Magnetic manipulation and electrical interrogation of individual cells using nanomaterials

The engineering of abiotic nanoscale materials has propelled them into niche biomedical applications. Generally, two traits suit them for interaction with biological species: their size scale allows access to intricate cellular machinery, and they can be conveniently modified with biochemical cues that are recognized by the cell. In particular, the negligible response of biological tissues to magnetic fields facilitates the use of magnetic nanoparticles for noninvasive cellular manipulation. Furthermore, unique electrical and mechanical properties of carbon nanotubes suit them for the interrogation of electrically excitable cells. This dissertation presents the design, fabrication, and testing of functional cellular interfaces using magnetic nanowires and carbon nanotubes.;In Part 1, we demonstrated three versatile uses of magnetic nanowires. The first study describes the fabrication of 200-nm-diameter 20- to 40-microm-long nickel nanowires by electrodeposition. Scanning electron microscopy and confocal fluorescence microscopy verified that these nanowires, coated in serum proteins, were internalized by B35 neuronal neuroblasts in vitro. Uptake of nanowires was initiated within 40 min. A 20-mT magnetic field was then applied to transport and position the neurons relative to lithographically patterned magnetic microstructures. The second study explored therapeutic uses of the nanowires for hyperthermia. Cultures of HEK-293 kidney cells were exposed to nickel nanowires and a 810-MHz electromagnetic field to cause death in cells proximal to the nanowires. The third study explored the induction of death in 3T3 fibroblasts by magnetomotive actuation of internalized 4-microm nanowires. The internalization of the nanowires alone, verified by confocal microscopy, did not upregulate the cytokine, interleukin-6. The nanowires were subsequently actuated with a 240-mT magnetic field rotating at 1-Hz. Actuation for 20 min caused a 89% reduction in the viability of the fibroblast cultures.;Part 2 of this dissertation presents the implementation of carbon nanotubes to enhance microelectrodes for cellular recording. Microelectrodes of geometric surface areas from 20 to 200 microm2 were designed, fabricated, and characterized by Raman spectroscopy and electrochemical techniques. Compared to planar gold surfaces, randomly oriented nanotubes deposited by chemical vapor deposition achieved 16x to 20x reduction in the overall electrode impedance at 1 kHz. Cyclic voltammetry in potassium ferricyanide showed potential-peak separations of 133 mV and 198 mV for gold- and carbon-nanotubes electrodes, respectively. It was demonstrated that vertically aligned nanotubes deposited by plasma-enhanced chemical vapor deposition penetrated the membrane of an overlaying culture of neonatal-rat ventricular myocytes. The miniaturization and cellular interfacing enable by these nanotube electrodes may enable new tools for cardiologists to study the cellular mechanisms of arrhythmia. The studies presented in this work demonstrate the versatility of two emerging nanotechnologies in biomedical engineering.