PhD, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

The full impact of personalized medicine can only be realized through on-demand and convenient access to individual biomarker data both at home and in the clinic. Biosensors that enable on-demand quantification of drugs, hormones, and other clinically relevant analytes have long been promised as the next breakthrough for facilitating precision medicine. While point-of-care and continuous glucose monitors have drastically improved outcomes and quality of life for diabetic patients, there has been virtually no clinical adoption of biosensors for other target analytes beyond glucose. This is unfortunate, as there are numerous other opportunities where the potential for improved patient outcomes through on-demand access to patient-specific biomarker data is well-documented, such as in the precision dosing of narrow therapeutic index drugs (e.g., warfarin, digoxin, cyclosporine), patients requiring postoperative monitoring (e.g., troponin, cystatin C, anticoagulation status), and in tracking longitudinal changes of biomarkers indicative of disease progression (e.g., NT-proBNP, PSA). The technology behind glucose monitoring, i.e., enzymatic biosensing, is unfortunately not generalizable as it is limited to high concentration analytes (~mM) and requires a readily available enzyme that can oxidize/reduce analytes of interest. Beyond enzymatic glucose sensors, electrochemical aptamer sensors comprise the only other biosensing modality that has been broadly validated in vivo. Despite demonstration of continuous sensing for over a dozen different analytes in animal models, no electrochemical aptamer sensor has seen commercial viability due to lack of integration into feasibly deployable devices. Thus, described herein are several key advancements in translating electrochemical aptamer sensors into point-of-care and wearable devices as enabled by the fundamental insights and innovations put forth through this work. Specifically, we demonstrate sensors integrated into feasibly d (open full item for complete abstract)

Committee: Jason Heikenfeld Ph.D. (Committee Chair); Stacey Schutte Ph.D. (Committee Member); Jack Rubinstein M.D. (Committee Member); Alexander Vinks Pharm.D. Ph.D. (Committee Member); Leyla Esfandiari Ph.D. (Committee Member) Subjects: Biomedical Research

PhD, University of Cincinnati, 2023, Engineering and Applied Science: Electrical Engineering

A novel approach to detect unbound cortisol in saliva, a key biomarker for common mental disorders, has been developed in this study. This method employs a polymer lab-on-a-chip (LOC) based on microfluidic capillary flow assay (MCFA) with on-chip dried reagents, and a portable fluorescence analyzer for rapid and accurate quantification. The detection of unbound cortisol in saliva has emerged as an effective biochemical technique for assessing conditions such as stress, depression, and anxiety, which afflict over 400 million individuals worldwide. Cortisol, often referred to as the stress hormone, is produced in the human adrenal cortex and plays a vital role in regulating the body's response to stress. Chronic stress can lead to disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol dysfunction, inflammation, and pain. Unlike cortisol levels in blood, cortisol levels in saliva directly reflect the amount of unbound or bioavailable hormones, making them a valuable indicator of mental health. Continuous and rapid monitoring of salivary cortisol levels holds great promise for diagnosing common mental disorders. To facilitate the reliable measurement of cortisol in saliva, a one-step rapid diagnostic device was developed. This device enables highly sensitive quantitative detection of cortisol and is complemented by a portable fluorescence analyzer. This analyzer was designed to measure the optical signal emitted from the MCFA device, converting it into biomarker concentration. The portable analyzer operates using transmission-based fluorescence measurements, with the MCFA device enclosed in a cartridge placed between the excitation LED source and the detecting Photodiodes, ensuring accurate readings. The custom-built portable analyzer incorporates an Intel compute stick, touch screen, and power source, providing up to 10 hours of in-field testing capability. The integrated system's functionality was validated using cort (open full item for complete abstract)

Committee: Chong Ahn Ph.D. (Committee Chair); Leyla Esfandiari Ph.D. (Committee Member); Tao Li Ph.D. (Committee Member); Bon Ku Ph.D. (Committee Member); Rashmi Jha Ph.D. (Committee Member) Subjects: Immunology

Doctor of Philosophy, The Ohio State University, 2023, Materials Science and Engineering

