We present the development of a new imaging technique for the early diagnosis of hepatocellular carcinoma that utilizes surface-modified gold nanoparticles in combination with x-ray imaging. Tissues labeled with these electron-dense particles show enhanced x-ray scattering over normal tissues, distinguishing cells containing gold nanoparticles from cells without gold in x-ray scatter images. Our results suggest that this novel approach could enable the in vivo detection of tumors as small as a few millimeters in size.

Guidance of neuronal extensions is a complex process essential for linking neurons into complex functional networks underlying the workings of the neural system. Decades of research have suggested the ability of neuronal growth cones to integrate multiple types of cues during the extension process, but also have raised numerous still unanswered questions about synergy or antagonism between the superimposed chemical and mechanical signaling inputs. In this study, using a novel microfabricated analysis platform, we investigate the response of primary mouse embryonic hippocampal neurons to superimposed topographic and soluble chemical cues. We find that an optimal spatial frequency of topographic cues exists, maximizing the precision of the neurite extension. This optimal frequency can help the extending neurites navigate a topographically complex environment, providing pronounced directional selectivity. We also demonstrate that this cue can synergistically enhance attractive and suppress repulsive guidance by the bi-functional soluble cue Netrin-1, and eliminate the repulsive guidance by a chemorepellent Semaphorin3A (Sema3A). These results suggest that topographic cues can provide optimal periodic input into the guidance signaling processes involved in growth cone chemoattraction and can synergistically interact with chemical gradients of soluble guidance cues, shedding light on complex events accompanying the development of the functional nervous system.

In the vascular niche, the extracellular matrix (ECM) provides a structural scaffold with a rich ligand landscape of essential matrix proteins that supports the organization and stabilization of endothelial cells (ECs) into functional blood vessels. Many of the physical interactions between ECs and macromolecular components of the ECM occur at both the micron and sub-micron scale. In addition, the elasticity of the ECM has been shown to be a critical factor in the progress of the angiogenic cascade. Here we sought to determine the effect of substrate topography and elasticity (stiffness) on EC behavior. Utilizing a unique SiO2 substrate with an array of micropillars, we first demonstrate that micropillars with heights >3 μm significantly decrease EC adhesion and spreading. Fibronectin (Fn) patterning onf 1 μm high micropillars enabled EC adhesion onto the micropillars and promoted alignment in a single-cell chain manner. We then developed a robust method to generate a soft micropillar substrate array made of polydimethylsiloxane (PDMS), similar to the SiO2 substrate. Finally, we examined the kinetics of EC adhesion and spreading on the soft PDMS substrates compared to the stiff SiO2 substrates. Cell culturing on the PDMS substrates demonstrated an enhanced EC elongation and alignment when compared to stiff SiO2 with similar topographical features. We conclude that the elongation and alignment of ECs is co-regulated by substrate topography and stiffness and can be harnessed to guide vascular organization.

The electrochemistry of 50 μm diameter Pt electrodes used for neural stimulation was studied in vitro by reciprocal derivative chronopotentiometry. This differential method provides well-defined electrochemical signatures of the various polarization phenomena that occur at Pt microelectrodes and are generally obscured in voltage transients. In combination with a novel in situ coulometric approach, irreversible H(2) and O(2) evolution, Pt dissolution and reduction of dissolved O(2) were detected. Measurements were performed with biphasic, charge-balanced, cathodic-first and anodic-first current pulses at charge densities ranging from 0.07 to 1.41 mC/cm(2) (real surface area) in phosphate buffered saline (PBS) with and without bovine serum albumin (BSA). The extent to which O(2) reduction occurs under the different stimulation conditions was compared in O(2)-saturated and deoxygenated PBS. Adsorption of BSA inhibited Pt dissolution as well as Pt oxidation and oxide reduction by blocking reactive sites on the electrode surface. This inhibitory effect promoted the onset of irreversible H(2) and O(2) evolution, which occurred at lower charge densities than those in PBS. Reduction of dissolved O(2) on Pt electrodes accounted for 19-34% of the total injected charge in O(2)-saturated PBS, while a contribution of 0.4-12% was estimated for in vivo stimulation. These result may prove important for the interpretation of histological damage induced by neural stimulation and therefore help define safer operational limits.

No abstract

The reliable integration of carbon nanotube (CNT) electrodes in future neural probes requires a proper embedding of the CNTs to prevent damage and toxic contamination during fabrication and also to preserve their mechanical integrity during implantation. Here we describe a novel bottom-up embedding approach where the CNT microelectrodes are encased in SiO(2) and Parylene C with lithographically defined electrode openings. Vertically aligned CNTs are grown on microelectrode arrays using low-temperature plasma-enhanced chemical vapor deposition compatible with wafer-scale CMOS processing. Electrodes with 5, 10, and 25 μm diameter are realized. The CNT electrodes are characterized by electrochemical impedance spectroscopy and cyclic voltammetry and compared against cofabricated Pt and TiN electrodes. The superior performance of the CNTs in terms of impedance (≤4.8 ± 0.3 kΩ at 1 kHz) and charge-storage capacity (≥513.9 ± 61.6 mC/cm(2)) is attributed to an increased wettability caused by the removal of the SiO(2) embedding in buffered hydrofluoric acid. Infrared spectroscopy reveals an unaltered chemical fingerprint of the CNTs after fabrication. Impedance monitoring during biphasic current pulsing with increasing amplitudes provides clear evidence of the onset of gas evolution at CNT electrodes. Stimulation is accordingly considered safe for charge densities ≤40.7 mC/cm(2). In addition, prolonged stimulation with 5000 biphasic current pulses at 8.1, 40.7, and 81.5 mC/cm(2) increases the CNT electrode impedance at 1 kHz only by 5.5, 1.2, and 12.1%, respectively. Finally, insertion of CNT electrodes with and without embedding into rat brains demonstrates that embedded CNTs are mechanically more stable than non-embedded CNTs.

No abstract

Here we describe an acid rain neutralization laboratory experiment and its corresponding instructional video. This experiment has been developed and implemented for use in the teaching laboratory of a large introductory chemistry course at Brown University. It provides a contextually relevant example to introduce beginner-level students with little or no acid–base chemistry background to the basic theories of solution chemistry. First, students measure the conductivity of water samples with different ionic compositions, serving as an introduction to the conductivity of solutions. Second, to simulate the neutralization reaction between acid rain and limestone as it occurs in nature, students pass a sulfuric acid solution through a column containing calcium carbonate and monitor the conductivity of the resulting solution. Students are then required to graph conductivity versus volume of sulfuric acid added to the calcium carbonate column and use the resulting plot to calculate the equivalence point. Additionally, an instructional video containing animated features was created and utilized to engage students in learning new chemistry concepts by relating chemistry to their daily lives and helping them visualize experimental setups. Significantly, the experiment has been adapted to include the use of a pH probe or multimeter to make it more accessible to K–12 classrooms and teaching laboratories without access to conductivity probes.