Doctor of Philosophy, The Ohio State University, 2019, Biomedical Engineering

Natural plant surfaces, such as lotus leaves, rice leaves, and rose petals, possess unique wetting properties. Lotus leaves contain hierarchic micro/nano-topographies with a waxy coating and exhibit isotropic and ultralow flow resistance. A water droplet can roll off the surfaces that are tilted at a small angle regardless of the tilting direction. Rose petals also own hierarchic micro/nano-topographies, but with larger characteristic dimensions. The petal surfaces possess a high water flow resistance and can pin small water droplets on the surfaces even if the surfaces are positioned vertically or upside down. On the other hand, the petal surfaces are superhydrophobic so that the droplets can move without leaving any residue. A rice leaf has linearly arranged micro/nanopapillae, which lead to anisotropic flow resistance that can move water droplets preferably along the alignment. In this dissertation, bioinspired smart surfaces are investigated to mimic the distinct wetting properties on natural plant surfaces. In-plane mechanical stretching of the smart surfaces can dynamically and repeatedly modulate the characteristic dimensions of the micro-wrinkles, and in turn switch the surface wetting properties. With proper hydrophobic treatment, the wetting properties of the smart surfaces can be switched between lotus-like and rose-like; or lotus-like and rice-like. The surface wetting states can also be changed from Cassie Baxter state to Wenzel state by mechanical straining. In order to validate the efficacy of the smart surfaces in biomedical applications, droplet-based open channel microfluidics, and strain activated drug release are established respectively. In particular, lossless droplet transfer, droplet splitting, and modulation of droplet mobility are demonstrated on the lotus-rose switchable smart surfaces. Dynamic modulation of wetting anisotropy is exhibited on the lotus-rice switchable smart surfaces. Mechanical strain activated stepwise drug releas (open full item for complete abstract)

Committee: Yi Zhao (Advisor); Derek Hansford (Committee Member); Jun Liu (Committee Member); Kubilay Sertel (Other) Subjects: Biomedical Engineering

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

Sorting and purification of target cells from complex cellular samples is critical for downstream cell biology research, biomedical research and clinical diagnostics. In this work, a novel microfluidic platform is developed to achieve size-based sorting of cells with high performance and systematic versatility. The platform uses inertial effect of fluid and microscale vortices in designed microfluidic units to align and sort cells. A microfluidic unit was first developed to enable bimodal sorting of cells with high sorting resolution and tunability. Microparticle mixture with only 2 µm difference was continuously sorted with > 90% efficiency. Two sorting units were then integrated into specific arrangements to enable versatile cell sorting functions. A serial sequencing arrangement enabled new multimodal sorting function. Multi-sized or heterogeneous microparticle mixtures were sorted continuously into three subpopulations of different sizes with > 90% efficiency. Alternative arrangement of the two units enabled new double sorting and purification function. The larger target cells can be extracted from the small non-target cells two times sequentially yielding highly purified target cell product. Spiked human cancer stem-like cells (HuSLCs) were sorted from human blood samples with enriched concentration and significantly enhanced purity. The two distinct arrangements exhibit the systematic versatility of the vortex cell sorting platform for efficient sorting of complex cellular samples which will open new opportunities for size-based cellular sample preparation in cell biology, biomedical research and clinical diagnostics.

Committee: Ian Papautsky Ph.D. (Committee Chair); Chong Ahn Ph.D. (Committee Member); Chia Chi Ho Ph.D. (Committee Member); Susan Kasper Ph.D. (Committee Member); Andrew Steckl Ph.D. (Committee Member) Subjects: Biomedical Research

MS, University of Cincinnati, 2013, Engineering and Applied Science: Computer Engineering

Physical defects in digital microfludics chips (DMCs) can be very complicated and extremely difficult to find precise models, because each defect may occur anywhere. In this thesis, we develop high-level abstract fault models based on investigating the faulty and fault-free behaviors of droplet moving. Two new fault models that were not found previously are proposed to enhance the reliability of DMCs. We believe that the high-level fault models can completely cover all defects involving two cells in a DMC array. Based on the new high-level fault models, we propose march algorithms (march-d and march-p/p+) to generate test patterns that can detect and distinguish fault types for each faulty digital microfludics chip. This is accomplished by merging both march-d and part of march-p without causing too much test length increase. These algorithms are implemented into a FPGA board attached to the simulated digital microfluidics chip such that built-in self-test can be accomplished without human intervention. We also develop an EDA tool and simulation platform for the proposed DMC-BIST system. Experimental results demonstrate that the proposed fault models, test and fault type distinguishing methods, built-in self-test circuit design, and emulation tool can effectively and efficiently achieve high quality test with minimal test cost.

