We present proof-of-concept experiments for developing a highly-sensitive and fast-response miniaturized single-walled carbon nanotube field-effect transistor (SWNT-FET) biosensor for electrically detecting adenovirus using ligand-receptor-protein specificity. SWNTs are mildly oxidized to form carboxylic groups on the surfaces without compromising the electronic integrity of the nanotubes. Then the human coxsackievirus and adenovirus receptor (CAR) is covalently functionalized onto the nanotube surface via diimide-activated amidation process. Upon exposure of the device to adenovirus protein, Ad12 Knob (Knob), specific binding of Knob to CAR decreases the current that flows through the SWNT-FET device. For control experiment, the CAR-SWNT device is exposed to YieF, which is a virus protein that does not bind specifically to CAR, and no current change is observed. The biological activity of the CAR and Knob proteins that are immobilized on SWNTs has been confirmed by previous fluorescence studies [1]. AFM analysis is done to show height increase of a few nanometers at specific spots where the CAR-Knob complex are covalently linked to the nanotube surface. Therefore, our results show that the human receptor protein CAR does immobilize on SWNT surface while fully retains its biological activity. Moreover, the specific binding of CAR to its complementary adenovirus Knob can be electrically detected using individual SWNT-FET devices. These findings suggest that CAR-functionalized SWNT-FETs can ably serve as biosensors for detection of environmental adenoviruses.

Neural prostheses often suffer from undesired chronic inflammatory tissue response. Therefore; a sensitive and real-time biosensor for inflammatory cytokine detection would provide invaluable information toward solving this problem. Such a biosensor based on an aptamer probe doped in polypyrrole and subsequent electrochemical impedance spectroscopy (EIS) has been developed. PDGF, an important inflammatory cytokine, has been successfully measured in both offline EIS characterization and real-time impedance monitoring. For in situ detection of PDGF, the best sensitivity of 10 ng/ml has been achieved.

A novel biomimetic route for the synthesis of conducting homopolymers and copolymers from aniline, phenol, pyrrole and 3,4-ethylenedioxy-thiophene in the presence of a polyelectrolyte, such as polystyrene sulfonate (SPS) is presented. A poly(ethylene glycol) modified hematin (PEG-Hematin) and the enzyme horseradish peroxidase (HRP) were used to catalyze the copolymerization of different monomers. UV-vis, FTIR, XPS, TGA and electrical conductivity studies for all complexes indicated the presence of a stable and electrically conductive form of these polymers. Furthermore, the presence of a polyelectrolyte, such as SPS, in this complex provides a unique combination of properties such as processability and water-solubility. Additionally catechins, the active compounds found in green tea, were polymerized and found to exhibit very interesting anti-carcinogenic properties. Here we report a unique enzymatic approach for the synthesis of water-soluble poly(catechins) with enhanced stability and potent anti-proliferative effects on human cancer cells in vitro. Various stereoisomers of catechin [(+), (-), (±)] and (-)-epicatechin have been biocatalytically polymerized using HRP in ethanol/buffer mixtures. This one-pot biocatalytic polymerization is carried out in ambient conditions yielding water-soluble poly(catechins). These synthesized poly(catechins) were tested for their growth inhibitory properties using a variety of normal and cancerous human epithelial cell lines. The poly(catechins) exhibit statistically significant greater growth inhibitory effects when compared to the monomers and exhibited specificity, inhibiting the growth of breast, colorectal and esophageal cancer cells while having little effect on normal epithelial cell growththus achieving a high therapeutic ratio. The synthesis, characterization and the growth inhibitory effects of these novel water-soluble poly(catechins) will also be presented.

Carbon nanotubes (CNTs) have attracted considerable attention as future field emission electron sources for a variety of applications due to their high aspect ratio and robust structure. One application is multi-pixel beam array x-ray micro-RT (radiotherapy) for small animal irradiation. The x-ray pixel beam array is produced by a CNT pixel cathode array. One challenge in the micro-RT fabrication is how to fabricate individually addressable multi-pixel CNT cathode array on wafer with high pixel beam packing density and high emission current. We report here the development of a new CNT field emission multi-pixel cathode array chip, a vital component of the multi-pixel beam x-ray micro-RT system under development. The CNT field emission cathode array has up to 25 (5 × 5) individually addressable cathode pixels, each is 1 mm in diameter and with center-to-center distance of 2 mm. The fabrication is a two-step process: first a Cr/Cu electrical contact was fabricated on Si substrates with a 5 μm SiO2 dielectric layer using photolithography; and second the CNTs were selectively deposited on 1 mm-diameter predefined Cr/Cu contact dots by using a combined photolithography/electrophotoresis technique. The electron pixel beams produced from the multi-pixel arrays are uniform and individually controllable and can be used for micro-RT application.

