Fabrication and Manipulation of Micro- and Nano-Scale Magnetic Particles: Application to Magnetofection, Nanopositioning, and Drug Delivery

Abstract

Magnetic particles offer scientists a unique opportunity – the ability to apply forces to these particles from a distance by means of a magnetic field gradient. This property becomes increasingly useful for probing and prodding physical processes in the biological world. Because a large fraction of biological materials are nonmagnetic we are able apply forces to the particles which are not felt by the biological samples, unless of course the biomaterials are in some way mechanically coupled to the magnetic particles. This dissertation describes two techniques for creating shapedefined and compositionally flexible magnetic micro/nanoparticles. Both techniques fall into the category of top-down synthesis, making use of templates to pattern and grow particles. The first technique relies on thermal evaporation of metals onto pre-patterned wafers, the resulting metal deposition creating clusters of material atop lithographically defined posts. The technique produces shape-defined particles and allows for user-defined particle composition (resulting materials named Post-Particles). The second technique relies on electrodeposition into the pores of anodized aluminum oxide templates and results in aspect ratio-adjustable magnetic rods with a wide range of diameters. Here I use the technique to create novel nickel-gold Janus nanorods. In this dissertation I apply particles created using these techniques to three different biological scenarios. First, I demonstrate the process of enhanced oligonucleotide delivery to cells in vitro using magnetic Post-Particles delivered to cells in an applied magnetic field gradient. Next, high aspect ratio Janus rods are implemented as rotational swimmers capable of cargo and single cell manipulation in microfluidic settings. Finally, magnetic nanorods are applied to the process of nanoparticle transport through protein-rich gels and their motion is quantified on a single-particle basis. This final experiment is designed to inform the community of researchers interested in magnetic drug targeting as to the forces experienced by and types of motion demonstrated by rod-shaped nanoparticles moving through extracellular matrix, the primary barrier to long-range nanoparticle distribution in localized cancer tumors. This chapter presents the first data on non-continuous motion (moving in fits-and-starts) of small particles undergoing magnetophoresis through the extracellular matrix, and offers this data in direct contrast with continuous motion of large particles through the same material.Doctor of Philosoph

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