Committee: Wen Ben Jone Ph.D. (Committee Chair); Xingguo Xiong PhD (Committee Member); Ian Papautsky Ph.D. (Committee Member) Subjects: Computer Engineering

PhD, University of Cincinnati, 2009, Engineering : Electrical Engineering

Filtration and separation of particles has numerous industrial and research applications in biology and medicine. In this work, inertial microfluidics is used to develop devices for continuous and passive separation and filtration of particles. Although particles are generally expected to follow laminar flow streamlines in the absence of external forces, inertial forces can cause particles to migrate across microchannels in an accurate and predictable manner. Thus, this work demonstrates how a simple spiral microfluidic channel can be used for high-throughput separation and filtration of particulate mixtures by exploiting these inertial forces and taking advantage of Dean forces present in curved channels. The developed technique was used to demonstrate a complete separation between 1.9 µm and 7.32 µm diameter polystyrene particles and filtration of red blood cells. The inertial forces can also be modulated by controlling fluidic shear in microchannels with rectangular, high aspect ratio cross-section in order to cause preferential particle migration. This approach was used successfully to demonstrate a complete filtration of 1.9 µm and 780 nm diameter particles in straight rectangular microchannels. The ability to continuously and passively focus particles based on size at high flow rates in microchannels is expected to have numerous applications in high-throughput bioparticle separation and filtration systems. The simple planar nature of the devices should permit easy integration with the existing lab-on-a-chip (LOC) systems.

Committee: Ian Papautsky PhD (Committee Chair); Chong Ahn PhD (Committee Member); Jason Heikenfeld PhD (Committee Member); Rupak Banerjee PhD (Committee Member); Dionysios Dionysiou PhD (Committee Member) Subjects: Electrical Engineering

Master of Sciences, Case Western Reserve University, 2025, Materials Science and Engineering

Silicon nitride fluidic devices show promise in the application of high-heat-flux cooling for high-powered electronics. Such devices can be manufactured from layered ceramic tapes if the material and process are sufficiently developed. This work approaches the manufacture of such devices through three investigations. Firstly, the organic composition of two selected silicon nitride tapes was developed and refined, and an automated segmentation method was used to compare the particle size distribution (approximately 0.1 μm-10 μm) of tapes as a function of location. Secondly, various processes were refined in the manufacture of fluidic devices from alumina tapes, namely the identification of an appropriate lamination procedure, a prediction of shrinkage during sintering, and the development of flattening techniques to reduce curvature in the devices. Lastly, the mechanical behavior of green PVB-based tapes has been characterized as a function of tape stack thickness, strain rate, and surface, through the use of microindentation.

Committee: Jennifer Carter (Committee Chair); Chirag Kharangate (Committee Member); John Lewandowski (Committee Member); Mark De Guire (Committee Member) Subjects: Materials Science

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Engineering

Glioblastoma (GBM) is the most common malignant brain tumor, and even with standard treatment, median patient survival is only about 15 months. This poor prognosis is likely due to the extreme heterogeneity of GBM tumors and a unique tumor microenvironment (TME) that drives tumor cell invasion, adaptive drug resistance, and recurrence after treatment. Additionally, the blood-brain barrier (BBB) prevents most therapeutics from reaching the tumor. The failure of many promising drug candidates may indicate that current preclinical models do not accurately replicate tumor biology and human BBB function. Recent advances in bioengineering technologies have enabled the development of complex human cell based in vitro models that can be used to study disease mechanisms and test therapeutics. The goal of this dissertation was to utilize these tissue engineering and biofabrication tools to develop in vitro models that can be used to advance our knowledge of certain aspects of the GBM tumor microenvironment. First, a novel hydrogel was developed that supports physiological astrocyte phenotype. We used this hydrogel to study astrocyte activation in response to GBM cell secreted factors to better understand how astrocytes contribute to neuroinflammation in GBM. Second, we developed a 3D microfluidic blood brain barrier model using a brain mimetic ECM hydrogel, and third, we applied this 3D BBB model and demonstrated that it can be used to investigate how different populations of GBM tumor cells influence BBB permeability. These new bioengineered model systems will allow us to further investigate disease mechanisms and allow for the testing of novel drugs to treat GBM in the future.

