A scalable fabrication method for gold nanodisk-upconverting nanoparticle hybrid nanostructures.

Plasmonic nanostructures can be used to enhance the efficiency of upconversion nanoparticles (UCNPs) and enable new functionalities. However, the fabrication of these hybrid plasmon-UCNP nanostructures has traditionally relied on either wet chemistry or nanolithography routes that are difficult to control, scale up, or both. In this work, we present a scalable nanofabrication process, capable of producing a massive array of gold-UCNP hybrid nanostructures over a few mm2 area and with excellent uniformity in the photoluminescence intensity. This new approach combines the scalability of the bottom-up self-assembly method and the precision of the top-down nanolithography approach. It provides an efficient alternative route for the production of plasmonically enhanced UCNPs. A detailed discussion on the optimization of the UCNP self-assembly, the gold nanodisk lithography, and the nanopattern transfer processes is presented here. Additionally, we showcase the potential of this new approach for fabricating mechanical force sensors based on the selective plasmonic enhancement of the UCNP emission. This new approach holds great potential in facilitating the production of plasmonically enhanced UCNPs that can be deployed for both imaging and sensing applications.

On-chip mid-infrared optical sensing with GeSbSe waveguides and resonators.

We fabricated single mode Ge28Sb12Se60 waveguides and resonators using e-beam lithography and achieved a propagation loss of 3.88 dB/cm at 3.66 µm. We compared BCl3 and CHF3 etch chemistries and determined CHF3 produced 1.5 dB/cm higher propagation losses at 3.6 µm due to C-H bond absorption. We use fabricated waveguides to detect an aromatic aldehyde dissolved in a non-polar solvent with a limit of detection of 1.09 µmol/mL. We then reduce this detection limit to 0.25 µmol/mL using the enhancement produced by a chalcogenide ring resonator.

Fabrication and characterization of high quality GeSbSe reflowed and etched ring resonators.

We demonstrate the fabrication of high Q Ge28Sb12Se60 ring resonators in an all chalcogenide platform through electron-beam lithography, lift-off and thermal reflow. We achieve a Q factor of (3.9 ± 0.2) × 105 in the reflowed ring resonators and (2.5 ± 0.2) × 105 in the reactive ion etched ring resonators at 1550 nm. We measure the line roughness of these devices to estimate the scattering loss. We determine the material and scattering losses of the waveguide and find an additional 1.1 dB/cm excess loss from surface absorption. We fabricate Ge23Sb7S70 waveguides with 0.6 dB/cm of losses and show that Ge23Sb7S70 waveguides do not experience the same kind of excess loss when fabricated under the same conditions. This indicates the excess loss is related to the chemical composition of Ge28Sb12Se60 compound.

Enzyme Prodrug Therapy with Photo-Cross-Linkable Anti-EGFR Affibodies Conjugated to Upconverting Nanoparticles.

In this work, we demonstrate that a photo-cross-linkable conjugate of upconverting nanoparticles and cytosine deaminase can catalyze prodrug conversion specifically at tumor sites in vivo. Non-covalent association of proteins and peptides with cellular surfaces leads to receptor-mediated endocytosis and catabolic degradation. Recently, we showed that covalent attachment of proteins such as affibodies to cell receptors yields extended expression on cell surfaces with preservation of protein function. To adapt this technology for in vivo applications, conjugates were prepared from upconverting nanoparticles and fusion proteins of affibody and cytosine deaminase enzyme (UC-ACD). The affibody allows covalent photo-cross-linking to epidermal growth factor receptors (EGFRs) overexpressed on Caco-2 human colorectal cancer cells under near-infrared (NIR) light. Once bound, the cytosine deaminase portion of the fusion protein converts the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU). NIR covalent photoconjugation of UC-ACD to Caco-2 cells showed 4-fold higher retention than observed with cells that were not irradiated in vitro. Next, athymic mice expressing Caco-2 tumors showed 5-fold greater UC-ACD accumulation in the tumors than either conjugates without the CD enzyme or UC-ACDs in the absence of NIR excitation. With oral administration of 5-FC prodrug, tumors with photoconjugated UC-ACD yielded 2-fold slower growth than control groups, and median mouse survival increased from 28 days to 35 days. These experiments demonstrate that enzyme-decorated nanoparticles can remain viable after a single covalent photoconjugation in vivo, which can in turn localize prodrug conversion to tumor sites for multiple weeks.

