Small insect-inspired robots have much potential in exploration and have been experiencing a wave of innovation in recent years. Small robots have promise especially in space exploration where each kilogram costs $10,000 to launch, but tiny robots tend to weigh under a gram. However, some problems persist, such as difficulty with landing after flight and hopping mechanisms wearing down after a few uses. Our work focuses on developing a hopping robot that is capable of attaching to an overhanging surface when it jumps and that has durable mechanisms to optimize the number of jumps per bot. The hooking mechanism differs from previous work, usually electrostatic patches, and instead is inspired by the hooked feet of beetles, which is lighter and does not require constant electrical power. For optimizing jumps, we are working to develop a jumping body constructed from and designed for carbon fiber rather than the previously used fiberglass. Carbon fiber has a higher strength to weight ratio and is more elastic than fiberglass, making it efficient for flight and the repetitive motion carried out by the body when bent by the onboard actuator. All designs are created using an iterative design process where parts are micromachined and assembled, then tested for desired qualities. From this, we are aiming to develop an autonomous hopper capable of completing multiple jumps and grabbing without maintenance on any part of the bot.

Cardiovascular disease (CVD) continues as the leading cause of death worldwide. The underlying cause of CVD is atherosclerosis, characterized by fatty plaques in the inner walls of the artery, and exacerbated by oxidative stress, inflammation and immune cells. The high-density lipoprotein (HDL)-associated enzyme paraoxonase-1 (PON1) plays a significant role in protecting against CVD. However, the mechanism of PON1’s protection is not well understood. Our laboratory and others have reported a progressive decrease of PON1 activity in several diseases. Our goal is to understand how PON1 prevents oxidative stress and its potential measurement as an early biomarker of risk of disease. Our hypothesis is that oxidative stress inhibits PON1 enzymatic activity, leading to progression of the atherosclerotic process in CVD. The objective of this research is to generate a mouse model to allow us to study the human enzyme PON1 in induced atherosclerosis in vivo.  Starting from two strains of knockout (KO) mice, we have generated the Pon1/apolipoprotein E (apoE) double KO mouse, known to be susceptible to atherosclerosis. We are now crossing this double KO mouse with Pon1 KO mice that express human PON1 (transgenic human PON1 mice, tgHuPON1). We collect ear punches for DNA extraction and blood from the saphenous vein for activity assays. We use polymerase chain reaction (PCR) genotyping methodology, which amplifies DNA, to identify mice that are KO for mouse Pon1 and apoE and that express human PON1. We run enzymatic assays to determine activity levels of the human PON1 in mice. Once we have created the tgHuPON1/apoE KO mouse, we will feed mice with an atherogenic diet, which will induce subclinical atherosclerosis. This knowledge will contribute to understanding the relationship between PON1 and CVD, and will likely generate a useful biomarker for risk of disease.      

Astrocytes are a type of glial cells in the central nervous system, play a critical role in protecting neuronal signaling by regulating brain homeostasis, synaptic plasticity and transmission, and blood brain barrier functioning in central nervous system. Accumulating evidence has indicated that abnormal behaviors of astrocytic functions, including astrodegeneration and astrogliosis, are implicated as the primary factors contributing to a number of chronic neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Kir4.1 is an inwardly rectifying K+ channel expressed on the projections of astrocytes, which serve important roles in the neuroprotective function of astrocytes, such as maintaining K+ homeostasis and regulating extracellular glutamate. Abnormal expression of Kir4.1 has been reported in certain neurodegenerative diseases, including Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), suggesting a vital role in the development of pathophysiology. However, the association between the molecular mechanism and expression of Kir4.1 and the underlying pathogenesis of AD and PD has been largely uninvestigated. In this study, we have had the critical opportunity to access human post-mortem brain tissue, provided by the University of Washington Alzheimer’s Disease Research Center, and conducted confocal microscopy studies. Through a quantitative immunofluorescense staining approach, we expect to demonstrate a distinct expression pattern of Kir4.1 in various brain regions of AD and PD post-mortem tissues when compared to control subjects. Determining the role this protein has in neurodegeneration may provide new insight into the development of therapeutic targets to ameliorate the progression of AD and PD.