Committee: Aleksander Skardal (Advisor); Monica Venere (Committee Member); Jonathan Song (Committee Member); Jennifer Leight (Committee Member) Subjects: Biomedical Engineering

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

PhD, University of Cincinnati, 2023, Arts and Sciences: Chemistry

The importance of the gut-brain axis has become increasingly apparent, insights into the neurotransmission along this axis could provide crucial information into roles along the gut-brain-immune axis. Physiologic culture methods of ex vivo tissue slice models are imperative to assess physiological function ex vivo. Microfluidics has been adapted to improve the physiological environment of current culture methods. In this thesis I have detailed microfluidic improvements to analytical detection methods, single organ slice culture devices and multi-organ communication devices. The first chapter details the importance of the gut-brain axis and the communication pathways along this connection. Detection methods for this multi-organ communication are also detailed in the first chapter. Wrapping up this chapter the need to expand our ex vivo culture platforms currently in the field is discussed. In the second chapter, I detail a microfluidic electrochemical flow cell to improve the current experimental procedure. The T-channel device design followed by a long microfluidic channel facilitate full mixing of solutions before the electrode surface. Flow rates can be varied to allow for a full concentration curve to be performed from a single stock analyte solution. This device reduces human error drastically in the experiment and decreases time and cost due to the microfluidic nature of the device. Chapter three describes a culture platform for ex vivo intestinal slices that recreates the physiological oxygen gradient that occurs in the intestine. Flow rates of oxygenated and deoxygenated media can be varied to allow for strategic delivery to different sized slices. The delivery of this gradient was proven to remain steady over the course of an hour. This device also provides an open culture platform for easy coupling with external detection methods such as fast scan cyclic voltammetry and microscopy techniques. Chapter four details a multi-organ (open full item for complete abstract)

Committee: Ashley Ross Ph.D. (Committee Chair); Ryan White Ph.D. (Committee Member); In-Kwon Kim Ph.D. (Committee Member); Leyla Esfandiari Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy, Case Western Reserve University, 2023, Biomedical Engineering

In many chronic inflammatory diseases, the vascular endothelium becomes pathologically permeable due to conditions like angiogenesis and production of growth factors and inflammatory cytokines (e.g., histamine, bradykinin, etc.). In cancer, this process can be exploited for delivery of nanoparticles to tumors via the enhanced permeability and retention (EPR) effect. However, nanoparticle-based therapeutics reliant on the EPR effect have led to inconsistent results in patients. This is due to many factors, with a significant one being heterogeneous tumor vascular architecture and morphology both between patients and within a single tumor. Transport of the nanoparticle to the tumor and into the parenchyma is complicated by uptake by the immune system, ineffective margination, and inefficient extravasation. Guidance is needed to inform clinicians on what therapies may be most effective for each patient. Effective guidance could reduce health-care costs and negative side effects of medication. An inexpensive, safe, non-invasive, and real-time imaging method that has high temporal and spatial resolution may be capable of categorizing the extent of vascular permeability in tumors and once validated, personalize therapeutic regimens for patients. Such a tool could be used not only for tumors, but for all diseases involving pathologically permeable vasculature. With this goal in mind, the objective of this thesis is to work toward development of a real-time method for evaluating vascular permeability over the entire tumor using novel nanobubble (NB)-based contrast-enhanced ultrasound (CEUS). This work builds upon dynamic CEUS protocols used clinically with microbubbles (MBs). NBs, which are 100-400 nm in diameter, are approximately 10x smaller than MBs and have been shown to extravasate into the tumor interstitium. To reach the final objective of this work, NB dynamics from intravenous injection to retention in the tumor must be studied. To this aim, in vitro studies con (open full item for complete abstract)

Committee: Agata Exner (Advisor); Horst von Recum (Committee Chair); Anirban Sen Gupta (Committee Member); Aaron Proweller (Committee Member) Subjects: Biomedical Engineering; Medical Imaging; Medicine; Nanoscience; Nanotechnology; Oncology; Radiology

