Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

Quantum Dot Patterning and Encapsulation by Maskless Lithography for Display Technologies.

For their unique optical properties, quantum dots (QDs) have been extensively used as light emitters in a number of photonic and optoelectronic applications. They even met commercialization success through their implementation in high-end displays with unmatched brightness and color rendering. For such applications, however, QDs must be shielded from oxygen and water vapor, which are known to degrade their optical properties over time. Even with highly qualitative QDs, this can only be achieved through their encapsulation between barrier layers. With the emergence of mini- and microLED for higher contrast and miniaturized displays, new strategies must be found for the concomitant patterning and encapsulation of QDs, with sub-millimeter resolution. To this end, we developed a new approach for the direct patterning of QDs through maskless lithography. By combining QDs in photopolymerizable resins with digital light processing (DLP) projectors, we developed a versatile and massively parallel fabrication process for the additive manufacturing of functional structures that we refer to as QD pockets. These 3D heterostructures are designed to provide isotropic encapsulation of the QDs, and hence prevent edge ingress from the lateral sides of QD films, which remains a shortcoming of the current technologies.

A Comparative Study of the Band-Edge Exciton Fine Structure in Zinc Blende and Wurtzite CdSe Nanocrystals.

In this paper, we studied the role of the crystal structure in spheroidal CdSe nanocrystals on the band-edge exciton fine structure. Ensembles of zinc blende and wurtzite CdSe nanocrystals are investigated experimentally by two optical techniques: fluorescence line narrowing (FLN) and time-resolved photoluminescence. We argue that the zero-phonon line evaluated by the FLN technique gives the ensemble-averaged energy splitting between the lowest bright and dark exciton states, while the activation energy from the temperature-dependent photoluminescence decay is smaller and corresponds to the energy of an acoustic phonon. The energy splittings between the bright and dark exciton states determined using the FLN technique are found to be the same for zinc blende and wurtzite CdSe nanocrystals. Within the effective mass approximation, we develop a theoretical model considering the following factors: (i) influence of the nanocrystal shape on the bright-dark exciton splitting and the oscillator strength of the bright exciton, and (ii) shape dispersion in the ensemble of the nanocrystals. We show that these two factors result in similar calculated zero-phonon lines in zinc blende and wurtzite CdSe nanocrystals. The account of the nanocrystals shape dispersion allows us to evaluate the linewidth of the zero-phonon line.

Quantum dot lasing from a waterproof and stretchable polymer film.

Colloidal quantum dots (QDs) are excellent optical gain materials that combine high material gain, a strong absorption of pump light, stability under strong light exposure and a suitability for solution-based processing. The integration of QDs in laser cavities that fully exploit the potential of these emerging optical materials remains, however, a challenge. In this work, we report on a vertical cavity surface emitting laser, which consists of a thin film of QDs embedded between two layers of polymerized chiral liquid crystal. Forward directed, circularly polarized defect mode lasing under nanosecond-pulsed excitation is demonstrated within the photonic band gap of the chiral liquid crystal. Stable and long-term narrow-linewidth lasing of an exfoliated free-standing, flexible film under water is obtained at room temperature. Moreover, we show that the lasing wavelength of this flexible cavity shifts under influence of pressure, strain or temperature. As such, the combination of solution processable and stable inorganic QDs with high chiral liquid crystal reflectivity and effective polymer encapsulation leads to a flexible device with long operational lifetime, that can be immersed in different protic solvents to act as a sensor.

General Expression for the Size-Dependent Optical Properties of Quantum Dots.

While initial theories on quantum confinement in colloidal quantum dots (QDs) led to analytical band gap/size relations or sizing functions, numerical methods describe size quantization more accurately. However, because of the lack of reliable sizing functions, researchers fit experimental band gap/size data sets using models with redundant, physically meaningless parameters that break down upon extrapolation. Here, we propose a new sizing function based on a proportional correction for nonparabolic bands. Using known bulk parameters, we predict size quantization for groups IV, III-V, II-VI, and IV-VI and metal-halide perovskite semiconductors, including straightforward adaptations for negative-gap semiconductors and nonspherical QDs. Refinement with respect to experimental data is possible using the Bohr diameter as a fitting parameter, by which we show a statistically relevant difference in the band gap/size relation for wurtzite and zinc blende CdSe. The general sizing function proposed here unifies the QD size calibration and enables researchers to assess bulk semiconductor parameters and predict the size quantization in unexplored materials.

Porous cage-derived nanomaterial inks for direct and internal three-dimensional printing.

