Gold nanostructures: synthesis, properties, and neurological applications.

Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both in vitro and in vivo experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.

Diurnal in vivo xylem sap glucose and sucrose monitoring using implantable organic electrochemical transistor sensors.

Bioelectronic devices that convert biochemical signals to electronic readout enable biosensing with high spatiotemporal resolution. These technologies have been primarily applied in biomedicine while in plants sensing is mainly based on invasive methods that require tissue sampling, hindering in-vivo detection and having poor spatiotemporal resolution. Here, we developed enzymatic biosensors based on organic electrochemical transistors (OECTs) for in-vivo and real-time monitoring of sugar fluctuations in the vascular tissue of trees. The glucose and sucrose OECT-biosensors were implanted into the vascular tissue of trees and were operated through a low-cost portable unit for 48hr. Our work consists a proof-of-concept study where implantable OECT-biosensors not only allow real-time monitoring of metabolites in plants but also reveal new insights into diurnal sugar homeostasis. We anticipate that this work will contribute to establishing bioelectronic technologies as powerful minimally invasive tools in plant science, agriculture and forestry.

Thermo-plasmonic gold nanofilms for simple and mass-producible photothermal neural interfaces.

In recent years, photothermal stimulation methods using plasmonic metal nanoparticles have emerged as non-genetic optical techniques in neuromodulation. Although nanoparticle-based photothermal stimulation shows great potential in the excitation and the inhibition of neural activity, the complex synthesis processes of the nanoparticles and the lack of large-area deposition methods can be limiting factors for the development of photothermal neural devices. In this paper, we propose a plasmonic gold nanofilm, fabricated by a standard thermal evaporation process, as a simple and mass-producible photothermal neural interface layer for microelectrode array (MEA) chips. The absorption of the gold nanofilm at near infrared wavelengths is optimized to maximize the photothermal effect by varying the thickness and microstructure of the gold nanofilm. With the optimized conditions, a significantly strong photothermal effect is applied on MEAs without affecting the neural signal recording capability. Finally, primary rat hippocampal neuronal cultures are used to show that the photothermal neural inhibition using the gold nanofilm is as effective as that using the plasmonic nanoparticles. Due to the greater simplicity and versatility of the fabrication process, the plasmonic gold nanofilm can provide a promising solution for the mass production of photothermal platforms.

Inkjet-Printed Biofunctional Thermo-Plasmonic Interfaces for Patterned Neuromodulation.

Localized heat generation by the thermo-plasmonic effect of metal nanoparticles has great potential in biomedical engineering research. Precise patterning of the nanoparticles using inkjet printing can enable the application of the thermo-plasmonic effect in a well-controlled way (shape and intensity). However, a universally applicable inkjet printing process that allows good control in patterning and assembly of nanoparticles with good biocompatibility is missing. Here we developed inkjet-printing-based biofunctional thermo-plasmonic interfaces that can modulate biological activities. We found that inkjet printing of plasmonic nanoparticles on a polyelectrolyte layer-by-layer substrate coating enables high-quality, biocompatible thermo-plasmonic interfaces across various substrates (rigid/flexible, hydrophobic/hydrophilic) by induced contact line pinning and electrostatically assisted nanoparticle assembly. We experimentally confirmed that the generated heat from the inkjet-printed thermo-plasmonic patterns can be applied in micrometer resolution over a large area. Lastly, we demonstrated that the patterned thermo-plasmonic effect from the inkjet-printed gold nanorods can selectively modulate neuronal network activities. This inkjet printing process therefore can be a universal method for biofunctional thermo-plasmonic interfaces in various bioengineering applications.

Inkjet-Printed Multiwavelength Thermoplasmonic Images for Anticounterfeiting Applications.

Inkjet printing of thermoplasmonic nanoparticles enables instantaneous, large-area heat pattern generation upon light illumination from distance. By printing multiple metal nanoparticles of different shapes overlaid, we can fabricate multiwavelength thermoplasmonic images, which generate different heat patterns from a single printed image depending on the wavelength choice of light. In this work, we propose a novel multiwavelength thermoplasmonic image printing process that can be used for anticounterfeit technology. With this technology, "printed thermoplasmonic labels" allow fully secured anticounterfeit inspection procedure. Input stimulus of near-infrared or infrared light illumination and output signal reading of thermal patterns can be both completely invisible. Wavelength selective photothermal effect also enables the encryption of the contained information, which adds more complexity and thus higher security.

