Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection
Abstract
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Shock waves have potential applications in many areas such as in geology, seismological techniques, and biomedical applications. Specifically in biomedical field, shock waves can be used to permeabilize cells, allowing a wide variety of particles to penetrate the cell membrane for gene therapy or drug delivery applications. Recently, nanothermite composition consisting of fuel and oxidizer nanoparticles was shown to propagate at velocities in the same range as the heavy-metal azides including metallic azides and fulminates, however, the destructive forces associated with the later materials is not exhibited. Large range of tunability can be achieved by modifying the nanothermite compositions by adding polymers or other nanoscale energetic materials. Also, these nanothermites can be integrated with MEMS based systems owing to their low critical combustion diameters and high energy densities. The present research describes the characterization of different nanothermite composites and the fabrication of a shockwave reaction actuator incorporating MEMS based micro-devices. The actuator was specifically designed for experimenting with biological samples and testing particle delivery and transfection capability which are key aspects in gene therapy. Each actuator component was first characterized to study its effect on the shockwave generation and propagation. The actuator demonstrates the delivery of 59 to 77 kDa FITC-Dextran into chicken cardiomyocytes with cytoplasmic delivery efficiency greater than 90 %, maximum intranuclear delivery efficiency of 84 %, and cell survival rates exceeding 95 % in minimum operating pressure conditions. In addition to the superior delivery efficiencies and cell survival, the results also indicate the ability to control the level of particle delivery. Tunable nanothermite reactions enable versatile pressure generating characteristics which can extend the technology to a spectrum of molecular delivery applications.
Degree
Ph. D.
Thesis Department
Rights
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