True FRET-based sensing of pH via Separation of FRET and Photon Reabsorption.

Förster Resonance Energy Transfer (FRET)-based devices have been extensively researched as potential biosensors due to their highly localized responsivity. In particular, dye-conjugated upconverting nanoparticles (UCNPs) are among the most promising FRET-based sensor candidates. UCNPs have a multi-modal emission profile that allows for ratiometric sensing, and by conjugating a biosensitive dye to their surface, this profile can be used to measure localized variations in biological parameters. However, the complex nature of the UCNP energy profile as well as reabsorption of emitted photons must be taken into account in order to properly sense the target parameters. To our knowledge, no proposed UCNP-based sensor has accurately taken care of these intricacies. In this article, we account for these complexities by creating a FRET-based sensor that measures pH. This sensor utilizes Thulium ( Tm 3 + )-doped UCNPs and the fluorescent dye Fluorescein Isothiocyanate (FITC). We first demonstrate that photon reabsorption is a serious issue for the 475 nm Tm 3 + emission, thereby limiting its use in FRET-based sensing. We then show that by taking the ratio of the 646 and 800 nm emissions rather than the more popular 475 nm one, we are able to measure pH exclusively through FRET.

Selective enhancement of upconversion luminescence for enhanced ratiometric sensing.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted widespread interest in bioimaging and sensing due to their photostability, low excitation energy, and good tissue penetration. Plasmonic nanostructures, on the other hand, can enhance the luminescence of UCNPs by concentrating electric fields into a nanoscale volume. While the enhanced luminescence intensity is in principle beneficial to sensing, intensity-based sensing has limitations in absolute measurements. This deficiency can be overcome by employing ratiometric sensing in which intensity ratio, rather than intensity itself, is used to quantitatively determine the presence of analytes. The ratiometric sensing is advantageous because the intensity ratio is much less sensitive to the variations in the environment and the number of probe materials in the sensing volume. Here, we demonstrate a plasmonic nanostructure with upconversion nanoparticles for an enhanced ratiometric sensing platform. The plasmonic nanostructure is composed of UCNPs, an indium tin oxide (ITO) spacer layer and an Au nanodisk. The nanostructure is designed such that the plasmon resonance selectively enhances the red luminescence of NaYGdF4:Yb3+, Er3+ UCNPs while leaving the green luminescence unaffected, thereby increasing the dynamic range and achievable sensitivity of the red-to-green (R/G) intensity ratio. We observed a 4-fold enhancement in the R/G ratio and also a drastic reduction in the signal uncertainty. This work advances our knowledge of the optical interaction between UCNPs and plasmonic nanostructures and also provides a foundation for improved ratiometric sensing in biomedical applications.

High-Efficiency Solar Vapor Generation Boosted by a Solar-Induced Updraft with Biomimetic 3D Structures.

Sunlight-based desalination is one of the most environment-friendly, low-cost methods for obtaining freshwater on the planet. We implemented a biomimetic three-dimensional (3D) solar evaporator, improved by a solar-induced air-flow updraft. A carbon-coated polyvinyl alcohol (PVA) foam allowed us to achieve perfect absorption of ultrabroadband sunlight and continuously provide water to tall 3D structures. Integrating the convection flower (Amorphophallus titanum) and solar chimney structure, we proposed a bio-inspired 3D solar evaporator system that generates an updraft airflow. This updraft replaces saturated vapor between neighboring PVA foams with dry air, resulting in a significant increase in the effectiveness of dry air-water contact interfaces. Under the 1 sun condition (1 kW m-2), we achieve a high solar-vapor conversion efficiency of 95.9%.

Selective excitation of plasmon resonances with single V-point cylindrical vector beams.

We use a rigorous group theoretical method to identify a class of cylindrical vector beams that can selectively excite the plasmon modes of axially symmetric plasmonic structures. Our choice of the single V-point cylindrical vector beams as the basis to decompose cylindrical beams dramatically simplifies the symmetry analysis in the group theory framework. With numerical simulations, we demonstrate that any plasmon eigenmodes, bright or dark, can be selectively excited individually or jointly. A straightforward protocol to get access to the desired plasmon mode using symmetry coupling is presented.

Third-harmonic generation enhancement in an ITO nanoparticle-coated microresonator.

