Welded Gold Nanoparticle Assemblies Defined Plasmonic Coupling.

Nanoparticle assemblies with interparticle ohmic contacts are crucial for nanodevice fabrication. Despite tremendous progress in DNA-programmable nanoparticle assemblies, seamlessly welding discrete components into welded continuous three-dimensional (3D) configurations remains challenging. Here, we introduce a single-stranded DNA-encoded strategy to customize welded metal nanostructures with tunable morphologies and plasmonic properties. We demonstrate the precise welding of gold nanoparticle assemblies into continuous metal nanostructures with interparticle ohmic contacts through chemical welding in solution. We find that the welded gold nanoparticle assemblies show a consistent morphology with welded efficiency over 90%, such as the rod-like, triangular, and tetrahedral metal nanostructures. Next, we show the versatility of this strategy by welding gold nanoparticle assemblies of varied sizes and shapes. Furthermore, the experiment and simulation show that the welded gold nanoparticle assemblies exhibit defined plasmonic coupling. This single-stranded DNA encoded welding system may provide a new route for accurately building functional plasmonic nanomaterials and devices.

Single-molecule localization microscopy at 2.4-fold resolution improvement with optical lattice pattern illumination.

Traditional camera-based single-molecule localization microscopy (SMLM), with its high imaging resolution and localization throughput, has made significant advancements in biological and chemical researches. However, due to the limitation of the fluorescence signal-to-noise ratio (SNR) of a single molecule, its resolution is difficult to reach to 5 nm. Optical lattice produces a nondiffracting beam pattern that holds the potential to enhance microscope performance through its high contrast and penetration depth. Here, we propose a new method named LatticeFLUX which utilizes the wide-field optical lattice pattern illumination for individual molecule excitation and localization. We calculated the Cramér-Rao lower bound of LatticeFLUX resolution and proved that our method can improve the single molecule localization precision by 2.4 times compared with the traditional SMLM. We propose a scheme using 9-frame localization, which solves the problem of uneven lattice light illumination. Based on the experimental single-molecule fluorescence SNR, we coded the image reconstruction software to further verify the resolution enhancement capability of LatticeFLUX on simulated punctate DNA origami, line pairs, and cytoskeleton. LatticeFLUX confirms the feasibility of using 2D structured light illumination to obtain high single-molecule localization precision under high localization throughput. It paves the way for further implementation of ultra-high resolution full 3D structured-light-illuminated SMLM.

Plasmonic Cavity-Catalysis by Standing Hot Carrier Waves.

Manipulating active sites of catalysts is crucial but challenging in catalysis science and engineering. Beyond the design of the composition and structure of catalysts, the confined electromagnetic field in optical cavities has recently become a promising method for catalyzing chemical reactions via strong light-matter interactions. Another form of confined electromagnetic field, the charge density wave in plasmonic cavities, however, still needs to be explored for catalysis. Here, we present an unprecedented catalytic mode based on plasmonic cavities, called plasmonic cavity-catalysis. We achieve direct control of catalytic sites in plasmonic cavities through standing hot carrier waves. Periodic catalytic hotspots are formed because of localized energy and carrier distribution and can be well tuned by cavity geometry, charge density, and excitation angle. We also found that the catalytic activity of the cavity mode increases several orders of magnitude compared with conventional plasmonic catalysis. We ultimately demonstrate that the locally concentrated long-lived hot carriers in the standing wave mode underlie the formation of the catalytic hotspots. Plasmonic cavity-catalysis provides a new approach to manipulate the catalytic sites and rates and may expand the frontier of heterogeneous catalysis.

DNA-Encoded Gold-Gold Wettability for Programmable Plasmonic Engineering.

Controlling the deposition and diffusion of adsorbed atoms (adatoms) on the surface of a solid material is vital for engineering the shape and function of nanocrystals. Here, we report the use of single-stranded DNA (oligo-adenine, oligo-A) to encode the wettability of gold seeds by homogeneous gold adatoms to synthesize highly tunable plasmonic nanostructures. We find that the oligo-A attachment transforms the nanocrystal growth mode from the classical Frank-van der Merwe to the Volmer-Weber island growth. Finely tuning the oligo-A density can continuously change the gold-gold contact angle (θ) from 35.1±3.6° to 125.3±8.0°. We further demonstrate the versatility of this strategy for engineering nanoparticles with different curvature and dimensions. With this unconventional growth mode, we synthesize a sub-nanometer plasmonic cavity with a geometrical singularity when θ>90°. Superfocusing of light in this nanocavity produces a near-infrared intraparticle plasmonic coupling, which paves the way to surface engineering of single-particle plasmonic devices.

Reactivating Catalytic Surface: Insights into the Role of Hot Holes in Plasmonic Catalysis.

Surface plasmon resonance of coinage metal nanoparticles is extensively exploited to promote catalytic reactions via harvesting solar energy. Previous efforts on elucidating the mechanisms of enhanced catalysis are devoted to hot electron-induced photothermal conversion and direct charge transfer to the adsorbed reactants. However, little attention is paid to roles of hot holes that are generated concomitantly with hot electrons. In this work, 13 nm spherical Au nanoparticles with small absorption cross-section are employed to catalyze a well-studied glucose oxidation reaction. Density functional theory calculation and X-ray absorption spectrum analysis reveal that hot holes energetically favor transferring catalytic intermediates to product molecules and then desorbing from the surface of plasmonic catalysts, resulting in the recovery of their catalytic activities. The studies shed new light on the use of the synergy of hot holes and hot electrons for plasmon-promoted catalysis.