The work in this dissertation is focused on the development of new manufacturing technologies at the early stage. Two concepts are developed in the category of Impact Welding and two in the category of Metamorphic Manufacturing. Under the Impact Welding category two different welding processes are studied, the Vaporizing Foil Actuator Welding and the Augmented Laser Impact Welding processes. Both of these processes were demonstrated to produce impact welds between traditionally unweldable aircraft aluminum alloys which performed as well or better than comparable riveted joints without the need for the drilling of holes or removal of surface coatings. Additionally, basic engineering guidelines are established for the design of foils for the Vaporizing Foil Actuator Welding process and basic performance metrics are established for the Augmented Laser Impact Welding technique. Two new data analysis techniques were developed for the Augmented Laser Impact Welding process which were validated by the use of high-speed videography. Models of the impact conditions for both of these impact welding techniques were established. For the Augmented Laser Impact Welding process, a technique for accurately measuring the welding velocity during an impact event is developed and validated. Metamorphic Manufacturing refers to the agile use of deformation to create shapes and modify microstructure. In this area two concepts were developed where metallic components are transformed from one shape into a second more desirable and useful form. A device and process for bending medical fixation plates to match patient skeletal anatomy is developed. The method can make arbitrary controlled shapes and may save time in the operating room for reconstruction surgeries. The second concept is an approach for Robotic Blacksmithing, a process for incrementally transforming a malleable material into useful shapes by deformation. This concept was initially developed on a purpose-built desktop robotic (open full item for complete abstract)

Committee: Glenn Daehn (Advisor); Antonio Ramirez (Committee Member); Boyd Panton (Committee Member); Enam Chowdhury (Committee Member) Subjects: Materials Science; Medicine; Robotics

Doctor of Philosophy (Ph.D.), University of Dayton, 2023, Electrical Engineering

The recent pandemic of Corona-virus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed an urgent need to rapidly and accurately identify the genetic material of SARS-CoV-2, an enveloped ribonucleic acid (RNA) virus, in upper respiratory specimens from people. Further, foodborne and waterborne diseases are not only spreading faster, but also appear to be emerging more rapidly than ever before and are able to circumvent conventional control measures. The Polymerase Chain Reaction (PCR) system is a well-known diagnostic tool for many applications in medical diagnostics, environmental monitoring, and food and water quality assessment. Here, we describe the design, development, and testing of a portable, low-cost, and real-time PCR system that can be used in emergency health crises and resource-poor situations. The described PCR system incorporates real-time reaction monitoring using fluorescence as an alternative to gel electrophoresis for reaction analysis, further decreasing the need of multiple reagents, reducing sample testing cost, and reducing sample analysis time. The bill of materials cost of the described system is approximately $340. The described PCR system utilizes a novel progressive selective proportional–integral–derivative controller that helps in reducing sample analysis time. In addition, the system employs a novel primer-based approach to quantify the initial target amplicon concentration, making it well-suited for food and water quality assessment. The developed PCR system performed DNA amplification at a level and speed comparable to larger and more expensive commercial table-top systems. The fluorescence detection sensitivity was also tested to be at the same level as commercially available multi-mode optical readers, thus making the PCR system an attractive solution for medical point-of-care and food and water quality assessment. In general, sensitive testing methods require genetic material (open full item for complete abstract)

Committee: Vamsy Chodavarapu P.E., Ph.D. (Committee Chair); Amy Neidhard-Doll P.E., Ph.D. (Committee Member); Guru Subramanyam Ph.D. (Committee Member); Yvonne Sun Ph.D. (Advisor) Subjects: Biomedical Engineering; Electrical Engineering

Doctor of Philosophy, The Ohio State University, 2021, Chemistry

Mass spectrometry (MS) is a powerful analytical tool that plays crucial roles in many fields, including disease diagnosis, environmental monitoring, drug discovery, and chemical reaction screening and their mechanistic studies. The plethora of applications using MS continue to expand; this, in turn, has enabled continuous explorations that have resulted in the development of innovative ion sources and analyzers. Ambient ionization is a recent innovation that enables direct in-situ complex mixture analysis without having lengthy pretreatment of the sample (e.g., extraction, precipitation, lyophilization). Therefore, direct analysis using ambient ionization reduces analysis time and allows high throughput chemical detection. With such developments in ionization techniques, chemical instrumentation is getting advanced into new applications which were not previously possible. A future outlook on instrumentation is manufacturing portable mass spectrometers. In addition to basic figures of merits of the mass spectrometer, portable mass spectrometer broadens the scope of modern MS due to less power consumption, relatively low cost, and fieldable application. This dissertation describes the development of MS-based applications for clinical diagnosis utilizing ambient ionization and portable mass spectrometer (Chapters 2-4) and reaction screening (Chapter 5). Chapters 2-4 describe the innovations of coupling microfluidic paper-based analytical device (µPAD) to the portable mass spectrometer for ultrasensitive malaria diagnostic. Diagnosis of malaria, which is one of the deadliest infectious diseases, is the primary focus of this dissertation. This disease is encountered in developing countries and other resource-limited settings. Thus, the objective is positioned toward developing an ultrasensitive point-of-care tool so that all people can have equal opportunity to get diagnosed early and accurately. In chapter 2, the use of a portable mass spectrometer became the focus of t (open full item for complete abstract)

