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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Modeling Lysis Dynamcis Of Pore Forming Toxins And Determination Of Mechanical Properties Of Soft Materials

Vaidyanathan, M S 11 1900 (has links) (PDF)
Pore forming toxins are known for their ability to efficiently form transmembrane pores which eventually leads to cell lysis. PFTs have potential applications in devel-oping novel drug and gene delivery strategies. Although structural aspects of many pore forming toxins have been studied, very little is known about the dynamics and subsequent rupture mechanisms. In the first part of the thesis, a combined experimental and modeling study to understand the lytic action of Cytolysin A (ClyA) toxins on red blood cells (RBCs) has been presented. Lysis experiments are carried out on a 1% suspension of RBCs for different initial toxin concentrations ranging from 100 – 500 ng/ml and the extent of lysis is monitored spectrophotometrically. Using a mean field approach, we propose a non – equilibrium adsorption-reaction model to quantify the rate of pore formation on the cell surface. By analysing the model in a pre-lysis regime, the number of pores per RBC to initiate rupture was found to lie between 400 and 800. The time constants for pore formation are estimated to lie between 1-25 s and monomer conformation time scales were found to be 2-4 times greater than the oligomerization times. Using this model, we are able to predict the extent of cell lysis as a function of the initial toxin concentration. Various kinetic models for oligomerization mechanism have been explored. Irreversible sequential kinetic model has the best agreement with the available experimental data. Subsequent to the mean field approach, a population balance model was also formulated. The mechanics of cell rupture due to pore formation is poorly understood. Efforts to address this issue are concerned with understanding the changes in the membrane mechanical properties such as the modulus and tension in the presence of pores. The second part of the thesis is concerned with using atomic force microscopy to measure the mechanical properties of cells. We explore the possibility of employing tapping mode AFM (TM-AFM) to obtain the elastic modulus of soft samples. The dynamics of TM-AFM is modelled to predict the elastic modulus of soft samples, and predict optimal cantilever stiffness for soft biological samples. From experiments using TM-AFM on Nylon-6,6 the elastic modulus is predicted to lie between 2 and 5 GPa. For materials having elastic moduli in the range of 1– 20 GPa, the cantilever stiffness from simulations is found to lie in the range of 1 – 50 N/m. For soft biological samples, whose elastic moduli are in the range of 10-1000 kPa, a narrower range of cantilever stiffness (0.1 – 0.6 N/m), should be used.
12

Thermal Characterization of Heated Microcantilevers and a Study on Near-Field Radiation

Park, Keunhan 05 April 2007 (has links)
Recently, remarkable advances have been made in the understanding of micro/nanoscale energy transport, opening new opportunities in various areas such as thermal management, data storage, and energy conversion. This dissertation focuses on thermally-sensed nanotopography using a heated silicon microcantilever and near-field thermophotovoltaic (TPV) energy conversion system. A heated microcantilever is a functionalized atomic force microscope (AFM) cantilever that has a small resistive heater integrated at the free end. Besides its capability of increasing the heater temperature over 1,000 K, the resistance of a heated cantilever is a very sensitive function of temperature, suggesting that the heated cantilever can be used as a highly sensitive thermal metrology tool. The first part of the dissertation discusses the thermal characterization of the heated microcantilever for its usage as a thermal sensor in various conditions. Particularly, the use of heated cantilevers for tapping-mode topography imaging will be presented, along with the recent experimental results on the thermal interaction between the cantilever and substrate. In the second part of the dissertation, the so-called near-field TPV device is introduced. This new type of energy conversion system utilizes the significant enhancement of radiative energy transport due to photon tunneling and surface polaritons. Investigation of surface and bulk polaritons in a multilayered structure reveals that radiative properties are significantly affected by polariton excitations. The dissertation then addresses the rigorous performance analysis of the near-field TPV system and a novel design of a near-field TPV device.

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