Adaptive Gap-Tunable Surface-Enhanced Raman Spectroscopy.

Gap plasmon (GP) resonance in static surface-enhanced Raman spectroscopy (SERS) structures is generally too narrow and not tunable. Here, we present an adaptive gap-tunable SERS device to selectively enhance and modulate different vibrational modes via active flexible Au nanogaps, with adaptive optical control. The tunability of GP resonance is up to ∼1200 cm-1 by engineering gap width, facilitated by mechanical bending of a polyethylene terephthalate substrate. We confirm that the tuned GP resonance selectively enhances different Raman spectral regions of the molecules. Additionally, we dynamically control the SERS intensity through the wavefront shaping of excitation beams. Furthermore, we demonstrate simulation results, exhibiting the mechanical and optical properties of a one-dimensional flexible nanogap and their advantage in high-speed biomedical sensing. Our work provides a unique approach for observing and controlling the enhanced chemical responses with dynamic tunability.

Nanoscale Manipulation of Exciton-Trion Interconversion in a MoSe2 Monolayer via Tip-Enhanced Cavity-Spectroscopy.

Emerging light-matter interactions in metal-semiconductor hybrid platforms have attracted considerable attention due to their potential applications in optoelectronic devices. Here, we demonstrate plasmon-induced near-field manipulation of trionic responses in a MoSe2 monolayer using tip-enhanced cavity-spectroscopy (TECS). The surface plasmon-polariton mode on the Au nanowire can locally manipulate the exciton (X0) and trion (X-) populations of MoSe2. Furthermore, we reveal that surface charges significantly influence the emission and interconversion processes of X0 and X-. In the TECS configuration, the localized plasmon significantly affects the distributions of X0 and X- due to the modified radiative decay rate. Additionally, within the TECS cavity, the electric doping effect and hot electron generation enable dynamic interconversion between X0 and X- at the nanoscale. This work advances our understanding of plasmon-exciton-hot electron interactions in metal-semiconductor-metal hybrid structures, providing a foundation for an optimal trion-based nano-optoelectronic platform.

Pseudomorphic Synthesis of Monodisperse Afterglow Carbon Dot-Doped SiO2 Microparticles for Photonic Crystals.

Synthesizing monodisperse afterglow microparticles (MPs) is crucial for creating photonic crystal (PC) platforms with multiple optical states for optoelectronics. However, achieving high uniformity in both size and morphology is challenging for inorganic afterglow MPs using conventional methods. In this contribution, a novel approach for the synthesis of carbon dot (CD)-doped SiO2 MPs with tunable afterglow properties and size distributions is reported. These mechanism studies suggest that the pseudomorphic transformation of SiO2 MPs enables CD doping, providing a hydrogen bond-enriched environment for triplet state stabilization, which generates green afterglow while retaining the uniformity in size and morphology of the parent SiO2 MPs. Furthermore, the utility of CD-doped SiO2 MPs in the fabrication of rationally designed PC patterns is shown using a combined consecutive dip-coating and laser-assisted etching strategy. The pattern displays multiple optical responses under different lighting conditions, including angle-dependent structural colors and blue luminescence under daylight and upon 365-nm irradiation, respectively, as well as time-dependent green afterglow after ceasing UV excitation. The findings pave the way for further controlling the dynamics of spontaneous emissions by PCs to enable complicated optical states for advanced photonics.

Efficient X-ray luminescence imaging with ultrastable and eco-friendly copper(I)-iodide cluster microcubes.

The advancement of contemporary X-ray imaging heavily depends on discovering scintillators that possess high sensitivity, robust stability, low toxicity, and a uniform size distribution. Despite significant progress in this field, the discovery of a material that satisfies all of these criteria remains a challenge. In this study, we report the synthesis of monodisperse copper(I)-iodide cluster microcubes as a new class of X-ray scintillators. The as-prepared microcubes exhibit remarkable sensitivity to X-rays and exceptional stability under moisture and X-ray exposure. The uniform size distribution and high scintillation performance of the copper(I)-iodide cluster microcubes make them suitable for the fabrication of large-area, flexible scintillating films for X-ray imaging applications in both static and dynamic settings.

Indefinite and bidirectional near-infrared nanocrystal photoswitching.

