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Abstract Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells’ electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput. However, accessing intracellular potentials with NEAs remains challenging. This study presents an AI-supported technique that leverages thousands of synchronous eAP and iAP pairs from stem-cell-derived cardiomyocytes on NEAs. Our analysis revealed strong correlations between specific eAP and iAP features, such as amplitude and spiking velocity, indicating that extracellular signals could be reliable indicators of intracellular activity. We developed a physics-informed deep learning model to reconstruct iAP waveforms from extracellular recordings recorded from NEAs and Microelectrode arrays (MEAs), demonstrating its potential for non-invasive, long-term, high-throughput drug cardiotoxicity assessments. This AI-based model paves the way for future electrophysiology research across various cell types and drug interactions.more » « lessFree, publicly-accessible full text available December 1, 2026
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Abstract Sulfide solid-state electrolytes (SSEs) are promising candidates to realize all solid-state batteries (ASSBs) due to their superior ionic conductivity and excellent ductility. However, their hypersensitivity to moisture requires processing environments that are not compatible with today’s lithium-ion battery manufacturing infrastructure. Herein, we present a reversible surface modification strategy that enables the processability of sulfide SSEs (e. g., Li6PS5Cl) under humid ambient air. We demonstrate that a long chain alkyl thiol, 1-undecanethiol, is chemically compatible with the electrolyte with negligible impact on its ion conductivity. Importantly, the thiol modification extends the amount of time that the sulfide SSE can be exposed to air with 33% relative humidity (33% RH) with limited degradation of its structure while retaining a conductivity of above 1 mS cm-1for up to 2 days, a more than 100-fold improvement in protection time over competing approaches. Experimental and computational results reveal that the thiol group anchors to the SSE surface, while the hydrophobic hydrocarbon tail provides protection by repelling water. The modified Li6PS5Cl SSE maintains its function after exposure to ambient humidity when implemented in a Li0.5In | |LiNi0.8Co0.1Mn0.1O2ASSB. The proposed protection strategy based on surface molecular interactions represents a major step forward towards cost-competitive and energy-efficient sulfide SSE manufacturing for ASSB applications.more » « lessFree, publicly-accessible full text available December 1, 2026
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Abstract Due to its transparent and conductive nature, indium tin oxide (ITO) offers substantial benefits in several industries, such as thin film transistors, displays, and nanophotonics. Previous studies on ultrathin ITO have so far focused on its electrical properties but have neglected the technologically important epsilon-near-zero (ENZ) optical features due to the difficulty of extracting the refractive index and the thickness-dependent degradation of the optical properties. Here, we demonstrate a complementary metal-oxide-semiconductor (CMOS)-compatible deposition procedure for sub-percolation thickness (below 4 nm) ITO using a dry-etch assisted radiofrequency magnetron sputtering technique that yields continuous films in a precisely controlled manner. Through interface engineering and post-deposition annealing optimization, we show that these ITO films can retain high carrier mobility (43 cm2V−1s−1) while achieving a tunable near-zero-index (NZI) regime throughout the telecommunications band using a Berreman-assisted optical characterization technique. Our result opens the possibility of efficiently designing ENZ/NZI materials at the nanoscale using a robust fabrication approach for applications in nanophotonics.more » « lessFree, publicly-accessible full text available February 25, 2026
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Abstract The concept of employing highly concentrated electrolytes has been widely incorporated into electrolyte design, due to their enhanced Li‐metal passivation and oxidative stability compared to their diluted counterparts. However, issues such as high viscosity and sub‐optimal wettability, compromise their suitability for commercialization. In this study, we present a highly concentrated dimethyl ether‐based electrolyte that appears as a liquid phase at ambient conditions via Li+‐ solvents ion‐dipole interactions (Coulombic condensation). Unlike conventional high salt concentration ether‐based electrolytes, it demonstrates enhanced transport properties and fluidity. The anion‐rich solvation structure also contributes to the formation of a LiF‐rich salt‐derived solid electrolyte interphase, facilitating stable Li metal cycling for over 1000 cycles at 0.5 mA cm−2, 1 mAh cm−2condition. When combined with a sulfurized polyacrylonitrile (SPAN) electrode, the electrolyte effectively reduces the polysulfide shuttling effect and ensures stable performance across a range of charging currents, up to 6 mA cm−2. This research underscores a promising strategy for developing an anion‐rich, high concentration ether electrolyte with decreased viscosity, which supports a Li metal anode with exceptional temperature durability and rapid charging capabilities.more » « lessFree, publicly-accessible full text available February 17, 2026
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Abstract The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron’s action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.more » « less
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Abstract Triplet‐triplet annihilation upconversion (TTA‐UC) is a photophysical process in which two low‐energy photons are converted into one higher‐energy photon. This type of upconversion requires two species: a sensitizer that absorbs low‐energy light and transfers its energy to an annihilator, which emits higher‐energy light after TTA. In spite of the multitude of applications of TTA‐UC, few families of annihilators have been explored. In this work, we show dipyrrolonaphthyridinediones (DPNDs) can act as annihilators in TTA‐UC. We found that structural changes to DPND dramatically increase its upconversion quantum yield (UCQY). Our optimized DPND annihilator demonstrates a high maximum internal UCQY of 9.4 %, outperforming the UCQY of commonly used near‐infrared‐to‐visible annihilator rubrene by almost double.more » « less