Geothermal flux, the amount of heat from the Earth’s interior that reaches the Earth’s surface, is an important boundary value used when modeling ice sheets in Antarctica and estimating future sea level rise. However, geothermal flux is difficult to measure directly. This research project used a numerical ice and heat flow model to estimate the upper bound for geothermal flux under ice domes in Antarctica. We applied this model to ice domes with identifiable Raymond arches, structures in the internal stratigraphy which form only when the ice is frozen to the bed. We estimated the geothermal flux at which an ice dome’s modeled basal temperature reaches the melting point, thus setting an upper bound, using site-specific values for the accumulation rate, surface temperature, and ice thickness. Where measured basal temperatures are known, we made more precise estimates of geothermal flux. Uncertainty values for the modeled flux values were derived by testing the uncertainty of each input value. Model estimates were compared with Martos et al. (2017) and An et al. (2015) geothermal flux estimates derived from remotely sensed data. Comparisons show that in regions such as the Siple Coast, estimates disagree significantly, while they mostly agree in the Antarctic Peninsula. The results of this project set an upper limit on geothermal flux values that can be used to support past and future geothermal flux estimates at these locations.

Quantum sensing applications require diamonds with high concentrations of high-fidelity NV centers. Here we find we can significantly increase the NV center density in high-purity diamond by over a factor of ten by simple annealing. We perform fifteen anneals starting with 800 °C up to 1100 °C. Throughout each anneal, we track thousands of individual NV centers in a large experiment volume (350x350x500 um³) using a custom confocal microscope. Peak NV density was observed to occur at 980 °C. Spectroscopy measurements also show near ideal NV quantum characteristics for the newly formed centers. With this process, we can optimize NV formation for magnetic field sensing and quantum entanglement applications.

Quantum systems are building blocks for promising new technologies such as fundamental secure communication, quantum computing, and quantum sensing. One quantum system, the diamond nitrogen-vacancy center, presents many of the best traits among scalable qubit candidates. Preferential lattice orientation of nitrogen-vacancy centers, while technically difficult, would improve signal to noise ratios in quantum sensing and efficiency of quantum repeaters. I report defect orientation changes in diamond through week-long diamond anneals at high temperatures. I discuss my techniques to measure, characterize and spatially track thousands of nitrogen-vacancy defects through confocal microscopy to observe orientation changes as a function of annealing temperature. I show conclusive data supporting a critical temperature for achieving nitrogen-vacancy orientation changes and discuss follow on applications.

Filoviruses are a family of viruses including the Ebola and Marburg viruses which pose serious threats to global health, as evidenced by the 2013-2016 West African Ebola outbreak. Lloviu virus (LLOV) is a recently discovered filovirus associated with large bat die-offs in Spain and Hungary. Its effects on humans are unknown; however, similarities to other deadly filoviruses suggest it may have similar infectivity. Live LLOV has not been isolated, hindering vaccine research and development. The goal of my project is to develop a model “pseudotype virus” of LLOV using non-pathogenic vesicular stomatitis virus (VSV) as a backbone expressing LLOV viral envelope glycoprotein. I modified and optimized existing methods used to produce VSV pseudotype viruses by transfecting cells with plasmids expressing the VSV genome, modified to produce LLOV viral envelope glycoprotein. This pseudotyped LLOV can now be used to test vaccines against LLOV and provide insights into this understudied virus.