Materials whose luminescence can be switched by optical stimulation drive technologies ranging from superresolution imaging1-4, nanophotonics5, and optical data storage6,7, to targeted pharmacology, optogenetics, and chemical reactivity8. These photoswitchable probes, including organic fluorophores and proteins, can be prone to photodegradation and often operate in the ultraviolet or visible spectral regions. Colloidal inorganic nanoparticles6,9 can offer improved stability, but the ability to switch emission bidirectionally, particularly with near-infrared (NIR) light, has not, to our knowledge, been reported in such systems. Here, we present two-way, NIR photoswitching of avalanching nanoparticles (ANPs), showing full optical control of upconverted emission using phototriggers in the NIR-I and NIR-II spectral regions useful for subsurface imaging. Employing single-step photodarkening10-13 and photobrightening12,14-16, we demonstrate indefinite photoswitching of individual nanoparticles (more than 1,000 cycles over 7 h) in ambient or aqueous conditions without measurable photodegradation. Critical steps of the photoswitching mechanism are elucidated by modelling and by measuring the photon avalanche properties of single ANPs in both bright and dark states. Unlimited, reversible photoswitching of ANPs enables indefinitely rewritable two-dimensional and three-dimensional multilevel optical patterning of ANPs, as well as optical nanoscopy with sub-Å localization superresolution that allows us to distinguish individual ANPs within tightly packed clusters.

Color-Tunable and Stable Copper Iodide Cluster Scintillators for Efficient X-Ray Imaging.

The search for color-tunable, efficient, and robust scintillators plays a vital role in the development of modern X-ray radiography. The radioluminescence tuning of copper iodide cluster scintillators in the entire visible region by bandgap engineering is herein reported. The bandgap engineering benefits from the fact that the conduction band minimum and valence band maximum of copper iodide cluster crystals are contributed by atomic orbitals from the inorganic core and organic ligand components, respectively. In addition to high scintillation performance, the as-prepared crystalline copper iodide cluster solids exhibit remarkable resistance toward both moisture and X-ray irradiation. These features allow copper iodide cluster scintillators to show particular attractiveness for low-dose X-ray radiography with a detection limit of 55 nGy s-1 , a value ≈100 times lower than a standard dosage for X-ray examinations. The results suggest that optimizing both inorganic core and organic ligand for the building blocks of metal halide cluster crystals may provide new opportunities for a new generation of high-performance scintillation materials.

Correction: Visualization of intercellular cargo transfer using upconverting nanoparticles.

Correction for 'Visualization of intercellular cargo transfer using upconverting nanoparticles' by Yeongchang Goh et al., Nanoscale, 2022, https://doi.org/10.1039/d2nr01999j.

Visualization of intercellular cargo transfer using upconverting nanoparticles.

Cell-cell communication is important for cellular differentiation, organ function, and immune responses. In intercellular communication, the extracellular vesicles (EVs) play a significant role in delivering the cargo molecules such as genes, proteins, and enzymes, to regulate and control the ability of the recipient cells. In this study, the observation of intercellular cargo transfer via dual-colour imaging using upconverting nanoparticles (UCNPs) has been demonstrated. Using this technique, the intercellular transport via contact-dependent and contact-independent signaling in live HeLa cells was clearly visualized with real-time, long-term single-vesicle tracking. Furthermore, it was demonstrated that the endocytosed UCNPs can be transmitted with the encapsulation of EVs labelled with fluorescent proteins.

Conformational heterogeneity of molecules physisorbed on a gold surface at room temperature.

A quantitative single-molecule tip-enhanced Raman spectroscopy (TERS) study at room temperature remained a challenge due to the rapid structural dynamics of molecules exposed to air. Here, we demonstrate the hyperspectral TERS imaging of single or a few brilliant cresyl blue (BCB) molecules at room temperature, along with quantitative spectral analyses. Robust chemical imaging is enabled by the freeze-frame approach using a thin Al2O3 capping layer, which suppresses spectral diffusions and inhibits chemical reactions and contamination in air. For the molecules resolved spatially in the TERS image, a clear Raman peak variation up to 7.5 cm-1 is observed, which cannot be found in molecular ensembles. From density functional theory-based quantitative analyses of the varied TERS peaks, we reveal the conformational heterogeneity at the single-molecule level. This work provides a facile way to investigate the single-molecule properties in interacting media, expanding the scope of single-molecule vibrational spectroscopy studies.

Purcell-enhanced photoluminescence of few-layer MoS2 transferred on gold nanostructure arrays with plasmonic resonance at the conduction band edge.

