocimetry (PIV) to the

The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses on the application of particle image velocimetry (PIV) to the study of intracardiac hemodynamics. This is accomplished primarily though the use of ultrasound based PIV, which allows for in vivo visualization of intracardiac flow without the requirement for optical access, as is required with traditional camera-based PIV methods.

The fundamentals of ultrasound PIV are introduced, including experimental methods for its implementation as well as a discussion on estimating and mitigating measurement error. Ultrasound PIV is then compared to optical PIV; this is a highly developed technique with proven accuracy; through rigorous examination it has become the “gold standard” of two-dimensional flow visualization. Results show good agreement between the two methods.

Using a mechanical left heart model, a multi-plane ultrasound PIV technique is introduced and applied to quantify a complex, three-dimensional flow that is analogous to the left intraventricular flow. Changes in ventricular flow dynamics due to the rotational orientation of mechanical heart valves are studied; the results demonstrate the importance of multi-plane imaging techniques when trying to assess the strongly three-dimensional intraventricular flow.

The potential use of ultrasound PIV as an early diagnosis technique is demonstrated through the development of a novel elasticity estimation technique. A finite element analysis routine is couple with an ensemble Kalman filter to allow for the estimation of material elasticity using forcing and displacement data derived from PIV. Results demonstrate that it is possible to estimate elasticity using forcing data derived from a PIV vector field, provided vector density is sufficient.
ContributorsWesterdale, John Curtis (Author) / Adrian, Ronald (Thesis advisor) / Belohlavek, Marek (Committee member) / Squires, Kyle (Committee member) / Trimble, Steve (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Extracellular vesicles (EVs) are membranous particles that are abundantly secreted in the circulation system by most cells and can be found in most biological fluids. Among different EV subtypes, exosomes are small particles (30 – 150 nm) that are generated through the double invagination of the lipid bilayer membrane of

Extracellular vesicles (EVs) are membranous particles that are abundantly secreted in the circulation system by most cells and can be found in most biological fluids. Among different EV subtypes, exosomes are small particles (30 – 150 nm) that are generated through the double invagination of the lipid bilayer membrane of cell. Therefore, they mirror the cell membrane proteins and contain proteins, RNAs, and DNAs that can represent the phenotypic state of their cell of origin, hence considered promising biomarker candidates. Importantly, in most pathological conditions, such as cancer and infection, diseased cells secrete more EVs and the disease associated exosomes have shown great potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring. However, using EVs as diagnostic or prognostic tools in the clinic is hindered by the lack of a rapid, sensitive, purification-free technique for their isolation and characterization. Developing standardized assays that can translate the emerging academic EV biomarker discoveries to clinically relevant procedures is a bottleneck that have slowed down advancements in medical research. Integrating widely known immunoassays with plasmonic sensors has shown the promise to detect minute amounts of antigen present in biological sample, based on changes of ambient optical refractive index, and achieve ultra-sensitivity. Plasmonic sensors take advantage of the enhanced interaction of electromagnetic radiations with electron clouds of plasmonic materials at the dielectric-metal interface in tunable wavelengths.
ContributorsAmrollahi, Pouy (Author) / Wang, Xiao (Thesis advisor) / Forzani, Erica (Committee member) / Hu, Tony Ye (Committee member) / Arizona State University (Publisher)
Created2020
Description
Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing1-3 and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected,4 eliminating transmissions from infection sources is also important to prevent disease

Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing1-3 and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected,4 eliminating transmissions from infection sources is also important to prevent disease transmission. Supportive therapies for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pneumonia such as oxygen supplementation, nebulizers and non-invasive mechanical ventilation all carry an increased risk for viral transmission via aerosol to healthcare workers.5-9 In this work, I study the efficacy of five methods for self-containing aerosols emitted from infected subjects undergoing nebulization therapies with a diverse spectrum on Non-Invasive Positive Pressure Ventilator (NIPPV) with oxygen delivery therapies. The work includes five study cases: Case I: Use of a Full-Face Mask with biofilter in bilevel positive airway pressure device (BiPAP) therapy, Case II: Use of surgical mask in High Flow Nasal Cannula (HFNC) therapy, Case III: Use of a modified silicone disposable mask in a HFNC therapy, Case IV: Use of a modified silicone disposable mask with a regular nebulizer and normal breathing, Case V: Use of a mitigation box with biofilter in a BiPAP. We demonstrate that while cases I, III and IV showed efficacies of 98-100%; cases II and V, which are the most commonly used, resulted with significantly lower efficacies of 10-24% to mitigate the dispersion of nebulization aerosols. Therefore, implementing cases I, III and IV in health care facilities may help battle the contaminations and infections via aerosol transmission during a pandemic.
ContributorsShyamala Pandian, Adithya (Author) / Forzani, Erica (Thesis advisor) / Patel, Bhavesh (Committee member) / Xian, Xiaojun (Committee member) / Arizona State University (Publisher)
Created2021