Various formulations of polymeric hydrogels were synthesized and evaluated with the goal of developing a novel skin-surface biopotential electrode. Materials explored within the study included poly(2-hydroxyethyl methacrylate) (polyHEMA) in pure form or impregnated with the conducting polymers polypyrrole or poly(3,4-ethylenedioxythiophene) (PEDOT), as well as polyacrylate. The drying dynamics, ionic conductivity, and impedance of the prototype materials were characterized when applied to porcine and human skin, in order to determine their utility for a minimum preparation and low specific impedance surface electrode. The addition of a fraction of PEDOT or polypyrrole within a polyHEMA gel was found to decrease hydrogel impedance when tested within PBS, as well as on non-abraded porcine skin. A polyacrylate component added to polyHEMA had no significant effect on hydrogel impedance in PBS, but significantly reduced impedance on the porcine skin surface. Although having much lower specific impedance (impedance normalized by the contact area) than the commercial skin surface electrode (3M Red Dot), polyHEMA based electrodes require skin abrasion. Pure cross-linked polyacrylate gel was found to provide the most attractive option, and yielded competitive low-impedance performance on non-abraded human skin.

In this work chemical functionalization of carbon nanotubes was conducted with the aim of improving their ability to be integrated into biological systems. Functionalized SWNT demonstrated to be an excellent vehicle to translocate a highly conjugated organic fluorophore across the cell membrane while causing little toxicity to the cells. Functionalized SWNT were introduced into different lines of the primary brain tumor cells Glioblastoma Multiforme (GBM). Once within the cell interior, the optical properties of the SWNT were used for both fluorescent imaging characterization and selective killing of tumor cells that had exhibited high SWNT uptake levels upon exposure to NIR radiation. Propidium iodide (PI) was employed as an indicator to determine the number of cells with compromised plasma membrane. Cell surviving ratio of as little as 10-20 percent were found in samples with intracellular nanotubes exposed to NIR radiation while a cell surviving ratio of about 95 percent was typical in irradiated samples without intracellular nanotubes. Control samples showed cell surviving ratios comparable to exposed samples without intracellular nanotubes. This study reveals new insights upon the influence of SWNT optical properties in the physicochemical processes within cells and how they can be used to develope therapy for cancerous brain tumors.

Encapsulation of PC12 cells (neural cell model) in alginate hydrogels with a protective coating of poly(lactic-co-glycolic acid) (PLGA) was achieved in the present study using co-axial electrospinning. Co-axial electrospinning consists of two concentric capillaries compared to only one capillary in conventional electrospinning. This allows for the processing of two liquid solutions simultaneously. Neural cells suspended in hydrogels were injected in the inner capillary, while the carbon nanotubes (added for conductivity) suspended in PLGA were injected in the outer capillary at controlled flow rates. On the application of a high voltage, a compound jet formed at the capillary exits and resulted in a co-electrospun fiber of nerve cells encapsulated in PLGA with carbon nanotubes. Carbon nanotubes were included to make the outer shell conductive to stimulate the PC12 cells. In this study, the voltage varied from 0 to 15 kV and various flow rates were tested to achieve a stable cone-jet mode in electrospinning. The cell density in the media varied from 0.5 to5 million cells/ml and the polymer solution (PLGA) concentration varied from 1 to 10 mg/ml. This resulted in a three dimensional conductive scaffold with nano-features (due to carbon nanotubes) on the polymer surface, which were collected on the grounded substrate. PC12 cells were found to be viable inside microspheres after 3 days. The size of the microspheres was quite uniform and less than 200 μm. This technique may be very useful for the development of cell encapsulated scaffolds which mimic natural body tissue organization for tissue engineering applications such as nervous system regeneration.