Scalable Thousand Channel Penetrating Microneedle Arrays on Flex for Multimodal and Large Area Coverage BrainMachine Interfaces.

The Utah array powers cutting-edge projects for restoration of neurological function, such as BrainGate, but the underlying electrode technology has itself advanced little in the last three decades. Here, advanced dual-side lithographic microfabrication processes is exploited to demonstrate a 1024-channel penetrating silicon microneedle array (SiMNA) that is scalable in its recording capabilities and cortical coverage and is suitable for clinical translation. The SiMNA is the first penetrating microneedle array with a flexible backing that affords compliancy to brain movements. In addition, the SiMNA is optically transparent permitting simultaneous optical and electrophysiological interrogation of neuronal activity. The SiMNA is used to demonstrate reliable recordings of spontaneous and evoked field potentials and of single unit activity in chronically implanted mice for up to 196 days in response to optogenetic and to whisker air-puff stimuli. Significantly, the 1024-channel SiMNA establishes detailed spatiotemporal mapping of broadband brain activity in rats. This novel scalable and biocompatible SiMNA with its multimodal capability and sensitivity to broadband brain activity will accelerate the progress in fundamental neurophysiological investigations and establishes a new milestone for penetrating and large area coverage microelectrode arrays for brain-machine interfaces.

Intrinsically Linear Transistor for Millimeter-Wave Low Noise Amplifiers.

Transistors are the backbone of any electronic and telecommunication system but all known transistors are intrinsically nonlinear introducing signal distortion. Here, we demonstrate a novel transistor with the best linearity achieved to date, attained by sequential turn-on of multiple channels composed of a planar top-gate and several trigate Fin field-effect transistors (FETs), using AlGaN/GaN structures. A highly linearized transconductance plateau of >6 V resulted in a record linearity figure of merit OIP3/PDC of 15.9 dB at 5 GHz and a reduced third-order intermodulation power by 400× in reference to a conventional planar device. The proposed architecture also features an exceptional performance at 30 GHz with an OIP3/PDC of ≥8.2 dB and a minimum noise figure of 2.2 dB. The device demonstrated on a scalable Si substrate paves the way for GaN low noise amplifiers (LNAs) to be utilized in telecommunication systems, and is also translatable to other material systems.

Selective Formation of Porous Pt Nanorods for Highly Electrochemically Efficient Neural Electrode Interfaces.

The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility in scalable and human-compatible implantable neural interfaces can significantly advance the performance of clinical and research electrodes. We utilize low-temperature selective dealloying to develop scalable and biocompatible one-dimensional platinum nanorod (PtNR) arrays that exhibit superb electrochemical properties at various length scales, stability, and biocompatibility for high performance neurotechnologies. PtNR arrays record brain activity with cellular resolution from the cortical surfaces in birds and nonhuman primates. Significantly, strong modulation of surface recorded single unit activity by auditory stimuli is demonstrated in European Starling birds as well as the modulation of local field potentials in the visual cortex by light stimuli in a nonhuman primate and responses to electrical stimulation in mice. PtNRs record behaviorally and physiologically relevant neuronal dynamics from the surface of the brain with high spatiotemporal resolution, which paves the way for less invasive brain-machine interfaces.

High Density Individually Addressable Nanowire Arrays Record Intracellular Activity from Primary Rodent and Human Stem Cell Derived Neurons.

We report a new hybrid integration scheme that offers for the first time a nanowire-on-lead approach, which enables independent electrical addressability, is scalable, and has superior spatial resolution in vertical nanowire arrays. The fabrication of these nanowire arrays is demonstrated to be scalable down to submicrometer site-to-site spacing and can be combined with standard integrated circuit fabrication technologies. We utilize these arrays to perform electrophysiological recordings from mouse and rat primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons, which revealed high signal-to-noise ratios and sensitivity to subthreshold postsynaptic potentials (PSPs). We measured electrical activity from rodent neurons from 8 days in vitro (DIV) to 14 DIV and from hiPSC-derived neurons at 6 weeks in vitro post culture with signal amplitudes up to 99 mV. Overall, our platform paves the way for longitudinal electrophysiological experiments on synaptic activity in human iPSC based disease models of neuronal networks, critical for understanding the mechanisms of neurological diseases and for developing drugs to treat them.

Diterpenoid phytoalexin factor, a bHLH transcription factor, plays a central role in the biosynthesis of diterpenoid phytoalexins in rice.