Plasmonic coupling of metallic nanostructures with two-dimensional molybdenum disulfide (MoS2) atomic layers is an important topic because it provides a pathway to manipulate the optoelectronic properties and to overcome the limited optical cross-section of the materials. Plasmonic enhanced light-matter interaction of a MoS2 layer is known to be mainly governed by optical field enhancement and the Purcell effect, while the discrimination of the contribution from each mechanism to the plasmonic enhancement is challenging. Here, we investigate photoluminescence (PL) enhancement from few-layer MoS2 transferred on Au nanostructure arrays with controlled localized surface plasmon resonance (LSPR) spectral positions that were detuned from the excitation wavelengths. Two distinctive regimes in LSPR mode-dependent PL enhancement were revealed showing a maximum enhancement (∼40-fold) with zero detuning and a modest enhancement (∼10-fold) with the red-shift detuned LSPR from the excitation wavelength, which were attributed to LSPR-induced optical field enhancement and the Purcell effect, respectively. By applying the experimental parameters into the Purcell effect formalism, an effective mode volume of ∼0.016λ03 was estimated. Our work provides an insight into how to utilize few-layer MoS2 as a base material for optoelectronics by harnessing Purcell-enhanced optical responsivity.

Fabrication of plasmonic arrays of nanodisks and nanotriangles by nanotip indentation lithography and their optical properties.

Fabrication of plasmonic nanostructures in a precise and reliable manner is a topic of huge interest because their structural details significantly affect their plasmonic properties. Herein, we present nanotip indentation lithography (NTIL) based on atomic force microscopy (AFM) indentation for the patterning of plasmonic nanostructures with precisely controlled size and shape. The size of the nanostructures is controlled by varying the indentation force of AFM tips into the mask polymer; while their shapes are determined to be nanodisks (NDs) or nanotriangles (NTs) depending on the shapes of the AFM tip apex. The localized surface plasmon resonance of the NDs is tailored to cover most of the visible-wavelength regime by controlling their size. The NTs show distinct polarization-dependent plasmon modes consistent with full-wave optical simulations. For the demonstration of the light-matter interaction control capability of NTIL nanostructures, we show that photoluminescence enhancement from MoS2 layers can be deliberately controlled by tuning the size of the nanostructures. Our results pave the way for the AFM-indentation-based fabrication of plasmonic nanostructures with a highly precise size and shape controllability and reproducibility.

Giant nonlinear optical responses from photon-avalanching nanoparticles.

Avalanche phenomena use steeply nonlinear dynamics to generate disproportionately large responses from small perturbations, and are found in a multitude of events and materials1. Photon avalanching enables technologies such as optical phase-conjugate imaging2, infrared quantum counting3 and efficient upconverted lasing4-6. However, the photon-avalanching mechanism underlying these optical applications has been observed only in bulk materials and aggregates6,7, limiting its utility and impact. Here we report the realization of photon avalanching at room temperature in single nanostructures-small, Tm3+-doped upconverting nanocrystals-and demonstrate their use in super-resolution imaging in near-infrared spectral windows of maximal biological transparency. Avalanching nanoparticles (ANPs) can be pumped by continuous-wave lasers, and exhibit all of the defining features of photon avalanching, including clear excitation-power thresholds, exceptionally long rise time at threshold, and a dominant excited-state absorption that is more than 10,000 times larger than ground-state absorption. Beyond the avalanching threshold, ANP emission scales nonlinearly with the 26th power of the pump intensity, owing to induced positive optical feedback in each nanocrystal. This enables the experimental realization of photon-avalanche single-beam super-resolution imaging7 with sub-70-nanometre spatial resolution, achieved by using only simple scanning confocal microscopy and without any computational analysis. Pairing their steep nonlinearity with existing super-resolution techniques and computational methods8-10, ANPs enable imaging with higher resolution and at excitation intensities about 100 times lower than other probes. The low photon-avalanching threshold and excellent photostability of ANPs also suggest their utility in a diverse array of applications, including sub-wavelength imaging7,11,12 and optical and environmental sensing13-15.

Nanorods with multidimensional optical information beyond the diffraction limit.

Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and diversity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here, we report a set of heterogeneous nanorods; each optically active section has its unique nonlinear response to donut-shaped illumination, so that one can discern each section with super-resolution. To achieve this, we first realize an approach of highly controlled epitaxial growth and produce a range of heterogeneous structures. Each section along the nanorod structure displays tunable upconversion emissions, in four optical dimensions, including color, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrate a 210 nm single nanorod as an extremely small polychromatic light source for the on-demand generation of RGB photonic emissions. This work benchmarks our ability toward the full control of sub-diffraction-limit optical diversities of single heterogeneous nanoparticles.