We report a ∼3-fold enhancement of third-harmonic generation (THG) conversion efficiency using indium tin oxide (ITO) nanoparticles on the surface of an ultra-high-Q silica microsphere. This is one of the largest microcavity-based THG enhancements reported. Phase-matching and spatial mode overlap are explored numerically to determine the microsphere radius (∼29 µm) and resonant mode numbers that maximize THG. Furthermore, the ITO nanoparticles are uniformly bonded to the cavity surface by drop-casting, eliminating the need for complex fabrication. The significant improvement in THG conversion efficiency establishes functionalized ITO microcavities as a promising tool for broadband frequency conversion, nonlinear enhancement, and applications in integrated photonics.

Enhancement of third-order nonlinearity of thermally evaporated GeSbSe waveguides through annealing.

Chalcogenides are a promising platform for infrared nonlinear optics but are susceptible to structural changes during fabrication that affect their linear and nonlinear optical properties. We analyze the structure and optical properties of thermally evaporated and annealed chalcogenide films. Thermally evaporated Ge28Sb12Se60 has an increased selenium content, bandgap, and concentration of heteropolar bonds. The concentration of heteropolar bonds can be reduced by annealing above the glass transition temperature, resulting in improved optical nonlinearity. We demonstrate a 4-fold enhancement of third-order nonlinearity in Ge28Sb12Se60 chalcogenide waveguides by thermal annealing and a decrease in propagation loss from 2.5 dB/cm to 1 dB/cm as an added benefit.

Recent insights into upconverting nanoparticles: spectroscopy, modeling, and routes to improved luminescence.

The development of reliable and reproducible synthetic routes that produce monodisperse lanthanide-doped upconverting nanoparticles has resulted in an appreciable need to determine the mechanisms which govern upconversion luminescence at the nanoscale. New experimental and theoretical evidence explicates the quenching phenomena involved in the low luminescence efficiencies. A deeper understanding of the role of surfaces and defects in the quenching mechanisms and the properties of upconverting nanoparticles are of fundamental importance to develop nanomaterials with enhanced luminescence properties. Herein, we summarize the most recent spectroscopic investigations, which have enabled the scientific community to ascertain that the predominant source of quenching involved in the luminescence of lanthanide-doped upconverting nanoparticles can be attributed to surface-defects. Modeling of these mechanisms in nanomaterials supports the experimental findings and yields further insights into the surface phenomena, providing a predictive tool to improve the luminescent efficiencies in nanomaterials.

Single gold-bridged nanoprobes for identification of single point DNA mutations.

Consensus ranking of protein affinity to identify point mutations has not been established. Therefore, analytical techniques that can detect subtle variations without interfering with native biomolecular interactions are required. Here we report a rapid method to identify point mutations by a single nanoparticle sensing system. DNA-directed gold crystallization forms rod-like nanoparticles with bridges based on structural design. The nanoparticles enhance Rayleigh light scattering, achieving high refractive-index sensitivity, and enable the system to monitor even a small number of protein-DNA binding events without interference. Analysis of the binding affinity can compile an atlas to distinguish the potential of various point mutations recognized by MutS protein. We use the atlas to analyze the presence and type of single point mutations in BRCA1 from samples of human breast and ovarian cancer cell lines. The strategy of synthesis-by-design of plasmonic nanoparticles for sensors enables direct identification of subtle biomolecular binding distortions and genetic alterations.

Air-like plasmonics with ultralow-refractive-index silica aerogels.

The coupling of the surface plasmon near-field into the sensing medium is key to the sensitivity of surface plasmon-based sensing devices. A low-index dielectric is necessary for the sensing medium to support a highly-penetrating surface plasmon evanescent field that extends well into the dielectric medium. The air-like refractive index, n, of an aerogel substrate provides another dimension for ultralow-index plasmonic devices. In this paper, we experimentally observed an angular surface plasmon resonance dip at 74° with the ultralow-index aerogel substrate, as was expected from theory. We also demonstrated the comparatively high-sensitivity surface plasmon resonance wavelength, λ, while the change in Δλ/Δn with different substrates was studied in detail. A 740 nm-period metal grating was imprinted on aerogel (n = 1.08) and polydimethylsiloxane (PDMS; n = 1.4) substrates. The ultraviolet-visible-near-infrared spectra were observed in the reflection mode on the grating, resulting in sensitivities of 740.2 and 655.9 nm/RIU for the aerogel and PDMS substrates, respectively. Numerical simulations were performed to understand the near-field of the surface plasmon, which demonstrated resonances well correlated with the experimentally observed results. The near-field due to excitation of the surface plasmon polaritons is observed to be more confined and to penetrate deeper into the sensing medium when a low-index substrate is used.