Doctor of Philosophy, The Ohio State University, 2023, Mechanical Engineering

DNA origami technology allows for the design and fabrication of biocompatible and 3-D functional nanodevices via molecular self-assembly for various biological applications including cell function regulation, disease therapy and biomolecular detection. Biocompatibility and programmability of DNA molecules lead into the development of complex and functional DNA nanodevices that can work in biological media and living systems. Stability and functionality of DNA nanodevices compared to DNA molecules itself, make it an effective approach for cell modulation and payload delivery. The field of nanomedicine, has developed a path to detect and fight infectious disease using nanomaterials and DNA nanostructures are novel additions to the nanomaterial collection, providing great progress in diagnostics and therapy. Nucleic acids, proteins and whole pathogens are among the viral and bacterial targets which can be detected using DNA nanostructures. In this dissertation, we report four studies on biological applications of DNA origami in detection and modulation of biological cues. We establish the successful incorporation of DNA nanodevices on the cell membrane and report a robust method to monitor live cell interactions with biomolecules in their surrounding environment. Our results establish the integration of live cells with membranes engineered with DNA nanodevices into microfluidic chips as a highly capable biosensor approach to investigate subcellular interactions in physiologically relevant 3-D environments under controlled biomolecular transport. Moreover, we propose a novel complex DNA platform for modulating the gap in intercellular junctions and finally establish three DNA nanodevices for the detection of viral and bacterial nucleic acids in human samples. Collectively, the findings of this dissertation establish a foundation on functionality of nanodevices for biological applications.

Committee: Carlos Castro (Advisor); Vishwanath Subramaniam (Committee Member); Comert Kural (Committee Member); Jonathan Song (Committee Member) Subjects: Biomedical Engineering; Biophysics; Mechanical Engineering; Nanotechnology

Doctor of Philosophy, Case Western Reserve University, 2022, EMC - Mechanical Engineering

Cellular processes strongly regulate the biophysical and biomechanical properties of each blood cell including density, adhesion, and motility, all of which can rapidly change during various healthy and pathological states. To have a better understanding of the cellular processes, an assessment of the biophysical and biomechanical signatures of single cells is needed. Microfluidics has the remarkable ability to mimic the physiological environment of microvasculature, providing a means to better characterize biomechanical and biophysical signatures of blood cells, such as adhesive interactions between different blood cells. As a result, microfluidics has found applications in studies of many different pathophysiologies that stem from altered biomechanical and biophysical properties of blood cells. Despite the advances in microfluidics for the characterization of the biophysical and biomechanical properties of blood cells, the use of microfluidics for mechanistic and mechanobiology studies remains limited due to a lack of standardization and single-cell level imaging. Microfluidics can harness image analysis for standardized characterization of fundamental properties of single cells and reveal subpopulations in heterogeneous cell populations to unfold the mechanobiology and mechanisms of physiology reliably. This dissertation presents the design and engineering of standardized microfluidic systems that utilize image analysis at various technical complexity levels (i.e., manual pixel-to-pixel distance measurements, and automated computer vision with and without machine learning). These microfluidic single-cell level imaging systems demonstrate effective multi-variate measurement of blood cells' biophysical and biomechanical properties and inform the investigation of microcirculatory cellular action mechanisms. The specific aims of this dissertation were: 1) To develop a microfluidic magnetic levitation platform that can perform size and density measurements of single r (open full item for complete abstract)

Committee: Umut Gurkan (Advisor); Bryan Schmidt (Committee Chair); Michael Hinczewski (Committee Member); Ozan Akkus (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Biophysics