Committee: Abraham Badu-Tawiah (Advisor); Robert Baker (Committee Member); Vicki Wysocki (Committee Member) Subjects: Analytical Chemistry

MS, University of Cincinnati, 2021, Engineering and Applied Science: Chemical Engineering

The novel Coronavirus Disease has affected the lives of millions of people all around the world, thus acquiring the need for rapid testing. Point-of-care (POC) diagnostics are such rapid tests that are used to diagnose an infectious disease, and provide the results within minutes of the test being done, thereby allowing rapid treatment. Paper-based point-of-care devices have become very popular due to their portability, low-cost and ease of fabrication and distribution. This project describes a simple and inexpensive paper-based modular system for detecting the presence/absence of DNA/RNA targets using a smartphone. Smartphones have an extremely sophisticated hardware and software package in a truly portable, user-friendly and inexpensive manner [5]. Therefore, it has played a major role in the point-of- care diagnostic field as standalone biosensing systems for medical applications [5]. They are replacing laboratory analytical and biomedical equipment. The following is a smartphone enabled nucleic acid based amplification device. Molecular based testing depends on the amplification of the target pathogen DNA/RNA. Current molecular diagnostic systems rely on Polymerase Chain Reaction (PCR) to selectively find, amplify and detect target pathogen DNA/RNA in human samples. As an alternate to PCR, Loop Mediated Isothermal Amplification (LAMP) reaction can amplify a known DNA/RNA sequence in the target pathogen without the use of bulky, power-consuming thermocyclers. Liquid aliquots can be hard to deal with and have supply chain issues, especially during a pandemic. Transportation of paper substrates is easier as all the LAMP reagents are present in the dried format on it. Paper based detection is more suitable for POC diagnostics. Paper-based LAMP platform involves a paper substrate on which the DNA/RNA amplification reaction takes place. The first aim talks about characterizing visual detection systems for detecting amplified LAMP products. This involves exploring the (open full item for complete abstract)

Committee: Aashish Priye Ph.D. (Committee Chair); Greg Harris Ph.D. (Committee Member); Surya Prasath Ph.D. (Committee Member) Subjects: Molecular Biology

DNP, Kent State University, 2021, College of Nursing

The use of point-of-care ultrasound with a handheld device in the COVID-19 pandemic has several advantages over other imaging modalities. Furthermore, having nurse practitioners who also complete the physical assessment complete point-of-care ultrasound with the handheld device cuts down on the number of providers entering the room. This research project is a single-sample, prospective, cohort design comparing ultrasound findings and diagnoses made by nurse practitioners using point-of-care ultrasound with a handheld device to those made by physicians viewing the same images. Nurse practitioners obtained point-of-care ultrasound images using a handheld device on patients with COVID-19. The images were sent to the physician using the project site email without any patient identification on the images. Physicians independently filled out the same checklist of findings from the ultrasound images and made an independent diagnosis. Concordance between nurse practitioner and physician interpretation of thoracic point-of-care ultrasound images using the handheld device was examined using the Cohen Kappa index. Power analysis was performed using function kappaSize::PowerBinary, finding a minimum population size of 110 needed for a null Cohen kappa value of .62 and an alternative Kappa value of .81. The primary goal of the project was met with a final Cohen kappa of 0.81. Over a three-month period, 98 different patients received POCUS exams with HHU, with a total of 110 exams completed. The Cohen's kappa was 0.81, which represents strong agreement (McHugh, 2012). Implications for the project are adding to the evidence that nurse practitioners are capable of using point-of-care ultrasound and credentialing for nurse practitioners in ultrasound at the project site.

Committee: Lisa Onesko (Committee Chair); Louise Knox (Committee Member); Amy Petrinec (Committee Member) Subjects: Nursing

MS, University of Cincinnati, 2021, Engineering and Applied Science: Electrical Engineering

