Proof of Concept for Sustainable Manufacturing of Neural Electrode Array for In Vivo Recording.

Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well.

An Environmental-Inert and Highly Self-Healable Elastomer Obtained via Double-Terminal Aromatic Disulfide Design and Zwitterionic Crosslinked Network for Use as a Triboelectric Nanogenerator.

Due to the ongoing development of portable/mobile electronics, sources to power have received widespread attention. Compared to chemical batteries as power sources, triboelectric nanogenerators (TENGs) possess lots of advantages, including the ability to harvest energy via human motions, flexible structures, environment-friendliness, and long-life characteristics. Although many self-healable TENGs are reported, the achievement of a muscle-like elasticity and the ability to recover from inevitable damage under extreme conditions (such as a high/low temperature and/or humidity) remain a challenge. Herein, a "double-terminal aromatic disulfide" on a structure with zwitterions as branched chains is reported to engineer the high-efficient self-healable elastomer for application in a flexible TENG. The as-designed material exhibits a repeatable elastic recovery (at 250% elongation) and a self-healing efficiency with an ultimate tensile stress of 96% over 2 h, representing an improvement on previously reported disulfide-based elastomers. The elastomer can autonomously recover by 50% even at a subzero temperature of -30 °C within 24 h. The elastomer-based TENG, as a self-driven sensor for detecting human behavior, is demonstrated to exhibit stable outputs and self-healing in the temperature range of -30 to 60 °C, and so is expected to promote the development of self-powered electronics for next-generation human-machine communications.

Flexible Optogenetic Transducer Device for Remote Neuron Modulation Using Highly Upconversion-Efficient Dendrite-Like Gold Inverse Opaline Structure.

A remote optogenetic device for analyzing freely moving animals has attracted extensive attention in optogenetic engineering. In particular, for peripheral nerve regions, a flexible device is needed to endure the continuous bending movements of these areas. Here, a remote optogenetic optical transducer device made from a gold inverse opaline skeleton grown with a dendrite-like gold nanostructure (D-GIOF) and chemically grafted with upconversion nanoparticles (UCNPs) is developed. This implantable D-GIOF-based transducer device can achieve synergistic interaction of the photonic crystal effect and localized surface plasmon resonance, resulting in considerable UCNP conversion efficiency with a negligible thermal effect under low-intensity 980 nm near-infrared (NIR) light excitation. Furthermore, the D-GIOF-based transducer device exhibits remarkable emission power retention (≈100%) under different bending states, indicating its potential for realizing peripheral nerve stimulation. Finally, the D-GIOF-based transducer device successfully stimulates neuronal activities of the sciatic nerve in mice. This study demonstrates the potential of the implantable device to promote remote NIR stimulation for modulation of neural activity in peripheral nerve regions and provides proof of concept for its in vivo application in optogenetic engineering.

Waffle-Like Carbons Combined with Enriched Mesopores and Highly Heteroatom-Doped Derived from Sandwiched MOF/LDH/MOF for High-Rate Supercapacitor.

Supercapacitors (SCs) are promising for powering mobile devices, electric vehicles and smart power grids due to their fast charge/discharge rate, high power capability and robust cycle stability. Nitrogen-doped porous carbons are great alternatives because they provide pseudocapacitance without losing their power rate. Nanoporous carbon derived from metal organic frameworks (MOFs) is an ideal precursor for preparing heteroatom-doped carbons due to their abundant nitrogen contents and incredible specific surface areas. However, severe aggregations and the leakage of nitrogen can occur during harsh carbonization. In this study, we used CoAl-LDH (cobalt aluminum layered double hydroxide) as an in-situ growth substrate, allowing Co-based MOF to uniformly grow onto the CoAl-LDH to form a sandwiched MOF/LDH/MOF structure. After acid etching, we obtained waffle-like nanoporous carbons (WNPC). WNPC exhibited high nitrogen and oxygen retention (7.5 wt% and 9.1 wt%) and a broad mesopores distribution with specific surface areas of 594 m2g-1, which promoted a sieving effect. This renders a specific capacitance of 300.7 F·g-1 at 1 A·g-1 and the high retention (72%) of capacitance at 20 A·g-1, ensuring its use at high-rate supercapacitor electrodes. Finally, the WNPC symmetric supercapacitor reaches a superior specific energy of 27 W·h·kg-1 at a power of 500 W·kg-1, and a good cycle stability (85% capacitance retention after 10,000 cycles).

