BME Seminar Series: Colin Hisey, Jennifer Malik, Lauren Cosby, & Alexis Burns
"Microfluidic Tool Development for Characterizing Clinical Cancer Samples"
Advisor: Dr. Derek Hansford
Micro and nanotechnology allow us to better understand and quantify the behavior of aggressive forms of cancer by interacting with cells and vesicles at the scale in which the disease progression truly takes place. Microfluidic devices in particular allow precise fluidic control and low reagent use, improving the cost, speed and precision of many analytical techniques that were conventionally done using bench-top systems. We have developed two distinct microfluidic platform devices which significantly improve the current standards of cell migration analysis and biomarker-specific exosome isolation. The first device utilizes hydrodynamic traps embedded in a PDMS channel to seed individual cancer cells onto microfabricated biomimetic polymer substrates. The predictable seeding location and 1D migration path simplifies the quantification of the cells’ migratory behavior, and will allow the testing of different levels of potential anti-migration therapeutic agents simultaneously. The second device uses an antibody- functionalized and herringbone grooved PDMS channel to capture and release in-tact exosomes directly from ovarian cancer serum for downstream biochemical analysis, decreasing the process time and increasing specificity relative to the conventional ultracentrifugation protocols. For both devices, the fabrication techniques and optimization processes will be explained in detail, as well as the current research being done to enhance their clinical utility.
"Computational Modeling of Eustachian Tube Dysfunction and Enhanced Drug Delivery in the Respiratory System"
Advisor: Dr. Samir Ghadiali
Otitis Media (OM) is the most commonly diagnosed condition in young children and dysfunction of an upper respiratory airway, the Eustachian tube (ET), is the primary cause of chronic OM1. Although several pharmaceutical agents have been proposed to treat ET dysfunction, a major limitation for clinical translation of these therapies is the efficient delivery of these pharmaceutics to the nasopharyngeal (NP) orifice of the ET. Specifically, although intranasal administration of these agents is the most feasible clinical option, it is not clear what fraction of the inhaled compounds would be transported to and deposited on the NP orifice. It is also not clear how efficiently these agents would spread or diffuse into the ET lumen. The goal of this study is to use computational tools to first characterize how patient-to-patient variability in ET structure and mechanics alters therapeutic efficiency and then use computational fluid dynamics (CFD) to investigate how different inhalation conditions, surface transport properties and particle formulations influence drug transport in the nasal cavity to the NP orifice of the ET.
"Preclinical Delivery of Fractionated Black Raspberry Phytochemicals to Oral Epithelial Cells Using Lipid and Polymer Nanoparticles"
Advisor: Dr. Jessica WinterOral cancer is the sixth most prevalent cancer worldwide with an estimated 51,540 new cases occurring in the United States this year. Through in vitro, in vivo and human clinical trial studies, black raspberries (BRBs) and their bioactive compounds have exhibited significant anticancer activities. These activities are attributed to the complex mixture of phytochemicals present in BRBs. While, the roles for anthocyanin-rich hydrophilic compounds are often emphasized due to their inherent bioavailability, our research focus includes the poorly bioavailable carotenoid-rich lipophilic phytochemicals. To accurately evaluate anticancer efficacy, it is necessary to increase bioavailability and delivery to target tissues. Our studies developed and optimized a delivery vehicle for the lipophilic BRB phytochemical, lutein. In doing so, we further evaluate phytochemical encapsulation, growth inhibition, release kinetics, and gene expression in oral epithelial cells (normal, premalignant and malignant) that support cancer chemopreventive activities. Nanoparticles are made via sonication and liquid-liquid electrospray flash nanoprecipitation (LLE-FNP) methods using PHOSPHOLIPON 90G® (P90G), polystyrene-polyethylene oxide (PS-PEO) or polycaprylactone-polyethylene glycol (PCL-PEG) co-block polymers. Encapsulation efficiency (EE) is characterized utilizing standard curves and UV-VIS spectroscopy. Particle size distribution is evaluated using transmission electron microscopy (TEM). Our data demonstrates that LLE-FNP serves as a better synthesis technique compared to sonication. Additionally, PS-PEO micelles have the highest EE as compared to PCL-PEG and P90G and average 40nm in diameter. Initial in vitro analyses show growth inhibition and increased cell granularity in human oral epithelial cell types due to the presence of lutein emulsion at 5uM and higher. Further analysis is being completed to evaluate release kinetics and biological activity of micelle systems to compare with lutein emulsion. With successful completion of this work, we will establish a new chemopreventive nutraceutical to combat the onset, development and recurrence of oral cancer.
"Primitive pathways and neural networks for upper limb movement classification"
Advisor: Dr. John Buford
Currently, there is a lack of methods and equipment to monitor the daily activities of stroke patients. Research has shown that patients who practice functional movements at home along with outpatient therapy show better improvement than patients that do not. Movements produced by patients recovering from stroke tend to reflect outputs typical of the reticulospinal system. This supports the concept of reticulospinal neuron participation in the recruitment of muscles otherwise impaired by stroke. We hypothesized that pontomedullary reticular formation neurons in the brainstem will show significant electrical modulation during double-reciprocal bilateral upper limb exertion. Recording from two non-human primates, M. fascicularis, during a bimanual isometric force task similar to BATRAC we found that 48% of the task-related PMRF neurons recorded showed significant modulation during double-reciprocal bilateral upper limb tasks. The other 52% of cells showed significant modulation during all bilateral upper limb tasks, including symmetrical bilateral exertion. Significant neuron firing patterns between different types of movement were identified enabling us to conclude pontomedullary reticular formation involvement in specific bilateral exertion tasks. With decreased upper limb motor function being a common side effect of cortical lesions, a primitive pathway like the pontomedullary reticular formation is an alternative pathway to recruit during stroke rehabilitation. This neuroplasticity process is initiated and maintained through stroke movement rehabilitation therapy, which involves repetitive functional movement attempts to create new neural connections or strengthen old, less used neural pathways for movement. To encourage daily functional movement to for upper limb motor recovery, the objective of the current study is to develop a computational neural network model to increase the feasibility of home movement analysis and classification of upper extremity functions in stroke patients. An enhanced probabilistic neural network trained to classify movement based on surface electromyographic signals will output predicted movement outcomes. A successful outcome of highly accurate, movement classification algorithm output can be applied to wearable devices for at-home monitoring of stroke patient motor recovery.