Effects of donor and acceptor's fluorescence lifetimes on the method of applying Förster resonance energy transfer in STED microscopy.

Förster resonance energy transfer (FRET) probes being used to improve the resolution of stimulated emission depletion (STED) microscopy are numerically discussed. Besides the FRET efficiency and the excitation intensity, the fluorescence lifetimes of donor and acceptor are found to be another key parameter for the resolution enhancement. Using samples of FRET pairs with shorter donor lifetime and longer acceptor lifetime enhances the nonlinearity of the donor fluorescence, which leads to an increased resolution. The numerical simulation shows that a double resolution improvement of STED microscopy can be achieved by using Cy3-Atto647N samples when compared with that of using standard Cy3-only samples.

Light-Sheet Microscopic Imaging of Whole-Mouse Vascular Network with Fluorescent Microsphere Perfusion.

Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 µm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.

Programing Immunogenic Cell Death in Breast Tumors with Designer DNA Frameworks.

The low response rate and serious side effects of cancer treatment pose significant limitations in immunotherapy. Here, we developed a multifunctional tetrahedral DNA framework (TDF) as a drug carrier to recruit chemotherapeutants and trigger immunogenic cell death (ICD) effects, which could turn tumors from cold to hot to boost the efficacy of antitumor immunotherapy. A tumor-targeting peptide RGD was modified on the TDF to increase the delivery efficiency, and the chemotherapeutant doxorubicin (DOX) was loaded to induce ICD effects, which were assisted by the immune adjuvant of CpG immunologic sequences linked on TDF. We demonstrated that the multifunctional TDF could suppress 4T1 breast tumor growth by increasing tumor infiltration of CD8+ T cells, upregulating granzyme B and perforin expressions to twice as much as the control group, and decreasing 30% CD25+ Treg cells. Furthermore, the combination of α-PD-1 could inhibit the growth of distant tumor and suppressed tumor recurrence in a bilateral syngeneic 4T1 mouse model; the distant tumor weight inhibition rate was about 91.6%. Hence, through quantitatively targeting the delivery of DOX to reduce the side effects of chemotherapy and sensitizing the immune response by ICD effects, this multifunctional TDF therapeutic strategy displayed better treatment effect and a promising clinical application prospect.

DNA-PAINT Super-Resolution Imaging for Characterization of Nucleic Acid Nanostructures.

Numerous nucleic acid nanostructures of unique addressability and programmability have been fabricated for emerging applications. Structural characterization with atomic force microscopy and electron microscopy can provide information on the structural morphology and precision of these nanostructures. However, either structural information of native nucleic acid nanostructures in hydrated environment or the availability of addressable sites on these nanostructures could not be determined. Alternatively, DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) enables direct optical visualization of nucleic acid nanostructures in native forms, as well as evaluation of the accessibility of addressable sites on them. In this Review, the working principle of DNA-PAINT is introduced, followed by the summary on advances of DNA-PAINT characterization of various nucleic acid nanostructures. Finally, the current challenges and prospects for DNA-PAINT characterization are presented. We envision DNA-PAINT to be a potent characterization tool for functional nanomaterials.

Super-resolution plasmonic imaging via scattering saturation STED.

Based on the nonlinear plasmonic scattering response to the modulated excitation in time, we realized a single-wavelength super-resolution imaging method on a custom-built system which is named as a scattering saturation STED (ssSTED) microscope. A spatial resolution of λ/7 (65 nm) was obtained on 50 nm gold nanoparticles.

Spaser Nanoparticles for Ultranarrow Bandwidth STED Super-Resolution Imaging.

Super-resolution microscopy, as a powerful tool of seeing abundant spatial details, typically can only distinguish a few distinct targets at a time due to the spectral crosstalk between fluorophores. Spaser (i.e., surface plasmon laser) nanoprobes, which confine lasing emission into nanoscale, offer an opportunity to eliminate such obstacle. Here, realized is narrow band stimulated emission depletion (STED) nanoscopy on spaser nanoparticles by collecting the coherent spasing signals. Demonstrated are the physics concept and feasibility of erasing spaser emission by using a depletion beam to suppress the population inversion, which lays the foundation of spaser-based STED super-resolution. Thanks to the small size (47 nm) and narrow spectral linewidth (3.8 nm) of the spaser nanoparticles, a 74 nm spatial resolution in STED imaging within an acquisition bandwidth of 10 nm is finally obtained. These spaser nanoparticles, if multiplexing with different wavelengths, in principle, allow for spectral-multiplexed imaging, sensing, cytometry, and light operation of a large number of targets all at once.

Revealing transient events of molecular recognition via super-localization imaging of single-particle motion.

Molecular recognition plays an important role in biological systems and relates to a wide range of applications in disease diagnostics and therapeutics. Studies based on steady state or ensemble analysis may mask critical dynamic information of single recognition events. Here we report a study of monitoring the transient molecular recognition via single particle motion. We utilized a super-localization imaging methodology, to comprehensively evaluate the rotational Brownian motion of a single nanoparticle in spatial-temporal-frequential domain, with a spatial accuracy ~20 nm and a temporal resolution of ~10 ms. The transient moment of molecular encountering was captured and different binding modes were discriminated. We observed that the transient recognition events were not static states of on or off, but stochastically undergoes dynamical transformation between different binding modes. This study improves our understanding about the dynamic nature of molecular recognition events beyond the ensemble characterization via binding constant.