Doctor of Philosophy, The Ohio State University, 2022, Chemical Engineering

Despite the underlying role of hypoxia and oxidative stress in vascular and inflammatory diseases, little is understood about its role in early disease progression and no therapeutics exist to combat it. Hypoxia is suspected to disrupt the function of the endothelium, the inner lining of cells in all vessels which is responsible for regulating exchange between nutrients and waste metabolites in the blood stream and tissues. Due to the vital and far-reaching functions of the endothelium in modulating vascular tone, inflammatory pathways, and the formation of new vessels, endothelial dysfunction often precedes and can be propagated in vascular disease. Consequently, studying the relationship between hypoxia and endothelial dysfunction is an area of great interest in identifying potential therapeutic targets for early intervention. A pathophysiology of particular interest in this work is preeclampsia (PE), a pregnancy disorder which is poorly understood. In PE, early vascular dysregulation leads to later appearance of clinical symptoms. Hypoxia is intimately involved in the progression of PE and its potentially devastating effects on fetal development. No therapeutic interventions currently exist for PE. As such, PE is an excellent environment in which to investigate whether oxygen (O2) modulation can rescue vascular dysregulation. One promising candidate for therapeutically alleviating hypoxia associated with the vascular disease state is hemoglobin-based O2 carriers (HBOCs). However, commercially available HBOCs contain low molecular weight (LMW) species which induce cytotoxicity due to extravasation. This work focused on synthesizing and characterizing high molecular weight (HMW) polymerized human hemoglobins (hHb)(PolyhHbs) in order to achieve a therapeutic O2 carrier with an improved safety profile. To this end, a tunable platform replicating human microvasculature was developed and used to evaluate HMW PolyhHb's potential for extravasation and endothelial (open full item for complete abstract)

Committee: Andre Palmer (Advisor); Eduardo Reategui (Committee Member); Jeffrey Chalmers (Committee Member); Jonathan Song (Advisor) Subjects: Chemical Engineering

Doctor of Philosophy, The Ohio State University, 2022, Biomedical Engineering

Microscale flows are central to many different physiological and biological systems. As such, microfluidic technology, which provides the means for efficient flow manipulation at the microscale, has emerged as an important tool for numerous biomedical applications, such as perfusion-based cell culture and control of complex cell microenvironments. Yet, one research area ripe for further exploration is the application of microfluidic technology for characterizing the physical properties of biomaterials-based matrices. Biomaterials focused on recapitulating the native three-dimensional (3-D) extracellular matrix (ECM) and the interstitial space surrounding tissue provide controlled conditions for studying physiological function. Careful control of ECM properties, changing parameters such as mechanical stiffness enables researchers to investigate different developmental processes alongside distinct physiological and pathological environments. After a brief introduction, this dissertation describes three major parts that define the application of microscale flow phenomena to unravel biomaterial and biological properties of reconstituted tissue. Part 1 (Chapter 2-4) emphasizes the need to describe the initial conditions by studying the kinetics of ECM hydrogels and connecting these to their physical properties. Here, I expand on a characterization framework that probes the biophysical properties of ECM based materials, measuring mechanical stiffness, convective transport via microfluidics, matrix architecture via confocal reflectance, and ECM polymerization kinetics. While these properties are commonly characterized individually, a combined approach is necessary to comprehensively understand how ECM composition influences the biophysical properties that direct cellular responses and fates. For collagen-based ECM hydrogels, the material properties can start being adjusted in the pre-polymerization stage. Therefore, we can quantify how small changes in the prepolymer sta (open full item for complete abstract)

Committee: Jonathan Song (Advisor); Gunjan Agarwal (Committee Member); Daniel Gallego Perez (Committee Member); Gina Sizemore (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, Case Western Reserve University, 2022, Biomedical Engineering

Paracrine signaling is challenging to study in vitro, as conventional culture tools dilute soluble factors and offer little to no spatiotemporal control over signaling. Microfluidic chips offer potential to address both of these issues. However, few solutions offer both control over onset and duration of cell-cell communication, and high throughput. This dissertation details the development of a microfluidic chip designed to culture cells in adjacent chambers, separated by valves to selectively allow or prevent exchange of paracrine signals. Several versions of the chip were developed, culminating in a chip featuring 128 individually-addressable chambers arranged in 32 sets of 4 chambers; 16 fluidic inputs; and 2 outputs. The chip enables a wide range of cell culture studies including co-culture and can support assays with optical readouts such as immunocytochemistry, as well as cell or media recovery. We demonstrate the ability of the chip to support culture of a variety of cells including cell lines and primary cells, and validate its use for co-culture studies by showing that HEK293Ta cells respond to signals secreted by RAW 264.7 immune cells in adjacent chambers, only when the valve between the chambers is opened. In parallel, a pneumatic controller was developed to operate microfluidic chips, offering manual and automated control via a PC interface of the hardware which features pressure sources, high-precision digital pressure regulators and arrays of up to 32 solenoid valves.