Gene-Embedded Nanostructural Biotic-Abiotic Optoelectrode Arrays Applied for Synchronous Brain Optogenetics and Neural Signal Recording.

Optogenetics is a recently established neuromodulation technique in which photostimulation is used to manipulate neurons with high temporal and spatial precision. However, sequential genetic and optical insertion with double brain implantation tends to cause excessive tissue damage. In addition, the incorporation of light-sensitive genes requires the utilization of viral vectors, which remains a safety concern. Here, by combining device fabrication design, nanotechnology, and cell targeting technology, we developed a new gene-embedded optoelectrode array for neural implantation to enable spatiotemporal electroporation (EP) for gene delivery/transfection, photomodulation, and synchronous electrical monitoring of neural signals in the brain via one-time implantation. A biotic-abiotic neural interface (called PG) composed of reduced graphene oxide and conductive polyelectrolyte 3,4-ethylenedioxythiophene-modified amphiphilic chitosan was developed to form a nanostructural hydrogel with assembled nanodomains for encapsulating nonviral gene vectors (called PEI-NT-pDNA) formulated by neurotensin (NT) and polyethylenimine (PEI)-coupled plasmid DNA (pDNA). The PG can maintain high charge storage ability to respond to a minimal current of 125 µA for controllable gene delivery. The in vitro analysis of PG-PEI-NT-pDNA on the microelectrode array chip showed that the microelectrodes provided electrically inductive electropermeabilization, which permitted gene transfection into localized rat adrenal pheochromocytoma cells with a strong green fluorescent protein expression that was up to 8-fold higher than that in nontreated cells. Furthermore, the in vivo implantation enabled on-demand spatiotemporal gene transfection to neurons with 10-fold enhancement of targeting ability compared with astrocytes. Finally, using the real optogenetic opsin channelrhodopsin-2, the flexible neural probe incorporated with an optical waveguide fiber displayed photoevoked extracellular spikes in the thalamic ventrobasal region after focal EP for only 7 days, which provided a proof of concept for the use of photomodulation to facilitate neural therapies.

Highly sensitive/selective 3D nanostructured immunoparticle-based interface on a multichannel sensor array for detecting amyloid-beta in Alzheimer's disease.

Accumulation of ß-amyloid (Aß) peptides is highly associated with Alzheimer's disease (AD) progression in prevailing studies. The successful development of an ultrasensitive detection assay for Aß is a challenging task, especially from blood-based samples. Methods: We have developed a one-step electrophoresis/electropolymerization strategy for preparing a CSIP hierarchical immunoelectrochemical interface that is easily integrated into a PoCT device. The interface includes conductive silk fibroin-based immunoparticles (CSIPs) via electropolymerized Poly(3,4-ethylenedioxythiophene) (PEDOT) bridging to enable on-site electrochemical detection of serum amyloid-ß42 (Aß42) and -ß40 (Aß40) peptides from an AD blood test. In addition, micro-positron emission tomography (microPET) neuroimaging and behavioral tests were simultaneously performed. Results: This nanostructured conductive interface favors penetration of water-soluble biomolecules and catalyzes a redox reaction, providing limits of detection (LOD) of 6.63 pg/mL for Aß40 and 3.74 pg/mL for Aß42. Our proof-of-concept study confirms that the multi-sensing electrochemical immunosensor array (MEIA) platform enables simultaneous measurement of serum Aß42 and Aß40 peptide levels and is more informative in early stage AD animals than amyloid-labeling Aß plaque PET imaging and behavioral tests. Conclusion: We believe this study greatly expands the applications of silk fibroin-based materials, is an important contribution to the advancement of biomaterials, and would also be valuable in the design of new types of multichannel electrochemical immunosensor arrays for the detection of other diseases.