In this work, a whole blood /plasma separation lab chip using hetero-packed colloidal beads or membrane filters has been designed, developed, characterized and compared for the applications of point-of-care test (POCT) clinical diagnostics. For the whole blood/plasma separation lab chip with hetero-packed beads, the colloidal beads have been packed in multilayers from the bottom with larger sizes to the top with small sizes of colloidal beads to improve separation capability. The smallest beads are packed on the top layer which provide good separation function while preventing the leak of blood cells, so the plasma can be successfully separated from the whole blood by capillary force. The larger beads on the bottom of the separation chamber support the upper layers with smaller beads. The separated plasma can be pulled by the capillary force which is generated by the larger pores on the bottom layers. Then, the separated plasma flows continuously through the microchannel which has sensing or control channels for the target assays. With a whole blood sample of 8 ul, around 1 ul of plasma (plasma recovery 20.8 %) has been separated from the separation lab chip developed with hetero-packed colloidal beads. The blood/plasma separation lab chips with hetero-packed colloidal bead have produced enough plasma to perform immunoassays for point-of-care test (POCT) lab chips. For the whole blood/plasma separator with membrane filters, a blood/plasma separation lab chip with membrane filter has been developed and characterized as a well-established standard vehicle, where the membrane filter is placed on the top of the sample chamber and encapsulated between two polymer chip layers as an embedded filter. The membrane filter has a structure with various sizes of pores, so the most blood cells can be captured in the smaller pores without lysis while the plasma can flow through the larger pores and then deliver to the sensing channels by capillary force. The blood/plasma separa (open full item for complete abstract)

Committee: Chong Ahn Ph.D. (Committee Chair); Leyla Esfandiari Ph.D. (Committee Member); Tao Li Ph.D. (Committee Member) Subjects: Electrical Engineering

PhD, University of Cincinnati, 2020, Arts and Sciences: Physics

Stress is often called “the silent killer” due to its hidden effects on everything from heart disease to psychological health. Therefore, having a stress-monitoring system would be beneficial for the self-management of mental and physical health of individuals within the stressful environment of today's world. In this work, we introduce an improved method for developing a robust and user-friendly point of care (POC) diagnostic device to monitor stress and depression biomarkers (cortisol and dopamine) in non-invasive biofluids (sweat, urine, saliva). Paper-based microfluidics represents a desirable substrate for low cost, easy to store/transport/use diagnostic devices that can be used to analyze bodily fluids (such as blood, sweat or urine) for a variety of conditions. The principle of capillary flow in paper-based microfluidics makes the small sample volume move by capillary action without the need for external pumps and are capable of performing multiple assays simultaneously on a single device. Most POC biomarker monitoring tests are based on immunochemical reactions using antibody recognition. The use of aptamer- functionalized gold nanoparticles as a colorimetric method of detection in strip biosensors is an attractive alternative to overcome the limitations of current methods: immunogenicity, sophisticated laboratory techniques, and time-consuming. A paper-based apata-sensor device is designed to detect the levels of stress biomarkers within 10-15 minutes by providing a red band in the test zone of the biosensor. The color intensity in the test zone of the device indicates the target concentration in the sample. The aptamer-based biosensor for the cortisol detection in sweat successfully exhibited a visual limit of detection of 1 ng/mL under optimized condition, readily covering the normal range of free cortisol in sweat (8–140 ng/mL). No significant cross-reactivity to other stress biomarkers was observed. The detection of dopamine in urine has been invest (open full item for complete abstract)

Committee: Andrew Steckl Ph.D. (Committee Chair); Hans Peter Wagner Ph.D. (Committee Chair); Leyla Esfandiari Ph.D. (Committee Member); Kay Kinoshita Ph.D. (Committee Member) Subjects: Physics

PhD, University of Cincinnati, 2020, Arts and Sciences: Chemistry

Noble metal nanoparticles have been used as sensors utilizing the phenomenon localized surface plasmon resonance (LSPR). LSPR based sensors are competitive because of the high sensitivity and can be made label-free. LSPR sensors have great potential as diagnostic tools for point-of-care and in-field scenarios. In this work, I have developed three unique sensors that utilizes LSPR. First, a nanoparticle-based localized surface plasmon resonance (LSPR) assay to detect copper ions in biological samples in vitro was developed. After reducing the cellular Cu2+ ions to Cu+ ions using ascorbic acid, a `click' reaction is carried out to covalently couple a dye to the surface of a gold nanoparticle array. Then utilizing the ability to fabricate LSPR arrays on substrates we developed durable flexible nanoparticle substrates for point-of-care sensing. Second, I developed a rapid, LSPR based diagnostic test for chlamydia without the need for amplification. This technique can be developed into a strip and be used for other STIs in a multiplexed manner. Last, a flexible plastic, sensitive sensor for cortisol and neuropeptide y was developed. These sensors show low limits of detection, good reproducibility, and good selectivity in complex biological samples. Moreover, they all show excellent promise as point-of-care sensors which can greatly expand medical diagnostics for at-home and in the field use.