Gold nanostar-mediated neural activity control using plasmonic photothermal effects.

Nanomaterials have emerged as an essential tool for the understanding of cellular level mechanism in the fields of biology and medical science. Recently, researchers have been studying the regulation of neuronal activity using plasmonic nanoparticles and light, and it has been reported that photothermal effects could lead to both excitation and inhibition of neuronal cells. So far, only a few photothermal transducers have been applied to modulate neural activity. In this paper, we synthesized biocompatible gold nanostars (AuNSs) which generate heat by absorbing near-infrared (NIR) light. And we used the AuNS to inhibit the activity of neurons through light stimulation. We have demonstrated that AuNS inhibits the neural activity by NIR laser in both chip-attached mode and cell-attached mode. We also confirmed the suppression of single neuron signal by using digital micromirror device (DMD) set up. This approach is possible to inhibit the neural firing by controlling the intensity of light, and overcome the disadvantages of conventional electrochemical stimulation methods. This method of NIR-mediated stimulating neurons using light sensitive AuNS will be a powerful tool for neuromodulation researches and neuroscience studies.

Emerging neural stimulation technologies for bladder dysfunctions.

In the neural engineering field, physiological dysfunctions are approached by identifying the target nerves and providing artificial stimulation to restore the function. Neural stimulation and recording technologies play a central role in this approach, and various engineering devices and stimulation techniques have become available to the medical community. For bladder control problems, electrical stimulation has been used as one of the treatments, while only a few emerging neurotechnologies have been used to tackle these problems. In this review, we introduce some recent developments in neural stimulation technologies including microelectrode array, closed-loop neural stimulation, optical stimulation, and ultrasound stimulation.

Angle-resolved light scattering of individual rod-shaped bacteria based on Fourier transform light scattering.

Two-dimensional angle-resolved light scattering maps of individual rod-shaped bacteria are measured at the single-cell level. Using quantitative phase imaging and Fourier transform light scattering techniques, the light scattering patterns of individual bacteria in four rod-shaped species (Bacillus subtilis, Lactobacillus casei, Synechococcus elongatus, and Escherichia coli) are measured with unprecedented sensitivity in a broad angular range from -70° to 70°. The measured light scattering patterns are analyzed along the two principal axes of rod-shaped bacteria in order to systematically investigate the species-specific characteristics of anisotropic light scattering. In addition, the cellular dry mass of individual bacteria is calculated and used to demonstrate that the cell-to-cell variations in light scattering within bacterial species is related to the cellular dry mass and growth.

Temporal and spatial downregulation of Arabidopsis MET1 activity results in global DNA hypomethylation and developmental defects.

DNA methylation is an epigenetic mechanism for gene silencing. In Arabidopsis, MET1 is the primary DNA methyltransferase that maintains CG DNA methylation. Plants having an overall reduction of MET1 activity, caused by a met1 mutation or a constitutively expressed MET1 antisense gene, display genome hypomethylation, inappropriate gene and transposon transcription, and developmental abnormalities. However, the effect of atransient reduction in MET1 activity caused by inhibiting MET1 expression in a restricted set of cells is not known. For this reason, we generated transgenic plants with a MET1 antisense gene fused to the DEMETER (DME) promoter (DME:MET1 a/s). Here we show that DME is expressed in leaf primordia, lateral root primoridia, in the region distal to the primary root apical meristem, which are regions that include proliferating cells. Endogenous MET1 expression was normal in organs where the DME:MET1 a/s was not expressed. Although DME promoter is active only in a small set of cells, these plants displayed global developmental abnormalities. Moreover, centromeric repeats were hypomethylated. The developmental defects were accumulated by the generations. Thus, not maintaining CG methylation in a small population of proliferating cells flanking the meristems causes global developmental and epigenetic abnormalities that cannot be rescued by restoring MET1 activity. These results suggest that during plant development there is little or no short-term molecular memory for reestablishing certain patterns of CG methylation that are maintained by MET1. Thus, continuous MET1 activity in dividing cells is essential for proper patterns of CG DNA methylation and development.