Committee: Horst von Recum (Committee Chair); Samuel Senyo (Advisor); Umut Gurkan (Committee Member); Miklos Gratzl (Committee Member); Harihara Baskaran (Committee Member) Subjects: Biomedical Engineering; Computer Engineering; Electrical Engineering

PhD, University of Cincinnati, 2021, Arts and Sciences: Chemistry

Guanosine is a crucial molecule within the central nervous system known to play a role in neuromodulation and protection in the instance of chemical or physical damage to the brain. Neurochemical release is a dynamic process, necessitating an analytical method that can capture rapid and subsecond signaling events. Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes is an electrochemical technique enabling detection of rapidly released electroactive compounds. In this dissertation, I have detailed an FSCV technique for the quantitation and characterization of dynamic guanosine events within living brain tissue. In the first chapter, I describe the chemistry and neurobiology of guanosine, covering its role within the central nervous system, the metabolic pathways of guanosine and its regulation, and its receptors and transporters. I also describe extant and popular detection techniques for guanosine and its sister compound adenosine. In Chapter 2, I describe the guanosine FSCV waveform I developed for my first graduate project. Here, I go into detail regarding the full characterization of this waveform and present a proof-of-concept for in-tissue detection of guanosine. In the following chapter, I present an additional FSCV waveform allowing for the codetection of both guanosine and adenosine. This waveform is a modified version of the adenosine waveform which enables simultaneous detection of the purine ribonucleosides. This waveform could prove useful in the future for codetection of the ribonucleosides, as earlier studies have suggested an intricate interaction between guanosine and adenosine with important downstream modulatory effects. In the fourth chapter, I use the guanosine waveform to detect endogenous, spontaneous guanosine transients ex vivo. Guanosine events were recorded during a control period and in response to a drug and neurochemical injury. This study marks the first ever recordings of subsecond, dynamic guanosine events in the brain (open full item for complete abstract)

Committee: Ashley Ross Ph.D. (Committee Chair); Ryan White (Committee Member); Mark Baccei Ph.D. (Committee Member); Noe Alvarez Ph.D. (Committee Member) Subjects: Chemistry

Master of Science in Bioengineering, University of Toledo, 2021, Bioengineering

Triple negative breast cancers (TNBCs) are an extremely aggressive subtype of breast cancer that is difficult to treat due to the lack of the typical targeting mechanisms (ER, PR, HER-2) present in other breast cancers. Literature suggests that inducing necroptotic-immunogenic cell death in cancer cells may be a viable approach to treat this subtype. Preliminary studies performed utilizing a novel chemotherapeutic, TPH104c, indicate that this approach is successful. Furthermore, conventional, apoptosis inducing chemotherapeutics such as Paclitaxel are known to damage ECs in microvessels, facilitating cancer cell invasion and metastasis. TNBCs also eventually build resistance against conventional chemotherapeutics. This study established a physiologically relevant TNBC microenvironment consisting of a co-culture of ECs and Paclitaxel resistant cancer cells. Biological assays were performed to simultaneously evaluate the effects of TPH104c and Paclitaxel on ECs and resistant cancer cells. The results of this study demonstrate the safety of TPH104c to ECs while maintaining similar cytotoxicity to cancer cells compared to Paclitaxel at their respective IC50.

Committee: Yuan Tang (Advisor); Eda Yildirim-Ayan (Committee Member); Brent Cameron (Committee Member); Amit Tiwari (Committee Co-Chair) Subjects: Biomedical Engineering

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

Master of Science in Biomedical Engineering, Cleveland State University, 2021, Washkewicz College of Engineering