Committee: Laura Sagle Ph.D. (Committee Chair); Peng Zhang Ph.D. (Committee Chair); In-Kwon Kim Ph.D. (Committee Member); Pearl Tsang Ph.D. (Committee Member) Subjects: Analytical Chemistry

PhD, University of Cincinnati, 2020, Engineering and Applied Science: Electrical Engineering

The objective of this research work is to develop a functional lab-on-chip (LOC) and a smartphone compatible point-of-care-testing (POCT) platform to quantitatively determine the concentration of a target biomarker in biological fluids for disease diagnostics in resource-limited environment. Majority of deaths related to infectious diseases occur in resource-poor countries having limited access to clinical laboratory facilities and trained personnel. Developing reliable diagnostic tests to be used at the point-of-care can result in earlier disease diagnosis, improved patient treatment, and more efficient outbreak prevention. The realization of an ideal POCT system largely relies on the development of cheap and disposable micro?uidic devices that can be easily integrated to low power electronics with a user-friendly interface.In this research, for the first time, a new microchannel capillary flow assay (MCFA) LOC for high-sensitive chemiluminescence ELISA using on-chip reagent lyophilization has been developed and applied for the detection of malarial biomarker Plasmodium Falciparum Histidine Rich Protein 2 (PfHRP2). This work also reports the design and development of a smartphone based POCT analyzer for detecting chemiluminescent signals from preloaded MCFA LOC. MCFA LOCs were designed for single-step sample loading and capillary liquid transport to initiate chemiluminescence sandwich ELISA in the reaction chambers. A methodology towards lyophilization of chemiluminescent substrate while restoring the substrate functionality in artificial serum was successfully established which paves the way towards developing a sample-to-answer type POCT platform . On sample addition, the functionally designed microchannels with adequately hydrophilic surfaces pull the sample towards the dried reagents and reconstitutes them.The designed microfluidic chip controls sequential arrival of reconstituted reagents in the reaction chamber producing the desired chemil (open full item for complete abstract)

Committee: Chong Ahn Ph.D. (Committee Chair); Marc Cahay Ph.D. (Committee Member); Leyla Esfandiari Ph.D. (Committee Member); Jungyoup Han Ph.D. PMP (Committee Member); Rashmi Jha Ph.D. (Committee Member) Subjects: Electrical Engineering

Doctor of Philosophy, Case Western Reserve University, 2020, EECS - Electrical Engineering

This project has developed a microfluidic sensor for comprehensive assessment of human whole blood hemostasis using miniaturized broadband dielectric spectroscopy. In particular, first, a Gen-1 microfluidic sensor for dielectric coagulometry, termed ClotChip, has been developed. The sensor employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Using an impedance analyzer, the sensor is shown to measure the real part of complex relative dielectric permittivity of human whole blood in a frequency range of 10kHz to 100MHz using <10 μL of it. The temporal variation of dielectric permittivity at 1MHz is taken as the ClotChip readout featuring a time to reach a permittivity peak parameter, Tpeak, which corresponds to the onset of CaCl2-initiated coagulation of the blood sample. Next, a biocompatible version of the sensor (Gen-2), fabricated entirely out of PMMA, has been developed. The readout of the Gen-2 sensor features a time to reach a permittivity peak, Tpeak, as well as a maximum change in permittivity after the peak, Δεr,max, as two distinct parameters of the sensor readout that are respectively sensitive towards detecting non-cellular (i.e., coagulation factor) and cellular (i.e., platelet) abnormalities in the hemostatic process. The sensor performance has been benchmarked against standard coagulation assays like rotational thromboelastometry (ROTEM) and Light Transmission Aggregometry (LTA) to evaluate the utility of its readout parameters in capturing the clotting dynamics using ex vivo modified blood samples. Tpeak exhibited very strong positive correlations with the ROTEM clotting time (CT) parameter, whereas Δεr,max exhibited strong positive correlation both with the ROTEM maximum clot firmness (MCF) parameter and the LTA. Finally, clinical studies with blood samples from patients suffering from a variety of coagulation defects, on factor replacement therapy and on d (open full item for complete abstract)

Committee: Pedram Mohseni (Advisor); Anirban Sen Gupta (Committee Member); Umut Gurkan (Committee Member); Philip Feng (Committee Member); Michael Suster (Committee Member) Subjects: Biomedical Engineering; Electrical Engineering; Engineering