Implantable Graphene-based Neural Electrode Interfaces for Electrophysiology and Neurochemistry in In Vivo Hyperacute Stroke Model.

Implantable microelectrode arrays have attracted considerable interest due to their high temporal and spatial resolution recording of neuronal activity in tissues. We herein presented an implantable multichannel neural probe with multiple real-time monitoring of neural-chemical and neural-electrical signals by a nonenzymatic neural-chemical interface, which was designed by creating the newly developed reduced graphene oxide-gold oxide (rGO/Au2O3) nanocomposite electrode. The modified electrode on the neural probe was prepared by a facile one-step cyclic voltammetry (CV) electrochemical method with simultaneous occurrence of gold oxidation and GOs reduction to induce the intimate attachment by electrostatic interaction using chloride ions (Cl(-)). The rGO/Au2O3-modified electrode at a low deposition scan rate of 10 mVs(-1) displayed significantly improved electrocatalytic activity due to large active areas and well-dispersive attached rGO sheets. The in vitro amperometric response to H2O2 demonstrated a fast response of less than 5 s and a very low detection limit of 0.63 µM. In in vivo hyperacute stroke model, the concentration of H2O2 was measured as 100.48 ± 4.52 µM for rGO/Au2O3 electrode within 1 h photothrombotic stroke, which was much higher than that (71.92 µM ± 2.52 µM) for noncoated electrode via in vitro calibration. Simultaneously, the somatosensory-evoked potentials (SSEPs) test provided reliable and precise validation for detecting functional changes of neuronal activities. This newly developed implantable probe with localized rGO/Au2O3 nanocomposite electrode can serve as a rapid and reliable sensing platform for practical H2O2 detection in the brain or for other neural-chemical molecules in vivo.

Synergistic hierarchical silicone-modified polysaccharide hybrid as a soft scaffold to control cell adhesion and proliferation.

In this study, a new type of polydimethylsiloxane-modified chitosan (PMSC) amphiphilic hydrogel was developed as a soft substrate to explore cellular responses for dermal reconstruction. The hydrogel wettability, mechanical stiffness and topography were controllable through manipulation of the degree of esterification (DE) between hydrophobic polydimethylsiloxane (PDMS) and hydrophilic N,O-(carboxymethyl)-chitosan (NOCC). Based on microphase separation, the incorporation of PDMS into NOCC increased the stiffness of the hybrid through the formation of self-assembled aggregates, which also provided anchor sites for cell adhesion. As the DE exceeded 0.39, the size of the PDMS-rich aggregates changed from nanoscale to microscale. Subsequently, the hierarchical architecture resulted in an increase in the tensile modulus of the hybrid gel up to fourfold, which simultaneously provided mechano-topographic guidance and allowed the cells to completely spread to form spindle shapes instead of forming a spherical morphology, as on NOCC (DE=0). The results revealed that the incorporation of hydrophobic PDMS not only impeded acidic damage resulting from NOCC but also acted as an adhesion modification agent to facilitate long-term cell adhesion and proliferation on the soft substrate. As proved by the promotion on long-term type-I collagen production, the PMSC hybrid with self-assembled mechano-topography offers great promise as an advanced scaffold material for use in healing applications.

Remotely nano-rupturable yolk/shell capsules for magnetically-triggered drug release.

Yolk/shell capsules containing a volume/hydrophobicity transformable core and an ultra-thin silica shell have been prepared. When an external magnetic field induced the temperature, the cores exhibit a significant triggering size shrinkage and the diameter decreases more than 10 times, causing solid shells destruction and physical collapse, leading to drug burst release.