Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation.

Extracellular electrical stimulation (ES) can provide electrical potential from outside the cell membrane, but it is often ineffective due to interference from external factors such as culture medium resistance and membrane capacitance. To address this, we developed a vertical nanowire electrode array (VNEA) to directly provide intracellular electrical potential and current to cells through nanoelectrodes. Using this approach, the cell membrane resistivity and capacitance could be excluded, allowing effective ES. Human fetal neural stem cells (hfNSCs) were cultured on the VNEA for intracellular ES. Combining the structural properties of VNEA and VNEA-mediated ES, transient nanoscale perforation of the electrode was induced, promoting cell penetration and delivering current to the cell. Intracellular ES using VNEA improved the neuronal differentiation of hfNSCs more effectively than extracellular ES and facilitated electrophysiological functional maturation of hfNSCs because of the enhanced voltage-dependent ion-channel activity. The results demonstrate that VNEA with advanced nanoelectrodes serves as a highly effective culture and stimulation platform for stem-cell neurogenesis.

Disaggregation of Amyloid-ß Plaques by a Local Electric Field Generated by a Vertical Nanowire Electrode Array.

The aggregation and accumulation of amyloid-ß (Aß) peptides is a characteristic pathology for Alzheimer's disease (AD). Although noninvasive therapies involving stimulation by electric field (EF) have been reported, the efficiency of Aß disaggregation needs to be further improved for this strategy to be used in clinical settings. In this study, we show that an electrode based on a vertical nanowire electrode array (VNEA) is far more superior to a typical flat-type electrode in disaggregating Aß plaques. The enhanced disaggregation efficiency of VNEA is due to the formation of high-strength local EF between the nanowires, as verified by in silico and empirical evidence. Compared with those of the flat electrode, the simulation data revealed that 19.8-fold and 8.8-fold higher EFs are generated above and between the nanowires, respectively. Moreover, empirical cyclic voltammetry data demonstrated that VNEA had a 2.7-fold higher charge capacity than the flat electrode; this is associated with the higher surface area of VNEA. The conformational transition of Aß peptides between the ß-sheet and α-helix could be sensitively monitored in real time by the newly designed in situ circular dichroism instrument. This highly efficient EF-configuration of VNEA will lower the stimulation power for disaggregating the Aß plaques, compared to that of other existing field-mediated modulation systems. Considering the complementary metal-oxide-semiconductor-compatibility and biocompatible strength of the EF for perturbing the Aß aggregation, our study could pave the way for the potential use of electric stimulation devices for in vivo therapeutic application as well as scientific studies for AD.

Long-term Intracellular Recording of Optogenetically-induced Electrical Activities using Vertical Nanowire Multi Electrode Array.

Continuous recording of intracellular activities in single cells is required for deciphering rare, dynamic and heterogeneous cell responses, which are missed by population or brief single-cell recording. Even if the field of intracellular recording is constantly proceeding, several technical challenges are still remained to conquer this important approach. Here, we demonstrate long-term intracellular recording by combining a vertical nanowire multi electrode array (VNMEA) with optogenetic stimulation to minimally disrupt cell survival and functions during intracellular access and measurement. We synthesized small-diameter and high-aspect-ratio silicon nanowires to spontaneously penetrate into single cells, and used light to modulate the cell's responsiveness. The light-induced intra- and extracellular activities of individual optogenetically-modified cells were measured simultaneously, and each cell showed distinctly different measurement characteristics according to the cell-electrode configuration. Intracellular recordings were achieved continuously and reliably without signal interference and attenuation over 24 hours. The integration of two controllable techniques, vertically grown nanowire electrodes and optogenetics, expands the strategies for discovering the mechanisms for crucial physiological and dynamic processes in various types of cells.

Nanoelectrode-mediated single neuron activation.

Elucidating cellular dynamics at the level of a single neuron and its associated role within neuronal circuits is essential for interpreting the complex nature of the brain. To investigate the operation of neural activity within its network, it is necessary to precisely manipulate the activation of each neuron and verify its propagation path via the synaptic connection. In this study, by exploiting the intrinsic physical and electrical advantages of a nanoelectrode, a vertical nanowire multi electrode array (VNMEA) is developed as a neuronal activation platform presenting the spatially confined effect on the intracellular space of individual cells. VNMEA makes a distinct difference between the interior and exterior cell potential and the current density, deriving the superior effects on activating Ca2+ responses compared to extracellular methods under the same conditions, with about 2.9-fold higher amplitude of Ca2+ elevation and a 2.6-fold faster recovery rate. Moreover, the synchronized propagation of evoked activities is shown in connected neurons implying cell-to-cell communications following the intracellular stimulation. The simulation and experimental consequences prove the outstanding property of temporal/spatial confinement of VNMEA-mediated intracellular stimulation to activate a single neuron and show its potential in localizing spiking neurons within neuronal populations, which may be utilized to reveal the connection and activation modalities of neural networks.

Plasma-Doped Si Nanosheets for Transistor and p-n Junction Application.

Since the discovery of graphene, layered transition metal dichalcogenides (TMDs) have been considered promising materials for applications in various fields because of their fascinating structural features and physical properties. Doping in semiconducting TMDs is essential for their practical application. In this regard, two-dimensional (2D) Si materials have emerged as a key component of 2D electronic, optics, sensing, and spintronic devices because of their complementary metal-oxide-semiconductor (CMOS) compatibility, high-quality oxide formation, moderated bandgap, and well-established doping techniques. Here, we report the tuning of the electronic properties of Si nanosheets (NSs) using a plasma-doping technique. Using this doping process, we fabricated p-n homojunction diodes and transistors with Si NSs. The estimated high ON/OFF ratio of ∼106 and field-effect hole mobility of 329 cm2 V-1 s-1 suggest a high crystal quality of the Si NSs. We also demonstrate vertically stacked heterostructured p-n junction diodes with MoS2, which exhibit rectifying properties and excellent light response.

5-demethylovalicin, as a methionine aminopeptidase-2 inhibitor produced by Chrysosporium.

5-Demethylovalicin was isolated from the fermentation broth Chrysosporium lucknowense and the structure was identified by spectroscopic methods. 5-Demethylovalicin inhibited the recombinant human MetAP-2 (IC(50)=17.7 nM) and the growth of human umbilical vein endothelial cells (HUVEC; IC(50)=100 nM) in cell proliferation assay without cytotoxicity on the transformed and cancer cell lines.