Size-Uniform 200 nm Particles: Fabrication and Application to Magnetofection

We report on the fabrication of arrays of mono- and multimetallic particles via metal evaporation onto lithographically patterned posts, as well as the magnetic force calibration and successful magnetofection of iron particles grown via this method. This work represents the first instance in which metal evaporation onto post structures was used for the formation of released, shape-defined metal particles. Also, our work represents the first use of lithographically defined particles as agents of magnetofection. Using these techniques it is possible to create particles with complex shapes and lateral dimensions as small as 40 nm. Our demonstrated compositionally flexible particles are highly size-uniform due to their photolithographically defined growth substrates, with particle dimensions along two axes fixed at 200 nm; the third axis dimension can be varied from 20 nm to 300 nm during the deposition procedure. Atomic percent of metals incorporated into the particle volume is highly tunable and particles have been synthesized with as many as four different metals. We performed magnetic force calibrations on a single particle size for iron particles using an axially magnetized NeFeB permanent magnet and comparisons are made with commercially available magnetic beads. In order to evalutate their usefulness as magnetofection agents, an antisense oligonucleotide (ODN) designed to correct the aberrant splicing of enhanced green fluorescent protein mRNA, was successfully transfected into a modified HeLa cell line. Magnetically enhanced gene delivery was accomplished in vitro using antisense ODN-laden iron particles followed by application of a field gradient. Magnetically enhanced transfection resulted in a 76% and 139% increase in fluorescence intensity when compared to Lipofectamine and antisense ODN-loaded particles delivered without magnetic treatment, respectively. To our knowledge, these experiments constitute the first use of lithographically defined particles as successful agents for magnetically enhanced transfection of an antisense oligonucleotide

Analysis of driven nanorod transport through a biopolymer matrix

Applying magnetic fields to guide and retain drug-loaded magnetic particles in vivo has been proposed as a way of treating illnesses. Largely, these efforts have been targeted at tumors. One significant barrier to long range transport within tumors is the extracellular matrix (ECM). We perform single particle measurements of 18 nm diameter nanorods undergoing magnetophoresis through ECM, and analyze the motion of these nanorods in two dimensions. We observe intra-particle magnetophoresis in this viscoelastic environment and measure the fraction of time these nanorods spend effectively hindered, versus effectively translating

Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution Brain-Machine Interface

We are developing methods of noninvasively delivering magnetic neuroparticles™ via intranasal administration followed by image-guided magnetic propulsion to selected locations in the brain. Once placed, the particles can activate neurons via vibrational motion or magnetoelectric stimulation. Similar particles might be used to read out neuronal electrical pulses via spintronic or liquid-crystal magnetic interactions, for fast bidirectional brain-machine interface. We have shown that particles containing liquid crystals can be read out with magnetic resonance imaging (MRI) using embedded magnetic nanoparticles and that the signal is visible even for voltages comparable to physiological characteristics. Such particles can be moved within the brain (e.g., across midline) without causing changes to neurological firing

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

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

Acoustic Propulsion of Nanorod Motors Inside Living Cells**

Abstract: The ultrasonic propulsion of rod-shaped nanomotors inside living HeLa cells is demonstrated. These nanomotors (gold rods about 300 nm in diameter and about 3 mm long) attach strongly to the external surface of the cells, and are readily internalized by incubation with the cells for periods longer than 24 h. Once inside the cells, the nanorod motors can be activated by resonant ultrasound operating at 4 MHz, and show axial propulsion as well as spinning. The intracellular propulsion does not involve chemical fuels or high-power ultrasound and the HeLa cells remain viable. Ultrasonic propulsion of nanomotors may thus provide a new tool for probing the response of living cells to internal mechanical excitation, for controllably manipulating intracellular organelles, and for biomedical applications

Mechanisms of Highly Efficient Photocatalytic Pollutant Degradation by Au/TiO2 Janus Nanoparticles

Semiconductor nanoparticles partially coated with metals have been widely used to degrade contaminants in water, but the physical mechanisms underlying degradation are poorly understood, limiting their real-world implementation. Here, we reveal the degradation mechanisms that dominate when gold-coated titanium dioxide (Au/TiO2) “Janus” nanoparticles (JNPs) are irradiated with monochromatic ultraviolet light (254 nm and 365 nm wavelengths) to degrade 1,4-dioxane, a carcinogenic model pollutant. To do so, we performed experiments with ultraviolet light at different wavelengths with and without radical quenching, extensive JNP characterization (SEM, XRD, EDS, DLS, and UV-Vis), and 3D simulations of self-propulsion and light-matter interactions. We traced the enhanced photocatalytic activity of Au-coated JNPs to both increased light absorption due to Au acting as an optical antenna, and inhibited recombination of photogenerated electrons and holes. These two effects increase the production of hydroxyl radicals, accelerating the degradation of 1,4-dioxane. The reduced electron/hole recombination is due to two factors: the Schottky barrier that forms between Au and TiO2 (which drives photogenerated electrons from TiO2 into the metal), and stoichiometric changes in the TiO2 that accompany gold sputtering which facilitate electron sequestration by the metal. In contrast, self-propulsion and surface plasmon resonance play at most a minor role

Nanocomposites of ferroelectric liquid crystals and FeCo nanoparticles: towards a magnetic response via the application of a small electric field

We study a nanocomposite consisting of a ferroelectric liquid crystal and a magnetic nanoparticle in order to explore the possibility of using it as a magnetic resonant imaging contrast agent which will measure a field of 20 V/m. To achieve this we use the ferroic properties exhibited by the nanocomposite. We used the ferroelectric liquid crystal 2-(4-((2-fluorooctyl)oxy)phenyl)-5-(octyloxy)pyrimidine mixed with FeCo nanoparticles nominally 2–3 nm in diameter in concentrations of 0.56, 4.3 and 10.8 wt%. The 10.8 wt% sample was chosen for our study because the nanoparticles acted as a lubricant for the ferroelectric liquid crystal. This concentration yields nanoparticle clusters in about 5 − 10 μm diameter spherulites. An electric field as low as 5V/cm is enough to turn and realign the spherulites where the particles are contained. We estimate the value of the magnetic in a spehrulite and associate it to the number of spherulites aligned as a function of electric field. We find thus that we can achieve low electric fields

Magnetically targeted delivery through cartilage

In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis