Soft, Multifunctional MXene-Coated Fiber Microelectrodes for Biointerfacing.

Flexible fiber-based microelectrodes allow safe and chronic investigation and modulation of electrically active cells and tissues. Compared to planar electrodes, they enhance targeting precision while minimizing side effects from the device-tissue mechanical mismatch. However, the current manufacturing methods face scalability, reproducibility, and handling challenges, hindering large-scale deployment. Furthermore, only a few designs can record electrical and biochemical signals necessary for understanding and interacting with complex biological systems. In this study, we present a method that utilizes the electrical conductivity and easy processability of MXenes, a diverse family of two-dimensional nanomaterials, to apply a thin layer of MXene coating continuously to commercial nylon filaments (30-300 µm in diameter) at a rapid speed (up to 15 mm/s), achieving a linear resistance below 10 Ω/cm. The MXene-coated filaments are then batch-processed into free-standing fiber microelectrodes with excellent flexibility, durability, and consistent performance even when knotted. We demonstrate the electrochemical properties of these fiber electrodes and their hydrogen peroxide (H2O2) sensing capability and showcase their applications in vivo (rodent) and ex vivo (bladder tissue). This scalable process fabricates high-performance microfiber electrodes that can be easily customized and deployed in diverse bioelectronic monitoring and stimulation studies, contributing to a deeper understanding of health and disease.

Bacteria intrinsic to Medicago sativa (alfalfa) reduce Salmonella enterica growth in planta.

AIMS: The purpose of this study was to determine whether plant-associated bacteria (PAB) can reduce Salmonella enterica colonization and infection of alfalfa sprouts to reduce the risk of foodborne illness. METHODS: We isolated PAB from alfalfa seeds and sprouts. Monoclonal isolates of the bacteria were obtained and tested for their ability to inhibit Salmonella Typhimurium growth in alfalfa sprouts over 6 days. Genome sequencing and annotation were used to construct draft genomes of the bacteria isolated in this study using Illumina sequencing platform. RESULTS: We observed that a cocktail of five PAB could reduce Salmonella growth in alfalfa sprouts from ∼108 to ∼105 CFU g-1, demonstrating a protective role. Genome sequencing revealed that these bacteria were members of the Pseudomonas, Pantoea, and Priestia genus, and did not possess genes that were pathogenic to plants or animals. CONCLUSIONS: This work demonstrates that PAB can be utilized to reduce pathogen levels in fresh produce, which may be synergistic with other technologies to improve the safety of sprouts and other fresh produce.

Latest advances on MXenes in biomedical research and health care.

The unique combination of physical and chemical properties of MXenes has propelled a growing number of applications in biomedicine and healthcare. The expanding library of MXenes with tunable properties is paving the way for high-performance, application-specific MXene-based sensing and therapeutic platforms. In this article, we highlight the emerging biomedical applications of MXenes with specific emphasis on bioelectronics, biosensors, tissue engineering, and therapeutics. We present examples of MXenes and their composites enabling novel technological platforms and therapeutic strategies, and elucidate potential avenues for further developments. Finally, we discuss the materials, manufacturing, and regulatory challenges that need to be synergistically addressed for the clinical translation of MXene-based biomedical technologies.

High Thermal Conductivity of Sandwich-Structured Flexible Thermal Interface Materials.

Thermal interfaces are vital for effective thermal management in modern electronics, especially in the emerging fields of flexible electronics and soft robotics that impose requirements for interface materials to be soft and flexible in addition to having high thermal performance. Here, a novel sandwich-structured thermal interface material (TIM) is developed that simultaneously possesses record-low thermal resistance and high flexibility. Frequency-domain thermoreflectance (FDTR) is employed to investigate the overall thermal performance of the sandwich structure. As the core of this sandwich, a vertically aligned copper nanowire (CuNW) array preserves its high intrinsic thermal conductivity, which is further enhanced by 60% via a thick 3D graphene (3DG) coating. The thin copper layers on the top and bottom play the critical roles in protecting the nanowires during device assembly. Through the bottom-up fabrication process, excellent contacts between the graphene-coated CuNWs and the top/bottom layer are realized, leading to minimal interfacial resistance. In total, the thermal resistance of the sandwich is determined as low as ~0.23 mm2  K W-1 . This work investigates a new generation of flexible thermal interface materials with an ultralow thermal resistance, which therefore renders the great promise for advanced thermal management in a wide variety of electronics.

Analyzing RNA-Protein Interactions by Cross-Link Rates and CLIP-seq Libraries.

UV cross-linking-based methods are the most common tool to explore in vivo RNA-protein interactions. UV cross-linking enables the freezing of direct interactions in the cell, which can then be mapped by high-throughput sequencing through a family of methods termed CLIP-seq. CLIP-seq measures the distribution of cross-link events by purifying a protein of interest and sequencing the covalently bound RNA fragments. However, there are disagreements and ambiguities as to which proteins are RNA-binding proteins and what interactions are significant as all proteins contact all RNAs at some frequency. Here we describe a protocol for both determining RNA-protein interactions through a combination of RNA library preparation and the measurement of absolute cross-link rates, which helps determine what proteins are RNA-binding proteins and what interactions are significant. This protocol, comprising an updated form of the easyCLIP protocol, describes guidelines for RNA library preparation, oligo and protein standard construction, and the measurement of cross-link rates. These methods are easily visualizable through their fluorescent labels and can be adapted to study RNA-binding properties of both functional, high affinity RNA-binding proteins, and the accidental RNA interactions of non-RNA-binding proteins. © 2023 Wiley Periodicals LLC. Basic Protocol 1: RNA library construction Basic Protocol 2: Determining UV cross-link rates Support Protocol 1: Cross-linking and lysing cells Support Protocol 2: Adapter preparation Support Protocol 3: Preparation of cross-linked RBP standard.

3D Graphene-Nanowire "Sandwich" Thermal Interface with Ultralow Resistance and Stiffness.

Despite the recent advancements of passive and active cooling solutions for electronics, interfaces between materials have generally become crucial barriers for thermal transport because of intrinsic material dissimilarity and surface roughness at interfaces. We demonstrate a 3D graphene-nanowire "sandwich" thermal interface that enables an ultralow thermal resistance of ∼0.24 mm2·K/W that is about 1 order of magnitude smaller than those of solders and several orders of magnitude lower than those of thermal greases, gels, and epoxies, as well as a low elastic and shear moduli of ∼1 MPa like polymers and foams. The flexible 3D "sandwich" exhibits excellent long-term reliability with >1000 cycles over a broad temperature range from -55 °C to 125 °C. This nanostructured thermal interface material can greatly benefit a variety of electronic systems and devices by allowing them to operate at lower temperatures or at the same temperature but with higher performance and higher power density.

Wearable High-Density MXene-Bioelectronics for Neuromuscular Diagnostics, Rehabilitation, and Assistive Technologies.

High-density surface electromyography (HDsEMG) allows noninvasive muscle monitoring and disease diagnosis. Clinical translation of current HDsEMG technologies is hampered by cost, limited scalability, low usability, and minimal spatial coverage. Here, this study presents, validates, and demonstrates the broad clinical applicability of dry wearable MXene HDsEMG arrays (MXtrodes) fabricated from safe and scalable liquid-phase processing of Ti3 C2 Tx . The fabrication scheme allows easy customization of array geometry to match subject anatomy, while the gel-free and minimal skin preparation enhance usability and comfort. The low impedance and high conductivity of the MXtrode arrays allow detection of the activity of large muscle groups at higher quality and spatial resolution than state-of-the-art wireless electromyography  sensors, and in realistic clinical scenarios. To demonstrate the clinical applicability of MXtrodes in the context of neuromuscular diagnostics and rehabilitation, simultaneous HDsEMG and biomechanical mapping of muscle groups across the whole calf during various tasks, ranging from controlled contractions to walking is shown. Finally, the integration of HDsEMG acquired with MXtrodes with a machine learning pipeline and the accurate prediction of the phases of human gait are shown. The results underscore the advantages and translatability of MXene-based wearable bioelectronics for studying neuromuscular function and disease, as well as for precision rehabilitation.

Neural modulation with photothermally active nanomaterials.

Modulating neural electrophysiology with high precision is essential for understanding neural communication and for the diagnosis and treatment of neural disorders. Photothermal modulation offers a remote and non-genetic method for neural modulation with high spatiotemporal resolution and specificity. This technique induces highly localized and transient temperature changes at the cell membrane interfaced with photothermally active nanomaterials. This rapid temperature change affects the electrical properties of the cell membrane or temperature-sensitive ion channels. In this Review, we discuss the fundamental material properties and illumination conditions that are necessary for nanomaterial-assisted photothermal neural excitation and inhibition. We examine how this versatile technique allows direct investigation of neural electrophysiology and signalling pathways in two-dimensional and three-dimensional cell cultures and tissues, and highlight the scientific and technological challenges in terms of cellular specificity, light delivery and biointerface stability on the road to clinical translation.

Intra-arterial injection of Diclofenac by informal health practitioner: A rare complication of a common drug.

Introduction and importance: Intra-arterial injections (IA) though rare, cause acute limb ischaemia with often catastrophic outcomes. Symptoms could progress rapidly and early identification and intervention could help in preventing the limb gangrene. Methodology: The work has been reported in line with the SCARE 2020 criteria:Agha RA, Franchi T, Sohrabi C, Mathew G, for the SCARE Group. The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines, International Journal of Surgery 2020; 84:226-230. Operative procedure was performed by consultant of general surgery. Case presentation: 38-year-old male presented to surgery casualty with history of sudden onset of pain and paraesthesia in the left forearm and palm followed by progressive weakness and discolouration, 15 hours following injection of Diclofenac in the mid cubital region. Clinical discussion: On examination, limb temperature was lower, finger movements were minimal. However, distal pulses were palpable, and duplex ultrasound showed normal triphasic flow. In view of the equivocal clinico-radiological findings, the patient underwent CT-Angiography of upper limb, which showed non-opacification of radial and ulnar arteries. Fasciotomy of forearm, brachial artery exploration and removal of embolus was attempted in a doubtful viable left upper limb. No thrombus was noted. Subsequently, he was managed conservatively, and cervical sympathectomy was done. As there was progressive deterioration in the viability of the limb, the patient underwent an above elbow amputation. Conclusion: Intra-arterial injections can lead to limb threatening gangrene, the course of which can be rapid A multidisciplinary team approach was necessary to arrive at a diagnosis and provide optimum care.

Modulation of Early Stage Neuronal Outgrowth through Out-of-Plane Graphene.

The correct wiring of a neural network requires neuron to integrate an incredible repertoire of cues found in their extracellular environment. The astonishing efficiency of this process plays a pivotal role in the correct wiring of the brain during development and axon regeneration. Biologically inspired micro- and nanostructured substrates have been shown to regulate axonal outgrowth. In parallel, several studies investigated graphene's potential as a conductive neural interface, able to enhance cell adhesion, neurite sprouting and outgrowth. Here, we engineered a 3D single- to few-layer fuzzy graphene morphology (3DFG), 3DFG on a collapsed Si nanowire (SiNW) mesh template (NT-3DFGc), and 3DFG on a noncollapsed SiNW mesh template (NT-3DFGnc) as neural-instructive materials. The micrometric protruding features of the NWs templates dictated neuronal growth cone establishment, as well as influencing axon elongation and branching. Furthermore, neurons-to-graphene coupling was investigated with comprehensive view of integrin-mediated contact adhesion points and plasma membrane curvature processes.

Flexible Glassy Carbon Multielectrode Array for In Vivo Multisite Detection of Tonic and Phasic Dopamine Concentrations.

Dopamine (DA) plays a central role in the modulation of various physiological brain functions, including learning, motivation, reward, and movement control. The DA dynamic occurs over multiple timescales, including fast phasic release, as a result of neuronal firing and slow tonic release, which regulates the phasic firing. Real-time measurements of tonic and phasic DA concentrations in the living brain can shed light on the mechanism of DA dynamics underlying behavioral and psychiatric disorders and on the action of pharmacological treatments targeting DA. Current state-of-the-art in vivo DA detection technologies are limited in either spatial or temporal resolution, channel count, longitudinal stability, and ability to measure both phasic and tonic dynamics. We present here an implantable glassy carbon (GC) multielectrode array on a SU-8 flexible substrate for integrated multichannel phasic and tonic measurements of DA concentrations. The GC MEA demonstrated in vivo multichannel fast-scan cyclic voltammetry (FSCV) detection of electrically stimulated phasic DA release simultaneously at different locations of the mouse dorsal striatum. Tonic DA measurement was enabled by coating GC electrodes with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) and using optimized square-wave voltammetry (SWV). Implanted PEDOT/CNT-coated MEAs achieved stable detection of tonic DA concentrations for up to 3 weeks in the mouse dorsal striatum. This is the first demonstration of implantable flexible MEA capable of multisite electrochemical sensing of both tonic and phasic DA dynamics in vivo with chronic stability.

Thermal Transport in Multidimensional Silicon-Graphene Hybrid Nanostructures.

In this work, we fabricate multidimensional silicon-graphene hybrid nanostructures composed of three-dimensional (3D) out-of-plane graphene flakes on a silicon nanowire core. By changing the synthesis temperature (700 and 1100 °C) and time (5, 10, and 20 min), we obtain two different types of 3D graphene flakes with tunable dimensions and structure parameters. We characterize the thermal transport behavior of this hybrid multidimensional material in a broad temperature range of 20-460 K. With different morphologies and structures, the effective thermal conductivity of the silicon-graphene hybrid nanostructures varies from 1 to 7 W/(m·K) at room temperature. We also apply molecular dynamics simulation and density functional theory to elucidate the thermal transport mechanisms in the silicon-graphene hybrid nanostructures.

Ti3C2Tx MXene Flakes for Optical Control of Neuronal Electrical Activity.

Understanding cellular electrical communications in both health and disease necessitates precise subcellular electrophysiological modulation. Nanomaterial-assisted photothermal stimulation was demonstrated to modulate cellular activity with high spatiotemporal resolution. Ideal candidates for such an application are expected to have high absorbance at the near-infrared window, high photothermal conversion efficiency, and straightforward scale-up of production to allow future translation. Here, we demonstrate two-dimensional Ti3C2Tx (MXene) as an outstanding candidate for remote, nongenetic, optical modulation of neuronal electrical activity with high spatiotemporal resolution. Ti3C2Tx's photothermal response measured at the single-flake level resulted in local temperature rises of 2.31 ± 0.03 and 3.30 ± 0.02 K for 635 and 808 nm laser pulses (1 ms, 10 mW), respectively. Dorsal root ganglion (DRG) neurons incubated with Ti3C2Tx film (25 µg/cm2) or Ti3C2Tx flake dispersion (100 µg/mL) for 6 days did not show a detectable influence on cellular viability, indicating that Ti3C2Tx is noncytotoxic. DRG neurons were photothermally stimulated using Ti3C2Tx films and flakes with as low as tens of microjoules per pulse incident energy (635 nm, 2 µJ for film, 18 µJ for flake) with subcellular targeting resolution. Ti3C2Tx's straightforward and large-scale synthesis allows translation of the reported photothermal stimulation approach in multiple scales, thus presenting a powerful tool for modulating electrophysiology from single-cell to additive manufacturing of engineered tissues.

3D fuzzy graphene microelectrode array for dopamine sensing at sub-cellular spatial resolution.

The development of a high sensitivity real-time sensor for multi-site detection of dopamine (DA) with high spatial and temporal resolution is of fundamental importance to study the complex spatial and temporal pattern of DA dynamics in the brain, thus improving the understanding and treatments of neurological and neuropsychiatric disorders. In response to this need, here we present high surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.12 ± 0.05 nA/nM, with LOD of 364.44 ± 8.65 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 × 2 µm2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.

Intracellular action potential recordings from cardiomyocytes by ultrafast pulsed laser irradiation of fuzzy graphene microelectrodes.

Graphene with its unique electrical properties is a promising candidate for carbon-based biosensors such as microelectrodes and field effect transistors. Recently, graphene biosensors were successfully used for extracellular recording of action potentials in electrogenic cells; however, intracellular recordings remain beyond their current capabilities because of the lack of an efficient cell poration method. Here, we present a microelectrode platform consisting of out-of-plane grown three-dimensional fuzzy graphene (3DFG) that enables recording of intracellular cardiac action potentials with high signal-to-noise ratio. We exploit the generation of hot carriers by ultrafast pulsed laser for porating the cell membrane and creating an intimate contact between the 3DFG electrodes and the intracellular domain. This approach enables us to detect the effects of drugs on the action potential shape of human-derived cardiomyocytes. The 3DFG electrodes combined with laser poration may be used for all-carbon intracellular microelectrode arrays to allow monitoring of the cellular electrophysiological state.

Bioelectrical interfaces with cortical spheroids in three-dimensions.