Nanoparticles have a wide range of applications in biomedicine, catalysis, energy, semiconductors, and consumer products, to name a few. Conventionally, batch synthesis of a variety of nanoparticles is achieved using bottom-up (e.g., wet methods, nucleatedgrowth, microbial synthesis) or top-down (e.g., milling) approaches. However, the reactions, especially in bottom-up approaches, could be time and resource intensive when optimizing for the effects of reaction parameters and their interplay on nanoparticle characteristics and purity. Microfluidic platforms could help overcome these limitations by enabling high-throughput reactions, combinatorial approaches, in situ monitoring capabilities, and utilizing fewer reactant volumes. The aim of this study is to optimize the synthesis of three different types of nanomaterials: poly-lactic-co-glycolic acid (PLGA) nanoparticles, gold (AuNPs) nanoparticles, and lead iodide perovskite nanoplatelets (PNPs), using two types of microfluidic mixers: the reverse staggered herringbone (SHB) mixer and S-shaped Dean mixers. The effect of variables such as the inlet flowrate into the device ports, reactant compositions and mole ratios, and mixer type was investigated to identify the optimal synthesis conditions, i.e., the conditions leading to narrow and uniform size distributions, for each type of nanomaterial in these micromixers. The outcomes from these microfluidic mixers were compared to their counterparts from batch synthesis. Future studies could test the applications of such nanoparticles in targeted imaging and drug encapsulation.

Committee: Chandrasekhar Kothapalli (Advisor); Geyou Ao (Committee Member); Petru Fodor (Committee Member) Subjects: Engineering

Master of Science, The Ohio State University, 2021, Biomedical Engineering

Triple negative breast cancer (TNBC) is the deadliest breast cancer subtype occurring with highest frequency in women of African ancestry. Less access to affordable health screening and insurance in women of low socio-economic status limits early diagnosis of TNBC contributing to increased mortality in this group. New, affordable diagnostic methods are urgently needed for earlier detection of TNBC in disadvantaged populations. Our group has determined that the two closely related RAL GTPases, RALA and RALB, have disparate roles in TNBC tumor growth. These G proteins have also recently been implicated in the production and secretion of extracellular vesicles (EVs). EVs secreted by breast cancer cells may serve as valuable diagnostic tools. We have developed microfluidic devices for the capture of EVs and analysis of EV RNA and protein contents. In this study, we optimize these devices for the capture of EVs secreted by TNBC and determine the consequences of RALA/RALB knockdown on total and CD63+ EV production and composition. MDA-MB-231 TNBC cells stably expressing shRNAs targeting RALA, RALB or a control shRNA were used in this study. EVs were collected from serum-free conditioned medium by ultracentrifugation (UC) or ultrafiltration and purified through a microfluidic device. Herringbone-patterned PDMS microfluidic devices were prepared using soft lithography. In a vacuum plasma chamber, PDMS and a glass slide were activated and bonded to create a sealed chamber. Devices were functionalized by introduction of 0.5 % [3-(2-aminoethylamino)propyl]trimethoxysilane in ethanol, followed by 2.5% glutaraldehyde in DI water. Finally, CD63 antibody was flowed through the device. Modeling in COMSOL was utilized to optimize the flow rate for EV capture. UC-purified EV solution was passed through the device to capture CD63+ vesicles which were released with a pH 2.2 glycine-HCL buffer, and immediately neutralized with a pH 8.5 Tris-HCL buffer. EVs from UC were characterized wit (open full item for complete abstract)

Committee: Steven Sizemore (Advisor); Derek Hansford (Advisor) Subjects: Biomedical Engineering

Master of Science, The Ohio State University, 2021, Mechanical Engineering

We present a resource-efficient approach to fabricate and operate a micro-nanofluidic device that uses cross-flow filtration to isolate and capture liposarcoma derived extracellular vesicles (EVs). The isolated extracellular vesicles were captured using EV-specific protein markers to obtain vesicle enriched media, which was then eluted for further analysis. Therefore, the micro-nanofluidic device integrates the unit operations of size-based separation with CD63 antibody immunoaffinity-based capture of extracellular vesicles in the same device to evaluate EV-cargo content for liposarcoma. The eluted media collected showed ~76% extracellular vesicle recovery from the liposarcoma cell conditioned media and ~32% extracellular vesicle recovery from dedifferentiated liposarcoma patient serum when compared against state-of-art extracellular vesicle isolation and subsequent quantification by ultracentrifugation. The results reported here also show a five-fold increase in amount of critical liposarcoma-relevant extracellular vesicle cargo obtained in 30 minutes presenting a significant advance over existing state-of-art.

Committee: Shaurya Prakash (Advisor); Raphael Pollock (Committee Member) Subjects: Engineering; Mechanical Engineering; Nanotechnology