Doctor of Philosophy, University of Toledo, 2019, Biomedical Engineering

The development of detection methods for the novel biomarkers can have a significant impact on the research and clinical applications such as drug discovery, disease diagnosis, and treatment monitoring. Histatin 3 (H3) is an antimicrobial salivary peptide that possesses the capability of being a therapeutic agent against oral candidiasis and has recently been linked to acute stress as a potential novel biomarker. Stress biomarkers reflect the physical and cognitive performance of an individual, and their monitoring in real-time is of vital importance for the high-risk jobs, including military, pilot, and surgeon, where higher vigilance is required for an extended period. The salivary levels of H3 also have been correlated with the HIV-infection and associated oral candidiasis. Therefore, monitoring H3 levels in human saliva can provide essential information about an individual's health status, including HIV-infection, oral candidiasis, and acute stress. Additionally, H3 detection could serve as therapeutic drug monitoring if H3 can be established as an alternative therapeutic agent. The currently available detection techniques for H3 are gel chromatography, high-performance liquid chromatography (HPLC), mass spectrometry (MS), and antibody-based immunoassays. The Chromatographic and mass-spectroscopic methods are laborious, utilize expensive instrumentation, require trained personnel, and time-consuming. Whereas antibody-based immunoassays are not widely validated, expensive, sensitive to temperature, and have a short lifespan. This void in analytical methods is not just for H3 but also applies to several other biomarkers in saliva. Even though saliva is considered as an optimal biofluid, several limitations are impeding its use in diagnostic and research. The major hurdles include the deficient concentration of biomarkers, need of laboratory-based preprocessing to remove mucin and interfering particulate matters, and lack of standard sample collection methods. A (open full item for complete abstract)

Committee: Cameron Brent PhD (Advisor); Giovannucci David PhD (Committee Member); Kim Dong-Shik PhD (Committee Member); Pappada Scott PhD (Committee Member); Pirnstill Casey PhD (Committee Member) Subjects: Analytical Chemistry; Biochemistry; Biomedical Engineering; Biomedical Research; Chemical Engineering; Chemistry; Health Care; Health Sciences; Molecular Biology; Nanotechnology

PhD, University of Cincinnati, 2019, Arts and Sciences: Chemistry

This thesis contains work that has been done in order to improve the sensitivity and selectivity of localized surface plasmon resonance sensors, specifically in regards to medical and point-of-care diagnostics. For centuries the vivid optical properties of gold nanoparticles have captured the attention of both artists and scientists. Today, due to the bold colorimetric properties that are highly tunable, plasmonic nanoparticles have been key to their widespread popularity and incorporation into medical diagnostics. As diagnostics become more readily available for self-monitoring of human health, it is imperative that new devices are produced that are highly accurate, precise, and affordable for consumer use. Applying the colorimetric properties of plasmonic nanoparticles, their colorimetric readout helps create a response that is either a simple yes or no, or a quantitative colorimetric readout. The contents of this thesis highlight efforts to enhance the surface chemistry to improve the sensitivity of nanoparticle substrates for improved detection of health relevant biomolecules. In addition, integration of these nanoparticles into extracellular matrix and lipid membrane systems help improve the selectivity of these model schemes. These strategies applied in this thesis are aimed toward improving medical diagnostics to make them affordable for point-of-care scenarios to improve the quality of human health.

Committee: Laura Sagle Ph.D. (Committee Chair); Ruxandra Dima Ph.D. (Committee Member); Patrick Limbach Ph.D. (Committee Member) Subjects: Chemistry

PhD, University of Cincinnati, 2018, Engineering and Applied Science: Electrical Engineering

Stress manifests itself in human body through various psycho social, physical, chemical formats. Its integrated effect on human health is detrimental, vital symptoms are depression, neurological disorder, cardio thoracic disease, weight loss or gain, high blood sugar. Primary elements that enable better understanding of stress are several “biomarkers” (hormones and neurotransmitters) present in body fluids. Concentrations of these biomarkers accurately predict the physical and mental state of the individual. Key biomarkers associated with stress and the focus of this research are cortisol, serotonin, dopamine, norepinephrine, epinephrine, neuropeptide Y (NPY), brain-derived neurotropic factor (BDNF). Human bio fluids are a trove of information regarding these biomarkers. Elevated levels of hormones released into the blood stream also diffuse into other body fluids such as sweat, interstitial fluid, saliva, urine. Identification and measurement of concentration of these markers provide a direct pathway for stress assessment. Overall objective of this thesis is to provide its readers with a unified platform of information which can be used to understand physiological effect of these biomarkers and give an insight into various techniques that can be used to develop a smart detection system for these markers. For this research, primary focus has been given to UV-Vis spectroscopy as the detection technique. UV spectroscopy of stress biomarkers performed in the range of 190 – 400 nm reveals presence of primary, secondary, tertiary absorption peaks at near UV wavelengths. Cortisol, lipophilic glucocorticoid hormone (MW: 362 Da) has unique absorption peak at ?max: 247 nm. UV absorption profile of serotonin (MW: 175Da) show four absorption peaks (?1: 201, ?2: 224, ?3: 278 and ?4:298 nm). Amine group of biomarkers collectively termed as Catechols - Dopamine (MW 153 Da), Norepinephrine (MW: 169 Da) and Epinephrine (MW: 183 Da) displays characteristic absorption peaks at ?1: 20 (open full item for complete abstract)