Multifunctional nanoclusters of NaYF4:Yb3+,Er3+ upconversion nanoparticle and gold nanorod for simultaneous imaging and targeted chemotherapy of bladder cancer.

This paper reports successful synthesis of multifunctional nanoclusters of upconversion nanoparticle (UCNP) and gold nanorod (AuNR) through a PEGylation process. UCNPs emit visible luminescence under near-infrared excitation, producing high-contrast images with no background fluorescence. When coupled with AuNRs, the resulting UCNP-AuNR multifunctional nanoclusters are capable of simultaneous detection and treatment of bladder cancer. These UCNP-AuNR nanoclusters are further functionalized with antibodies to epidermal growth factor receptor (EGFR) to target bladder cancer cells known to overexpress EGFRs. This paper demonstrates, for the first time, efficient targeting of bladder cancer cells with UCNP-AuNR nanoclusters. In addition to high-contrast imaging and consequently high sensitivity detection of bladder cancer cells, highly selective optoporation-assisted chemotherapy was accomplished using a dosage of chemotherapy agent significantly lower than any previous reports, within a clinically relevant incubation time window. These results are highly relevant to the eventual human application in which the nanoclusters and chemotherapy drugs will be directly instilled in bladder via urinary catheter.

Over 1000-fold enhancement of upconversion luminescence using water-dispersible metal-insulator-metal nanostructures.

Rare-earth activated upconversion nanoparticles (UCNPs) are receiving renewed attention for use in bioimaging due to their exceptional photostability and low cytotoxicity. Often, these nanoparticles are attached to plasmonic nanostructures to enhance their photoluminescence (PL) emission. However, current wet-chemistry techniques suffer from large inhomogeneity and thus low enhancement is achieved. In this paper, we report lithographically fabricated metal-insulator-metal (MIM) nanostructures that show over 1000-fold enhancement of their PL. We demonstrate the potential for bioimaging applications by dispersing the MIMs into water and imaging bladder cancer cells with them. To our knowledge, our results represent one and two orders of magnitude improvement, respectively, over the best lithographically fabricated structures and colloidal systems in the literature. The large enhancement will allow for bioimaging and therapeutics using lower particle densities or lower excitation power densities, thus increasing the sensitivity and efficacy of such procedures while decreasing potential side effects.

Large-scale nanoporous metal-coated silica aerogels for high SERS effect improvement.

We investigate the optical properties and surface-enhanced Raman scattering (SERS) characteristics of metal-coated silica aerogels. Silica aerogels were fabricated by easily scalable sol-gel and supercritical drying processes. Metallic nanogaps were formed on the top surface of the nanoporous silica network by controlling the thickness of the metal layer. The optimized metallic nanogap structure enabled strong confinement of light inside the gaps, which is a suitable property for SERS effect. We experimentally evaluated the SERS enhancement factor with the use of benzenethiol as a probe molecule. The enhancement factor reached 7.9 × 107 when molecules were adsorbed on the surface of the 30 nm silver-coated aerogel. We also theoretically investigated the electric field distribution dependence on the structural geometry and substrate indices. On the basis of FDTD simulations, we concluded that the electric field was highly amplified in the vicinity of the target analyte owing to a combination of the aerogel's ultralow refractive index and the high-density metallic nanogaps. The aerogel substrate with metallic nanogaps shows great potential for use as an inexpensive, highly sensitive SERS platform to detect environmental and biological target molecules.

Anti-EGFR Affibodies with Site-Specific Photo-Cross-Linker Incorporation Show Both Directed Target-Specific Photoconjugation and Increased Retention in Tumors.

