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- All Subjects: Biophysics
Description
One major issue that surgeons face during closed body cavity surgery is fogging of the lens surfaces. The cloudy and opaque lens surface caused by water vapor present in closed body cavities forces the surgeon to repeatedly remove the endoscope, wipe it, and reinsert it back into the patient. This presents several risks such as increased surgery time, greater scarring, and an increased chance of infection. In order to address this issue, the development of the Thin Fluid Film Device (TFFD™) VitreOx™ aims to render the lens surface hydrophilic, whereas it is typically hydrophobic. By creating a hydrophilic polymeric nanomesh, the 3-D water droplets can be trapped to lie flatter, thus resulting in a flatter 2-D sheeting effect. The light can no longer be refracted at different angles off of the 3-dimensional water beads, thus eliminating the opacity of the lens surface.
Two animal trials were performed involving a rat and two pigs in order to prove the efficacy of VitreOx™ in addition to being compared with competitor, Covidien Clearify. A laparoscopy was performed on each animal, and the length of time that the endoscope took to fog was measured post product application. The results of the optimized animal clinical trials involving two Yucatan pigs showed that the scope treated with Covidien’s Clearify began fogging within 8 minutes and continued to do so for the remained of the surgery, as opposed to the scope with VitreOx™ which remained fog free for the full 90-minute procedure. The results proved the efficacy of our product.
The second part of the thesis aimed to optimize HemoClear™, the blood evacuating TFFD™. This was done by testing a higher concentration of 6 mg/mL fibrinogen as compared to previous work. After conducting an experiment designed to mimic closed-body cavity surgery it was determined that the HemoClear™ eliminated fog 67% of the time and evacuated blood with a success of 83%. Future work aims to continue testing at this concentration with variances in mixing and application technique.
Two animal trials were performed involving a rat and two pigs in order to prove the efficacy of VitreOx™ in addition to being compared with competitor, Covidien Clearify. A laparoscopy was performed on each animal, and the length of time that the endoscope took to fog was measured post product application. The results of the optimized animal clinical trials involving two Yucatan pigs showed that the scope treated with Covidien’s Clearify began fogging within 8 minutes and continued to do so for the remained of the surgery, as opposed to the scope with VitreOx™ which remained fog free for the full 90-minute procedure. The results proved the efficacy of our product.
The second part of the thesis aimed to optimize HemoClear™, the blood evacuating TFFD™. This was done by testing a higher concentration of 6 mg/mL fibrinogen as compared to previous work. After conducting an experiment designed to mimic closed-body cavity surgery it was determined that the HemoClear™ eliminated fog 67% of the time and evacuated blood with a success of 83%. Future work aims to continue testing at this concentration with variances in mixing and application technique.
ContributorsSinha, Saloni Agarwal (Author) / Culbertson, Robert (Thesis director) / Herbots, Nicole (Committee member) / Watson, Clarizza (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Exploring Structure and Function of Human Cold Sensing Protein TRPM8 with ROSETTA Comparative Models
Description
Transient Receptor Potential (TRP) channels are a diverse class of ion channels notable as polymodal sensors. TRPM8 is a TRP channel implicated in cold sensation, nociception, and a variety of human diseases, including obesity and cancer. Despite sustained interest in TRPM8 since its discovery in 2001, many of the molecular mechanisms that underlie function are not yet clear. Knowledge of these properties could have implications for medicine and physiological understanding of sensation and signaling. Structures of TRP channels have proven challenging to solve, but recent Cryoelectron microscopy (Cryo-EM) structures of TRPV1 provide a basis for homology-based modeling of TRP channel structures and interactions. I present an ensemble of 11,000 Rosetta computational homology models of TRPM8 based on the recent Cryo-EM apo structure of TRPV1 (PDB code:3J5P). Site-directed mutagenesis has provided clues about which residues are most essential for modulatory ligands to bind, so the models presented provide a platform to investigate the structural basis of TRPM8 ligand modulation complementary to existing functional and structural information. Menthol and icilin appear to interact with interfacial residues in the sensor domain (S1-S4). One consensus feature of these sites is the presence of local contacts to the S4 helix, suggesting this helix may be mechanistically involved with the opening of the pore. Phosphatidylinositol 4,5-bisphosphate (PIP2)has long been known to interact with the C-terminus of TRPM8, and some of the homology models contain plausible binding pockets where PIP2 can come into contact with charged residues known to be essential for PIP2 modulation. Future in silico binding experiments could provide testable hypothesis for in vitro structural studies, and experimental data (e.g. distance constraints from electron paramagnetic resonance spectroscopy [EPR]) could further refine the models.
ContributorsHelsell, Cole Vincent Maher (Author) / Van Horn, Wade (Thesis director) / Wang, Xu (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
The response of living cells to electric field (EF) has been observed for more than a hundred years, but the mechanism of how cells interact with EF is not entirely ascertained. Although many efforts have been devoted to the application of EF stimulation in tissue engineering and regeneration, the fundamental scientific principle of such practice remains unveiled and keeps drawing attention during the pursuit of consistent outcomes. In this regard, my research focuses on the underlying mechanism by which EF stimulation evokes cellular responses and the EF modulation of cell signaling pathways to physiological behaviors. The first part of my research focuses on developing the platform for controlled EF stimulation and real-time imaging/analysis. High-k dielectric passivated microelectrodes are fabricated to send capacitively coupled alternating current electric field (AC EF) stimulation to cells. I have developed two generations of EF stimulation devices with environmental control chambers: the first one is used to study cell signaling pathway dynamics; the second one is upgraded with long-term culture capability to study cell physiological behaviors. The second part of my research focuses on the quantification and mechanistic study of AC EF perturbation of the extracellular signal-related kinase (ERK) signaling pathway. I demonstrate that AC EF stimulation can induce both inhibition and activation of the ERK pathway, with different AC EF amplitude thresholds and time and magnitude scales. The mechanistic study shows that the ERK activation is initiated by AC EF-induced epidermal growth factor receptor (EGFR) phosphorylation, and the ERK inhibition is related to AC EF-induced change of Ras activities. In addition, these ERK responses show high sensitivity to AC EF waveform and timing, indicating electrostatic coupling mechanism and providing new parameter spaces for further investigation on the modulation of the ERK signaling pathway via AC EF stimulation. The last part of my research steers to cell physiological behaviors under prolonged AC EF stimulation. I report that AC EF stimulation can clearly inhibit cell proliferation and migration, and the inhibition in cell proliferation is sensitive to AC EF amplitude, stimulation pattern, and pulse rising time. These findings can benefit the AC EF application in medical treatment.
ContributorsHu, Minxi (Author) / Qing, Quan (Thesis advisor) / Lindsay, Stuart (Committee member) / Guo, Jia (Committee member) / Arizona State University (Publisher)
Created2023