Committee: Andrew Steckl Ph.D. (Committee Chair); Je-Hyeong| Bahk Ph.D. (Committee Member); James Herman Ph.D. (Committee Member); Rashmi Jha Ph.D. (Committee Member); Richard Murdock Ph.D. (Committee Member) Subjects: Engineering

PhD, University of Cincinnati, 2018, Engineering and Applied Science: Electrical Engineering

A simple and low-cost approach to evaluate blood coagulation ability using the paper-based no-reaction lateral flow assay (nrLFA) device for point-of-care diagnostics was investigated. The nrLFA device consists of sample pad, analytical membrane and wicking pad. In the first part of the study, flow properties of various analytical membranes (nitrocellulose, nylon, PVDF, etc.) as well as reproducibility of the nrLFA device were investigated. Effect of sample volume and blood hematocrit (Hct) on fluid transport in the nrLFA device were also studied. In the second part of the study, decreased travel distance of red blood cells (RBCs) on the nrLFA at a fixed time was observed when using whole blood with increased coagulation ability, and the nrLFA device exhibited larger detection range and better linearity than a clinical instrument in coagulation measurement. Thus, it was concluded that the nrLFA device could be potentially utilized in blood coagulation monitoring. In the third part of the study, a clinical trial using the nrLFA device in coagulation monitoring for patients taking warfarin (anticoagulant) was conducted, and the nrLFA device was capable to statistically distinguish the blood coagulation between healthy volunteers and patients with INR equal to or greater than 2.6. In the forth part of the study, a calibration method was developed to correct the effect of Hct and yet preserve the effect of coagulation on the RBC travel distance in the nrLFA device. In the last part of the study, the utility of the nrLFA device in veterinary blood coagulation was investigated using various anticoagulated animal blood.

Committee: Andrew Steckl Ph.D. (Committee Chair); Chong Ahn Ph.D. (Committee Member); Marc Cahay Ph.D. (Committee Member); Giovanni Pauletti Ph.D. (Committee Member); Kyle Traver M.S. (Committee Member) Subjects: Electrical Engineering

PhD, University of Cincinnati, 2018, Engineering and Applied Science: Electrical Engineering

As point-of-care technology continues to evolve, more research efforts are focusing on wearable health monitoring devices. Wearables grant unprecedented potential to continuously monitor vast amounts of vital information about a user's well-being and do so without need for the attention of the wearer or trained personnel. To achieve such a device, developers have been striving to find solutions that offer non-invasive interrogation techniques while still providing access to core physiological information. Recent advances in sweat sensing research strongly meet these criteria and place it on the forefront of the wearables field. Technology developed in these efforts has matured to the verge of realizing an all-in-one system. Upon creation of a few remaining components, all that remains is custom integration of the new and existing technology to produce a high-quality, first generation complete sweat sensing system. In this dissertation, the current status of sweat sensing is first reviewed and the remaining challenges are analyzed to identify handling of ultra-low sample volumes as the core problem. Solutions to this problem are explored through research and experimentation. Improving the low volume sample capabilities of some existing electrode sensor platforms fabrication are first investigated. Next, a novel fluid sampling and transport device with specific advantages to handling nL scale sample volumes is theorized. Demonstration of the sample management device revealed it as the strongest possible candidate to complete integration of the key components needed for a wearable sweat system. Proceeding with this foundation, the new device was then used to integrate a recent breakthrough in wearable iontophoretic sweat stimulation with a biosensor and demonstrated to provide continuous long-term biomarker monitoring in a human subjects study. This system is further validated as a commercially relevant strategy, owing to its versatile design which is mod (open full item for complete abstract)

Committee: Jason Heikenfeld Ph.D. (Committee Chair); Leyla Esfandiari Ph.D. (Committee Member); Rashmi Jha Ph.D. (Committee Member); Richard Murdock Ph.D. (Committee Member); Andrew Steckl Ph.D. (Committee Member) Subjects: Biomedical Research

PhD, University of Cincinnati, 2016, Engineering and Applied Science: Electrical Engineering