Rice (Oryza sativa) produces diterpenoid phytoalexins (DPs), momilactones and phytocassanes as major phytoalexins. Accumulation of DPs is induced in rice by blast fungus infection, copper chloride or UV light. Here, we describe a rice transcription factor named diterpenoid phytoalexin factor (DPF), which is a basic helix-loop-helix (bHLH) transcription factor. The gene encoding DPF is expressed mainly in roots and panicles, and is inducible in leaves by blast infection, copper chloride or UV. Expression of all DP biosynthetic genes and accumulation of momilactones and phytocassanes were remarkably increased and decreased in DPF over-expressing and DPF knockdown rice, respectively. These results clearly demonstrated that DPF positively regulates DP accumulation via transcriptional regulation of DP biosynthetic genes, and plays a central role in the biosynthesis of DPs in rice. Furthermore, DPF activated the promoters of COPALYL DIPHOSPHATE SYNTHASE2 (CPS2) and CYTOCHROME P450 MONOOXYGENASE 99A2 (CYP99A2), whose products are implicated in the biosynthesis of phytocassanes and momilactones, respectively. Mutations in the N-boxes in the CPS2 upstream region, to which several animal bHLH transcription factors bind, decreased CPS2 transcription, indicating that DPF positively regulates CPS2 transcription through the N-boxes. In addition, DPF partly regulates CYP99A2 through the N-box. This study demonstrates that DPF acts as a master transcription factor in DP biosynthesis.

Short grain1 decreases organ elongation and brassinosteroid response in rice.

We identified a short-grain mutant (Short grain1 (Sg1) Dominant) via phenotypic screening of 13,000 rice (Oryza sativa) activation-tagged lines. The causative gene, SG1, encodes a protein with unknown function that is preferentially expressed in roots and developing panicles. Overexpression of SG1 in rice produced a phenotype with short grains and dwarfing reminiscent of brassinosteroid (BR)-deficient mutants, with wide, dark-green, and erect leaves. However, the endogenous BR level in the SG1 overexpressor (SG1:OX) plants was comparable to the wild type. SG1:OX plants were insensitive to brassinolide in the lamina inclination assay. Therefore, SG1 appears to decrease responses to BRs. Despite shorter organs in the SG1:OX plants, their cell size was not decreased in the SG1:OX plants. Therefore, SG1 decreases organ elongation by decreasing cell proliferation. In contrast to the SG1:OX plants, RNA interference knockdown plants that down-regulated SG1 and a related gene, SG1-LIKE PROTEIN1, had longer grains and internodes in rachis branches than in the wild type. Taken together, these results suggest that SG1 decreases responses to BRs and elongation of organs such as seeds and the internodes of rachis branches through decreased cellular proliferation.

Elimination of contaminating amplified short tandem repeat products by autoclaving and ultraviolet irradiation.

DNA contamination can result in false interpretation of short tandem repeat (STR) DNA typing. Proper decontamination is particularly required in forensic DNA laboratories where probative value of the evidence may be affected. The aim of this study was to establish an effective DNA decontamination procedure for amplified STR products focusing on laboratory-related contamination. We verified the effectiveness of thermally and temporally extended autoclaving and ultraviolet irradiation for the elimination of contaminating amplified STR products. STR amplification products were prepared using a control genomic DNA template and generated using the AmpFℓSTR® Identifiler® Plus and Yfiler® polymerase chain reaction amplification kits. In this study, the contaminants were dried before decontamination treatment, which resembles actual contamination situations. One microlitre of amplified STR products was eliminated by a combination of autoclaving (128°C, 420 min) and UV irradiation (60 J/cm2). Our results reveal that the combination treatment represents an effective DNA decontamination procedure and a practicable method in standard level laboratories. Finally, we propose a comprehensive approach for forensic DNA laboratories to implement to minimise contamination issues and guarantee provision of authentic results.

Monolithic and Scalable Au Nanorod Substrates Improve PEDOT-Metal Adhesion and Stability in Neural Electrodes.

Poly(3,4-ethylenenedioxythiophene) or PEDOT is a promising candidate for next-generation neuronal electrode materials but its weak adhesion to underlying metallic conductors impedes its potential. An effective method of mechanically anchoring the PEDOT within an Au nanorod (Au-nr) structure is reported and it is demonstrated that it provides enhanced adhesion and overall PEDOT layer stability. Cyclic voltammetry (CV) stress is used to investigate adhesion and stability of spin-cast and electrodeposited PEDOT. The Au-nr adhesion layer permits 10 000 CV cycles of coated PEDOT film in phosphate buffered saline solution without delamination nor significant change of the electrochemical impedance, whereas PEDOT coating film on planar Au electrodes delaminates at or below 1000 cycles. Under CV stress, spin-cast PEDOT on planar Au delaminates, whereas electroplated PEDOT on planar Au encounters surface leaching/decomposition. After 5 weeks of accelerated aging tests at 60 °C, the electrodeposited PEDOT/Au-nr microelectrodes demonstrate a 92% channel survival compared to only 25% survival for spin-cast PEDOT on planar films. Furthermore, after a 10 week chronic implantation onto mouse barrel cortex, PEDOT/Au-nr microelectrodes do not exhibit delamination nor morphological changes, whereas the conventional PEDOT microelectrodes either partially or fully delaminate. Immunohistochemical evaluation demonstrates no or minimal response to the PEDOT implant.