Von Willebrand Disease (VWD) is a bleeding disorder in which von Willebrand Factor (VWF), a polymeric blood protein, is either completely absent or in a dysfunctional state within the circulatory system. VWF’s function is to respond to shear force through an unfolding conformational change, and it is this unfolding and consequential exposure of platelet binding sites that initiates the blood clotting cascade. Affecting 1% of the entire population, VWD is the most common inherited bleeding disorder. However, few effective treatments exist. A major barrier to understanding VWF function is the absence of human cellular and vascular models that can accurately reconstitute complex phenotypes and molecular mechanisms. Studies of VWF at the cellular and vascular scale can provide important insight into physiological factors that regulate VWF. Human cells are particularly attractive and provide a highly accessible, species-specific model that can be more flexible than mouse models. Current cellular models for VWF functional studies are primarily limited to endogenous VWF secreted from human umbilical vein endothelial cells (HUVECs), which are not immortal, making it difficult to engineer disease models. This project serves to directly address these barriers through the creation and characterization of stable VWF knock-out human pluripotent stem cell lines (hPSC). These cells are immortal and can differentiate into numerous lineages including endothelia. VWF knock-out cells differentiated normally into endothelial cells, as expected, based on cell morphology and endothelial marker expression. The VWF knock-out cells have been confirmed through immunoblot and immunofluorescence to be deficient in various VWF-associated proteins, such as Factor VIII and Angiopoietin-2. We are currently investigating the mechanisms behind these deficiencies and how they relate to the absence of VWF. These findings will enable us to better understand the function of VWF, which will ultimately guide us to discover effective treatments for VWD.

The nitrogen vacancy (NV) center is a point defect in diamond with quantum mechanical spin properties. These properties enable optical nano-scale magnetic field sensing at room temperature, making them highly bio-compatible. To conduct wide-field magnetic field imaging, we require a nano-scale thin surface layer of high NV center density in our diamond samples. We demonstrate optimized sensing capability in our diamonds through growth and processing methods, which create an ensemble of NV centers. With these sensitive samples we use quantum control protocols called double quantum and spin bath driving to reach sensitivities of 60nT/Hz^1/2 over a 0.1 cubic micron pixel. These protocols take advantage of inherent characteristics of the NV center and improve the imaging capability for biological systems.

Dementia is a neurological condition that impairs memory, cognitive functions, and the performance of daily activities. It is estimated that 5.5 million Americans suffered from dementia in 2018. Currently, the predominant method used to treat persons with dementia is through pharmacological means. However, through reviewing current research, we have found evidence to suggest that cognitive behavior therapies (CBT) may be more beneficial to patients, with the potential to reverse some symptoms of dementia. Our study aims to improve CBT through virtual environments. Virtual Reality (VR) is not merely a visual platform but an immersive environment that stimulates the brain in the same way real environments do. However, in VR we can track certain markers like head and eye movement, metrics that can be valuable in tracking the progression of the disease as well. We have developed a virtual experience that can calm and stimulate seniors while being able to track a person’s ability to perform free recall and spatial recognition through a series of memory games. This experience has the potential to have both therapeutic and diagnostic capabilities, as well as provide insight into how VR can affect memory. Over the past 6 months, our research team has worked with seniors at the Greenwood Senior Center to test different virtual reality platforms such as the Oculus Go and HTC Vive, as well as various virtual environments. Using our experience from the center our team is creating a platform tailored to fit seniors who are affected by dementia. In the near future, our team will be volunteering at a local assisted living facility to work with these seniors. This project will offer understanding of how implementing VR therapy can improve patients’ morale and cognitive capabilities, as well as exploring the use of VR as a diagnostic tool.

Efforts to engineer flying micro-robots (~50mg) are motivated by their potential advantages relative to larger robots, such as greater deployment numbers at the same cost. There are significant developments in flapping wing robots at insect-scale; however, little advancement has been made in the development of robots with ionic actuation using electrohydrodynamic (EHD) thrust. This thrust is generated through the ionization of air particles and momentum transfer of these positive ions with neutral air molecules. EHD thrusters have used collector grids and emitter wires to generate a thrust for controlled flight. In this research, we design and fabricate a 1.8 x 2.5 cm micro-thruster that weighs a total of 43 mg including the carbon fiber collector grid, four blue tempered steel emitters, and eight fiber optic glass tubes. This robot is hand-assembled using a laser fabricated external fixture. Electrodes of the robot are fabricated using a laser based system. The whole robot takes a total of 20 minutes to assemble. Emitters are supplied with a high voltage (~2.5kV) using a bundle of 51-gauge insulated copper wires. Similar wire is used for grounding the collector grid. A parametric study is carried out to optimize the physical parameters of the robot. Experiments performed in this research show that the thrust generated is larger than the weight of the robot.