Effectual Labeling of Natural Killer Cells with Upconverting Nanoparticles by Electroporation for In Vivo Tracking and Biodistribution Assessment.

Natural killer (NK) cells, which are cytotoxic lymphocytes of the innate immune system and recognize cancer cells via various immune receptors, are promising agents in cell immunotherapy. To utilize NK cells as a therapeutic agent, their biodistribution and pharmacokinetics need to be evaluated following systemic administration. Therefore, in vivo imaging and tracking with efficient labeling and quantitative analysis of NK cells are required. However, the lack of the phagocytic capacity of NK cells makes it difficult to establish breakthroughs in cell labeling and subsequent in vivo studies. Herein, an effective labeling of upconverting nanoparticles (UCNPs) in NK cells is proposed using electroporation with high sensitivity and stability. The labeling performance of UCNPs functionalized with carboxy-polyethylene glycol (PEG) is better than with methoxy-PEG or with amine-PEG. The labeling efficiency becomes higher, but cell damage is greater as electric field increases; thus, there is an optimum electroporation condition for internalization of UCNPs into NK cells. The tracking and biodistribution imaging analyses of intravenously injected NK cells show that the labeled NK cells are initially distributed primarily in lungs and then spread to the liver and spleen. These advances will accelerate the application of NK cells as key components of immunotherapy against cancer.

Discrimination between target and non-target interactions on the viral surface by merging fluorescence emission into Rayleigh scattering.

Direct and quantitative determination of antibodies or cellular receptors dynamically binding to the surface of viral particles is the key issue for predicting the efficacy of therapeutic materials or host susceptibility to a new emerging pathogen. However, targeted visualization of infectious viruses is still highly challenging owing to their nanoscopic sizes and uncontrollable nonspecific interactions with loading molecules responsible for false signals. Here we present a multimodal single-molecule and single-particle (SMSP) visualization capable of simultaneously yet independently tracking Rayleigh scattering and fluorescence that, respectively, are generated from viruses (approximately 100 nm) and labeled interacting molecules. By analyzing real-time trajectories of fluorescent antibodies against a virus surface protein with reference to single virus-derived Rayleigh scattering, we determined heterogeneous binding stoichiometry of virus-antibody couplings irrespective of the nonspecific binder population. Therefore, our multimodal (or multi-level) SMSP assay visually identifies and selectively quantifies specific interactions between them with single binding event accuracy. As a 'specific-binding quantifier' to assess variable host susceptibility to a virus, it was further applied for distinguishing ratiometric bindings and spontaneous dissociation kinetics of synthesized isomeric receptors to influenza virus. The present framework could offer a solid analytical foundation for the development of a direct-acting antiviral agent inhibiting an integral viral enveloped protein and for nanobiological investigation for dissecting spatiotemporal nanoparticle-molecule interactions, which have been scarcely explored compared to those among plasmonic nanoparticles or among molecules only.

SERS-based particle tracking and molecular imaging in live cells: toward the monitoring of intracellular dynamics.

Although diverse endogenous biomolecules involved in life processes are of major interest in cell biology, there is still a lack of suitable methods for studying biomolecules within live cells without labelling. Herein, we describe a near-infrared (NIR) surface-enhanced Raman scattering (SERS)-based particle tracking technique gathering chemical information inside live cells for monitoring their intracellular dynamics. The wide-field SERS imaging spectroscopy system facilitates high temporal resolution (200 ms) under high spatial resolution (512 × 512 pixels) for one live cell. With high spatiotemporal resolution and signal-to-background ratio, we show that the Raman signal from intracellular cargoes in live cells is sporadically observed and localized to a vesicular level.

A smart tumor microenvironment responsive nanoplatform based on upconversion nanoparticles for efficient multimodal imaging guided therapy.