Si Complies with GaN to Overcome Thermal Mismatches for the Heteroepitaxy of Thick GaN on Si.

Heteroepitaxial growth of lattice mismatched materials has advanced through the epitaxy of thin coherently strained layers, the strain sharing in virtual and nanoscale substrates, and the growth of thick films with intermediate strain-relaxed buffer layers. However, the thermal mismatch is not completely resolved in highly mismatched systems such as in GaN-on-Si. Here, geometrical effects and surface faceting to dilate thermal stresses at the surface of selectively grown epitaxial GaN layers on Si are exploited. The growth of thick (19 µm), crack-free, and pure GaN layers on Si with the lowest threading dislocation density of 1.1 × 107 cm-2 achieved to date in GaN-on-Si is demonstrated. With these advances, the first vertical GaN metal-insulator-semiconductor field-effect transistors on Si substrates with low leakage currents and high on/off ratios paving the way for a cost-effective high power device paradigm on an Si CMOS platform are demonstrated.

Autoclave Sterilization of PEDOT:PSS Electrophysiology Devices.

Autoclaving, the most widely available sterilization method, is applied to poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) electrophysiology devices. The process does not harm morphology or electrical properties, while it effectively kills E. coli intentionally cultured on the devices. This finding paves the way to widespread introduction of PEDOT:PSS electrophysiology devices to the clinic.

Strong Geometrical Effects in Submillimeter Selective Area Growth and Light Extraction of GaN Light Emitting Diodes on Sapphire.

Advanced semiconductor devices often utilize structural and geometrical effects to tailor their characteristics and improve their performance. We report here detailed understanding of such geometrical effects in the epitaxial selective area growth of GaN on sapphire substrates and utilize them to enhance light extraction from GaN light emitting diodes. Systematic size and spacing effects were performed side-by-side on a single 2" sapphire substrate to minimize experimental sampling errors for a set of 144 pattern arrays with circular mask opening windows in SiO2. We show that the mask opening diameter leads to as much as 4 times increase in the thickness of the grown layers for 20 µm spacings and that spacing effects can lead to as much as 3 times increase in thickness for a 350 µm dot diameter. We observed that the facet evolution in comparison with extracted Ga adatom diffusion lengths directly influences the vertical and lateral overgrowth rates and can be controlled with pattern geometry. Such control over the facet development led to 2.5 times stronger electroluminescence characteristics from well-faceted GaN/InGaN multiple quantum well LEDs compared to non-faceted structures.

BRASSINOSTEROID UPREGULATED1, encoding a helix-loop-helix protein, is a novel gene involved in brassinosteroid signaling and controls bending of the lamina joint in rice.

Brassinosteroids (BRs) are involved in many developmental processes and regulate many subsets of downstream genes throughout the plant kingdom. However, little is known about the BR signal transduction and response network in monocots. To identify novel BR-related genes in rice (Oryza sativa), we monitored the transcriptomic response of the brassinosteroid deficient1 (brd1) mutant, with a defective BR biosynthetic gene, to brassinolide treatment. Here, we describe a novel BR-induced rice gene BRASSINOSTEROID UPREGULATED1 (BU1), encoding a helix-loop-helix protein. Rice plants overexpressing BU1 (BU1:OX) showed enhanced bending of the lamina joint, increased grain size, and resistance to brassinazole, an inhibitor of BR biosynthesis. In contrast to BU1:OX, RNAi plants designed to repress both BU1 and its homologs displayed erect leaves. In addition, compared to the wild type, the induction of BU1 by exogenous brassinolide did not require de novo protein synthesis and it was weaker in a BR receptor mutant OsbriI (Oryza sativa brassinosteroid insensitive1, d61) and a rice G protein alpha subunit (RGA1) mutant d1. These results indicate that BU1 protein is a positive regulator of BR response: it controls bending of the lamina joint in rice and it is a novel primary response gene that participates in two BR signaling pathways through OsBRI1 and RGA1. Furthermore, expression analyses showed that BU1 is expressed in several organs including lamina joint, phloem, and epithelial cells in embryos. These results indicate that BU1 may participate in some other unknown processes modulated by BR in rice.