Chronic exposure to elevated levels of manganese (Mn) can lead to a wide range of health issues. Both the World Health Organization (WHO) and the US Agency for Toxic Substances and Disease Registry (ATSDR) have established safely limits for Mn in water and blood. To protect public health and the environment, it is critically important to monitor concentrations of Mn, so that clinicians and environmental scientists can take immediate action when necessary. The conventional approaches to monitoring Mn, such as ICP-MS or AAS, are extremely accurate, but are costly and are not suitable for fast response. A point-of-care system featuring electrochemical sensing can meet the requirements of a simple, cost-efficient, but highly sensitive analytical tool. This dissertation describes development of a microscale electrochemical sensor for determination of Mn using cathodic stripping voltammetry. The explored sensors include a copper (Cu)-based sensor with palladium (Pd) film working electrode, a platinum (Pt) sensor, and an indium tin oxide (ITO) sensor. With proper characterization of electrodes and optimization of parameters, a sufficiently low limit of detection (LOD) can be achieved. For example, the Cu-Pd sensor on glass substrate demonstrated LOD of 333.6 nM (18.3 ppb) in pH 9.0, 0.1 M borate buffer. For the Pt sensor, the LOD improved to 16.3 nM (0.9 ppb) in pH 5.5, 0.2 M acetate buffer, with similar performance for the ITO sensor. Using the Pt sensor, trace Mn concentrations were determined in natural water samples (pond water, river water, and well water) and achieved >97% precision and ~90% accuracy when we compared with ICP-MS. Using the ITO sensor, Mn was determined in digested whole blood samples. Ultimately, these results suggest that electrochemical sensors can enable sensitive and accurate on-site determination of Mn in various sample matrices. With additional development, these sensors can be integrated into a user-friendly portable system, which (open full item for complete abstract)

Committee: Ian Papautsky Ph.D. (Committee Chair); Adam F. Bange Ph.D. (Committee Member); Erin Nicole Haynes Dr.P.H. (Committee Member); William Heineman Ph.D. (Committee Member); Andrew Steckl Ph.D. (Committee Member); Philip Wilsey Ph.D. (Committee Member) Subjects: Analytical Chemistry

Master of Sciences (Engineering), Case Western Reserve University, 2016, Biomedical Engineering

Every day, more than 1,000 children are born with sickle cell disease (SCD) in Sub-Saharan Africa. About 50-80% of these children die before the age of five due to lack of diagnosis. Current laboratory methods are too costly and resource-intensive for widespread diagnosis of SCD. The World Health Organization (WHO) has recognized the unmet need for early screening and diagnosis of SCD in newborns, and estimates that 70% of SCD related deaths are preventable with simple, cost-efficient interventions. To address this need, the HemeChip was developed as a point-of-care device for diagnosing SCD. With a finger-prick volume of blood, HemeChip identifies and quantifies hemoglobin types on a strip of cellulose acetate paper that is housed in a micro-engineered chip with a controlled environment and electrical field. The HemeChip results were validated and benchmarked against standard clinical hemoglobin screening methods, such as bench-top electrophoresis and high performance liquid chromatography.

Committee: Umut Gurkan PhD (Advisor); Kenneth Gustafson PhD (Committee Chair); Jane Little MD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Design; Health Care

MS, University of Cincinnati, 2015, Engineering and Applied Science: Computer Engineering

Neurological emergencies occur in millions of Americans every year with frequently devastating results. Examples of these types of emergencies include acute pituitary failure, acute stroke, sub-arachnoid hemorrhage, severe traumatic brain injuries, and acute symptomatic seizures. Traumatic Brain Injury (TBI) is one common neurological condition that has high morbidity and mortality. If not assessed quickly and efficiently, the severity or indicator of underlying injury can be mistaken leading to either catastrophic consequences or the triaging of patients with non-significant injuries to Trauma centers under the suspicion of having a possible TBI. Advanced industry tools such as CT scanners and MRI machines have been used to perform imaging studies for diagnostic, re-evaluation and monitoring purposes inside tertiary care centers. However, these machines are very expensive and bulky while requiring the user to remain still for extended periods of time; which makes them inappropriate for continuous monitoring. The use of these advanced diagnostic technologies to perform a full evaluation of acute diseases is not only critical, but frequently treatment based on evaluation findings makes the transferring to specialized medical centers absolutely necessary. The optimization of diagnostics is critical here as early diagnosis/and or treatment can have a significant impact in increasing or decreasing a patient's chance for survival in the face of prolonged transport or treatment response timing. Currently, there is no efficient time-dependent tool to allow first responders to gather diagnostic information to assess a patient's risk of having acute neurological illness or injury at the point of care. Such a device would facilitate better care and possibly better outcomes for a large group of vulnerable patients. The goal of this research is to develop a non-invasive time-dependent technology for appropriate use in assisting medical providers and first responders with r (open full item for complete abstract)

Committee: Fred Beyette Ph.D. (Committee Chair); Carla Purdy Ph.D. (Committee Member); Philip Wilsey Ph.D. (Committee Member) Subjects: Health Sciences