Near-infrared (NIR) light-induced imaging-guided cancer therapy has been studied extensively in recent years. Herein, we report a novel theranostic nanoplatform by modifying polyoxometalate (POM) nanoclusters onto mesoporous silica-coated upconversion nanoparticles (UCNPs), followed by loading doxorubicin (DOX) in the mesopores and coating a folate-chitosan shell onto the surface. In this nanoplatform, the core-shell structured UCNPs (NaYF4:Yb,Er@NaYF4:Yb,Nd) showed special upconverting luminescence (UCL) when irradiated with high-penetration 808 nm NIR light, and the doped Yb and Nd ions endowed the sample with CT imaging properties, thus achieving a dual-mode imaging function. Moreover, the simultaneously generated heat mediated by the 808 nm NIR light may coordinate with the chemotherapy generated from the released DOX to realize an efficient synergistic therapy, verified by diverse in vitro and in vivo assays. The coated folate-chitosan shell can target the platform to tumor tissues when it was transported in the blood vessels and accumulated in tumor sites via the enhanced permeability and retention effect (EPR). Due to the acidic and reductive microenvironment of the tumor, the DOX released quickly with the dissolved folate-chitosan shell, exhibiting obvious tumor microenvironment (TME) responsive properties. The smart imaging-guided therapeutic nanoplatform should be highly promising in TME responsive therapy.

Virus-mimetic polymer nanoparticles displaying hemagglutinin as an adjuvant-free influenza vaccine.

The generation of virus-mimetic nanoparticles has received much attention in developing a new vaccine for overcoming the limitations of current vaccines. Thus, a method, encompassing most viral features for their size, hydrophobic domain and antigen display, would represent a meaningful direction for the vaccine development. In the present study, a polymer-templated protein nanoball with direction oriented hemagglutinin1 on its surface (H1-NB) was prepared as a new influenza vaccine, exhibiting most of the viral features. Moreover, the concentrations of antigen on the particle surface were controlled, and its effect on immunogenicity was estimated by in vivo studies. Finally, H1-NB efficiently promoted H1-specific immune activation and cross-protective activities, which consequently prevented H1N1 infections in mice.

Fabrication and near-field visualization of a wafer-scale dense plasmonic nanostructured array.

Developing a sensor that identifies and quantifies trace amounts of analyte molecules is crucially important for widespread applications, especially in the areas of chemical and biological detection. By non-invasively identifying the vibrational signatures of the target molecules, surface-enhanced Raman scattering (SERS) has been widely employed as a tool for molecular detection. Here, we report on the reproducible fabrication of wafer-scale dense SERS arrays and single-nanogap level near-field imaging of these dense arrays under ambient conditions. Plasmonic nanogaps densely populated the spaces among globular Ag nanoparticles with an areal density of 120 particles per µm2 upon application of a nanolithography-free simple process consisting of the Ar plasma treatment of a polyethylene terephthalate substrate and subsequent Ag sputter deposition. The compact nanogaps produced a high SERS enhancement factor of 3.3 × 107 and homogeneous (coefficient of variation of 8.1%) SERS response. The local near fields at these nanogaps were visualized using photo-induced force microscopy that simultaneously enabled near-field excitation and near-field force detection under ambient conditions. A high spatial resolution of 3.1 nm was achieved. Taken together, the generation of a large-area SERS array with dense plasmonic nanogaps and the subsequent single-nanogap level characterization of the local near field have profound implications in the nanoplasmonic imaging and sensing applications.

Carboxymethyl dextran-based hypoxia-responsive nanoparticles for doxorubicin delivery.

In an attempt to develop the hypoxia-responsive nanoparticles for cancer therapy, a polymer conjugate, consisting of carboxymethyl dextran (CMD) and black hole quencher 3 (BHQ3), was prepared. The polymer conjugate can self-assemble into nanoparticles (CMD-BHQ3 NPs) under aqueous conditions. The anticancer drug, doxorubicin (DOX), was loaded in CMD-BHQ3 NPs to prepare DOX@CMD-BHQ3 NPs. The CMD-BHQ3 NPs released DOX in a sustained manner under physiological conditions, whereas the release rate of DOX remarkably increased under hypoxic conditions throughout the cleavage of the azo bond in BHQ3. In vitro cytotoxicity study revealed that DOX@CMD-BHQ3 NPs showed higher toxicity under hypoxic conditions than normoxic conditions. Confocal microscopic images indicated oxygen-dependent intracellular release of DOX from DOX@CMD-BHQ3. In vivo biodistribution study demonstrated that CMD-BHQ3 NPs were preferentially accumulated in the tumor after systemic administration into tumor-bearing mice. Overall, CMD-BHQ3 might be a promising carrier for selective drug release in the hypoxic tumor.