Objective.Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for the investigation of neurological disorders and drug discovery. The success of such a model system requires techniques that enable high-resolution functional readout across the entire spheroid. Conventional microelectrode arrays and implantable neural probes cannot monitor the electrophysiology (ephys) activity across the entire native 3D geometry of the cellular construct.Approach.Here, we demonstrate a 3D self-rolled biosensor array (3D-SR-BA) integrated with a 3D cortical spheroid culture for simultaneousin vitroephys recording, functional Ca2+imaging, while monitoring the effect of drugs. We have also developed a signal processing pipeline to detect neural firings with high spatiotemporal resolution from the ephys recordings based on established spike sorting methods.Main results.The 3D-SR-BAs cortical spheroid interface provides a stable, high sensitivity recording of neural action potentials (<50µV peak-to-peak amplitude). The 3D-SR-BA is demonstrated as a potential drug screening platform through the investigation of the neural response to the excitatory neurotransmitter glutamate. Upon addition of glutamate, the neural firing rates increased notably corresponding well with the functional Ca2+imaging.Significance.Our entire system, including the 3D-SR-BA integrated with neuronal spheroid culture, enables simultaneous ephys recording and functional Ca2+imaging with high spatiotemporal resolution in conjunction with chemical stimulation. We demonstrate a powerful toolset for future studies of tissue development, disease progression, and drug testing and screening, especially when combined with native spheroid cultures directly extracted from humans.

Toward sustainable desalination using food waste: capacitive desalination with bread-derived electrodes.

Each year approximately 1.3 billion tons of food is either wasted or lost. One of the most wasted foods in the world is bread. The ability to reuse wasted food in another area of need, such as water scarcity, would provide a tremendous sustainable outcome. To address water scarcity, many areas of the world are now implementing desalination. One desalination technology that could benefit from food waste reuse is capacitive deionization (CDI). CDI has emerged as a powerful desalination technology that essentially only requires a pair of electrodes and a low-voltage power supply. Developing freestanding carbon electrodes from food waste could lower the overall cost of CDI systems and the environmental and economic impact from food waste. We created freestanding CDI electrodes from bread. The electrodes possessed a hierarchical pore structure that enabled both high salt adsorption capacity and one of the highest reported values for hydraulic permeability to date in a flow-through CDI system. We also developed a sustainable technique for electrode fabrication that does not require the use of common laboratory equipment and could be deployed in decentralized locations and developing countries with low-financial resources.

Graphene nanostructures for input-output bioelectronics.

The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased tissue states. This has primarily been achieved via input/output (I/O) bioelectronics that interface engineered materials with biological entities. Stable long-term application of conventional I/O bioelectronics advances as materials and processing techniques develop. Recent advancements have facilitated the development of graphene-based I/O bioelectronics with a wide variety of functional characteristics. Engineering the structural, physical, and chemical properties of graphene nanostructures and integration with modern microelectronics have enabled breakthrough high-density electrophysiological investigations. Here, we review recent advancements in 2D and 3D graphene-based I/O bioelectronics and highlight electrophysiological studies facilitated by these emerging platforms. Challenges and present potential breakthroughs that can be addressed via graphene bioelectronics are discussed. We emphasize the need for a multidisciplinary approach across materials science, micro-fabrication, and bioengineering to develop the next generation of I/O bioelectronics.

Remote nongenetic optical modulation of neuronal activity using fuzzy graphene.

The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.

Electron Transport in Multidimensional Fuzzy Graphene Nanostructures.

Atomically thin two-dimensional (2D) materials offer a range of superlative electronic and electrochemical properties that facilitate applications in sensing, energy conversion, and storage. Graphene, a 2D allotrope of carbon, has exceptional surface area per unit mass and highly catalytic edges. To leverage these properties, efforts have been made to synthesize complex three-dimensional (3D) geometries of graphene, with an eye toward integration into functional electronic devices. However, the electronic transport properties of such complex 3D structures are not well understood at a microscopic level. Here, we report electron transport in a 3D arrangement of free-standing 2D graphene flakes along an isolated one-dimensional Si nanowire. We show that transport through the free-standing graphene network is dominated by variable-range hopping and leads to negative magnetoresistance, from cryogenic conditions up to room temperature. Our findings lay the foundation for studying transport mechanisms in 2D material-based multidimensional nanostructures.