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Abstract BackgroundBasic fibroblast growth factor (bFGF) is one of the critical components accelerating angiogenesis and tissue regeneration by promoting the migration of dermal fibroblasts and endothelial cells associated with matrix formation and remodeling in wound healing process. However, clinical applications of bFGF are substantially limited by its unstable nature due to rapid decomposition under physiological microenvironment. ResultsIn this study, we present the bFGF-loaded human serum albumin nanoparticles (HSA-bFGF NPs) as a means of enhanced stability and sustained release platform during tissue regeneration. Spherical shape of the HSA-bFGF NPs with uniform size distribution (polydispersity index < 0.2) is obtainedviaa simple desolvation and crosslinking process. The HSA-bFGF NPs securely load and release the intact soluble bFGF proteins, thereby significantly enhancing the proliferation and migration activity of human dermal fibroblasts. Myofibroblast-related genes and proteins were also significantly down-regulated, indicating decrease in risk of scar formation. Furthermore, wound healing is accelerated while achieving a highly organized extracellular matrix and enhanced angiogenesis in vivo. ConclusionConsequently, the HSA-bFGF NPs are suggested not only as a delivery vehicle but also as a protein stabilizer for effective wound healing and tissue regeneration.more » « less
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Abstract Multivalency is a fundamental principle in nature that leads to high‐affinity intermolecular recognition through multiple cooperative interactions that overcome the weak binding of individual constituents. For example, multivalency plays a critical role in lectin‐carbohydrate interactions that participate in many essential biological processes. Designing high‐affinity multivalent glycoconjugates that engage lectins results in systems with the potential to disrupt these biological processes, offering promising applications in therapeutic design and bioengineering. Here, a versatile and tunable synthetic platform for the synthesis of metallosupramolecular glycoassemblies is presented that leverages subcomponent self‐assembly, which employs metal ion templates to generate complex supramolecular architectures from simple precursors in one pot. Through ligand design, this approach provides precise control over molecular parameters such as size, shape, flexibility, valency, and charge, which afforded a diverse family of well‐defined hybrid glyconanoassemblies. Evaluation of these complexes as multivalent binders to Concanavalin A (Con A) by isothermal titration calorimetry (ITC) demonstrates the optimal saccharide tether length and the effect of electrostatics on protein affinity, revealing insights into the impact of synthetic design on molecular recognition. The presented studies offer an enhanced understanding of structure‐function relationships governing lectin‐saccharide interactions at the molecular level and guide a systematic approach towards optimizing glyconanoassembly binding parameters.more » « less
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Abstract Delivery of agrochemicals into soil presents a challenge, as the active ingredients are often hydrophobic and do not possess adequate soil mobility to reach their target pest. Previously, plant virus nanoparticles have been shown to penetrate soil and deliver agrochemicals for the treatment of plant parasitic nematodes. For example, tobacco mild green mosaic virus (TMGMV) can be functionalized with agrochemicals through bioconjugation, infusion at the coat protein interface, or encapsulation through thermal shapeshifting (rod-to-sphere). There continues to be a need to expand approaches for agrochemical display and delivery with a need for plug-and-play technology to be applicable for multiple nanoparticle platforms and agrochemicals. Toward this goal, we turned toward a bio-specific coupling strategy making use of the biotin-(strept)avidin system. Herein, we conjugated TMGMV with either avidin or biotin using azide-alkyne cycloaddition. The avidin/biotin-functionalized TMGMV nanoparticles were then characterized by gel electrophoresis and electron microscopy to confirm cargo loading and the nanoparticle’s structural integrity. Soil column assays confirmed that soil mobility was maintained upon chemical modification. Ivermectin modified with biotin or streptavidin linkers was then introduced to the TMGMV-avidin/biotin nanoparticles and binding propensity and loading were validated by QCM-D and a competitive ELISA. Finally, the ivermectin-loaded TMGMV nanoparticles were used to treatC. elegansin a gel burrowing assay, demonstrating that either pesticide loading strategy resulted in active TMGMV nanoparticle formulation that significantly reduced the mobility of nematodes, even after passing through soil. In stark contrast, free ivermectin only exhibited efficacy when applied directly to nematodes; the free pesticide was lost in the soil column—highlighting the need for a delivery system. The presented approach provides a facile plug-and-play approach for pesticide loading onto TMGMV nanoparticles. In particular, biotinylated TMGMV with streptavidin-conjugated ivermectin served as the most effective formulation. Importantly this method does not require heat, which contrasts our previous method of thermal reshaping that requires sample and pesticide exposure to temperatures > 96 °C. We envision the bio-specific loading strategy could be extended to other protein or inorganic nanoparticles to advance soil treatment strategies.more » « less
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Abstract Nonlinear microscopy provides excellent depth penetration and axial sectioning for 3D imaging, yet widespread adoption is limited by reliance on expensive ultrafast pulsed lasers. This work circumvents such limitations by employing rare‐earth doped upconverting nanoparticles (UCNPs), specifically Yb3+/Tm3+co‐doped NaYF4nanocrystals, which exhibit strong multimodal nonlinear optical responses under continuous‐wave (CW) excitation. These UCNPs emit multiple wavelengths at UV (λ ≈ 450 nm), blue (λ ≈ 450 nm), and NIR (λ ≈ 800 nm), whose intensities are nonlinearly governed by excitation power. Exploiting these properties, multi‐colored nonlinear emissions enable functional imaging of cerebral blood vessels in deep brain. Using a simple optical setup, high resolution in vivo 3D imaging of mouse cerebrovascular networks at depths up to 800 µmm is achieved, surpassing performance of conventional imaging methods using CW lasers. In vivo cerebrovascular flow dynamics is also visualized with wide‐field video‐rate imaging under low‐powered CW excitation. Furthermore, UCNPs enable depth‐selective, 3D‐localized photo‐modulation through turbid media, presenting spatiotemporally targeted light beacons. This innovative approach, leveraging UCNPs' intrinsic nonlinear optical characteristics, significantly advances multimodal nonlinear microscopy with CW lasers, opening new opportunities in bio‐imaging, remote optogenetics, and photodynamic therapy.more » « less
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