A significant challenge for solid tumor treatment is ensuring that a sufficient concentration of therapeutic agent is delivered to the tumor site at doses that can be tolerated by the patient. Biomolecular targeting can bias accumulation in tumors by taking advantage of specific interactions with receptors overexpressed on cancerous cells. However, while antibody-based immunoconjugates show high binding to specific cells, their low dissociation constants ( KD) and large Stokes radii hinder their ability to penetrate deep into tumor tissue, leading to incomplete cell killing and tumor recurrence. To address this, we demonstrate the design and production of a photo-cross-linkable affibody that can form a covalent bond to epidermal growth factor receptor (EGFR) under near UV irradiation. Twelve cysteine mutations were created of an EGFR affibody and conjugated with maleimide-benzophenone. Of these only one exhibited photoconjugation to EGFR, as demonstrated by SDS-PAGE and Western blot. Next this modified affibody was shown to not only bind EGFR expressing cells but also show enhanced retention in a 3D tumor spheroid model, with minimal loss up to 24 h as compared to either unmodified EGFR-binding affibodies or nonbinding, photo-cross-linkable affibodies. Finally, in order to show utility of photo-cross-linking at clinically relevant wavelengths, upconverting nanoparticles (UCNPs) were synthesized that could convert 980 nm light to UV and blue light. In the presence of UCNPs, both direct photoconjugation to EGFR and enhanced retention in tumor spheroids could be obtained using near-infrared illumination. Thus, the photoactive affibodies developed here may be utilized as a platform technology for engineering new therapy conjugates that can penetrate deep into tumor tissue and be retained long enough for effective tumor therapy.

Material-Versatile Ultrabroadband Light Absorber with Self-Aggregated Multiscale Funnel Structures.

Broadband light absorbers are essential components for a variety of applications, including energy harvesting and optoelectronic devices. Thus, the development of a versatile absorbing structure that is applicable in various operating environments is required. In this study, a material-versatile ultrabroadband absorber consisting of metal-coated self-aggregated Al2O3 nanowire bundles with multiscale funnel structures is fabricated. A high absorptance of ∼0.9 over the AM 1.5G spectrum (300-2500 nm) is realized for absorbers with a range of metal coatings, including Al, W, and titanium nitride (TiN). We demonstrate that the plasmonic nanofocusing and index-matching effects of the funnel structure result in strong ultrabroadband absorption for the various metal coatings, even though the coating materials have different optical properties. As an example of applicability in an operating environment, in the evaluation of the thermal-oxidation resistance, the Al-coated solar absorber exhibits superior performance to those coated with refractory materials such as W and TiN because of the protective alumina layer formed on the Al surface.

TiO2-Capped Gold Nanorods for Plasmon-Enhanced Production of Reactive Oxygen Species and Photothermal Delivery of Chemotherapeutic Agents.

Near infrared (NIR)-absorbing noble metal nanostructures are being extensively studied as theranostic agents, in particular for photoacoustic imaging and photothermal therapy. Because of the electric field enhancement at the tips of anisotropic metal nanostructures, positioning photoactive species at these sites can lead to increased energy absorption. Herein, we show the site-specific placement of NIR-active photosensitizers at the ends of gold nanorods (AuNRs) by growing porous TiO2 caps. The surface plasmon resonance of the AuNRs was carefully tuned to overlap with the exciton absorption of indocyanine green (ICG), a NIR photosensitizer with low quantum yields and poor photostability. In conjugating high amounts of ICG to the TiO2 caps, increased amounts of singlet oxygen (1O2) were generated as compared to when ICG was attached to sidewalls of the AuNRs. Because the AuNRs also cause local increases in temperature upon NIR excitation, DNA strands were next attached to the AuNRs sidewalls and loaded with doxorubicin (DOX). We found that the synergistic effect of increased 1O2 and photothermal-induced drug delivery led to significant improvements in tumor cell killing. This work demonstrates that with careful design over hybrid nanostructure synthesis, higher levels of tumor therapy may be achieved.

Cage-templated synthesis of highly stable palladium nanoparticles and their catalytic activities in Suzuki-Miyaura coupling.

We report the controlled synthesis of small palladium nanoparticles (PdNPs) with narrow particle size distribution (1.8 ± 0.2 nm) using an organic molecular cage as a template. The well-defined cage structure and thioether anchoring groups inside the cavity are critical for the formation of narrowly distributed PdNPs, offering a confined organic molecular environment and guiding PdNP nucleation and growth. The resulting encapsulated PdNPs are resistant to agglomeration and stable in solution exposed to air at room temperature. When provided with a protective cage shell with minimum surface coverage, such PdNPs are capable of catalyzing organic reactions, showing high catalytic activity in Suzuki-Miyaura coupling reactions.