The convergence of 3D printing techniques and nanomaterials is generating a compelling opportunity space to create advanced materials with multiscale structural control and hierarchical functionalities. While most nanoparticles consist of a dense material, less attention has been payed to 3D printing of nanoparticles with intrinsic porosity. Here, we combine ultrasmall (about 10 nm) silica nanocages with digital light processing technique for the direct 3D printing of hierarchically porous parts with arbitrary shapes, as well as tunable internal structures and high surface area. Thanks to the versatile and orthogonal cage surface modifications, we show how this approach can be applied for the implementation and positioning of functionalities throughout 3D printed objects. Furthermore, taking advantage of the internal porosity of the printed parts, an internal printing approach is proposed for the localized deposition of a guest material within a host matrix, enabling complex 3D material designs.

Two-Dimensional Superstructures of Silica Cages.

Despite extensive studies on mesoporous silica since the early 1990s, the synthesis of two-dimensional (2D) silica nanostructures remains challenging. Here, mesoporous silica is synthesized at an interface between two immiscible solvents under conditions leading to the formation of 2D superstructures of silica cages, the thinnest mesoporous silica films synthesized to date. Orientational correlations between cage units increase with increasing layer number controlled via pH, while swelling with oil and mixed surfactants increase micelle size dispersity, leading to complex clathrate type structures in multilayer superstructures. The results suggest that a three-dimensional (3D) crystallographic registry within cage-like superstructures emerges as a result of the concerted 3D co-assembly of the organic and inorganic components. Mesoporous 2D superstructures can be fabricated over macroscopic film dimensions and stacked on top of each other. The realization of previously inaccessible mesoporous silica heterostructures with separation or catalytic properties unachievable via conventional bulk syntheses is envisioned.

Efficient Endocytosis of Inorganic Nanoparticles with Zwitterionic Surface Functionalization.

PEGylation, which has traditionally been the method of choice to enhance the colloidal stability of nanostructures designed for biological applications and to prevent nonspecific protein adsorption, is now being challenged by short zwitterionic ligands. Inspired by the zwitterionic nature of cell membranes, these ligands have the potential to push forward the field of nanoparticles for nanomedicine. In this work, we report a thorough analysis of the surface chemistry of silica-coated luminescent CdSe/CdS quantum dots functionalized with either PEG-silane or zwitterionic sulfobetaine-silane by quantitative nuclear magnetic resonance spectroscopy. We demonstrate the differences in the cellular uptake propensity between particles with these two ligands. Although both ligands offer good colloidal stability in a crowded cell culture medium, the zwitterionic-functionalized nanoparticles with an optimized ligand density showed to be more easily endocytosed by HeLa cells. This approach can readily be transferred to other nanoparticle systems offering a wealth of unique properties, with great potential for intracellular bioapplications.

Early Formation Pathways of Surfactant Micelle Directed Ultrasmall Silica Ring and Cage Structures.

By combining a surfactant, an organic pore expander, a silane, and poly(ethylene glycol) (PEG), we have observed the formation of a previously unknown set of ultrasmall silica structures in aqueous solutions. At appropriate concentrations of reagents, ∼2 nm primary silica clusters arrange around surfactant micelles to form ultrasmall silica rings, which can further evolve into cage-like structures. With increasing concentration, these rings line up into segmented worm-like one-dimensional (1D) structures, an effect that can be dramatically enhanced by PEG addition. PEG adsorbed 1D striped cylinders further arrange into higher order assemblies in the form of two-dimensional (2D) sheets or three-dimensional (3D) helical structures. Results provide insights into synergies between deformable noncovalent organic molecule assemblies and covalent inorganic network formation as well as early transformation pathways from spherical soft materials into 1D, 2D, and 3D silica solution structures, hallmarks of mesoporous silica materials formation. The ultrasmall silica ring and cage structures may prove useful in nanomedicine and other nanotechnology based applications.

The Impact of Core/Shell Sizes on the Optical Gain Characteristics of CdSe/CdS Quantum Dots.

Colloidal quantum dots (QDs) are highly attractive as the active material for optical amplifiers and lasers. Here, we address the relation between the structure of CdSe/CdS core/shell QDs, the material gain they can deliver, and the threshold needed to attain net stimulated emission by optical pumping. On the basis of an initial gain model, we predict that reducing the thickness of the CdS shell grown around a given CdSe core will increase the maximal material gain, while increasing the shell thickness will lower the gain threshold. We assess this trade-off by means of transient absorption spectroscopy. Our results confirm that thin-shell QDs exhibit the highest material gain. In quantitative agreement with the model, core and shell sizes hugely impact on the material gain, which ranges from 2800 cm-1 for large core/thin shell QDs to less than 250 cm-1 for small core/thick shell QDs. On the other hand, the significant threshold reduction expected for thick-shell QDs is absent. We relate this discrepancy between model and experiment to a transition from attractive to repulsive exciton-exciton interactions with increasing shell thickness. The spectral blue-shift that comes with exciton-exciton repulsion leads to competition between stimulated emission and higher energy absorbing transitions, which raises the gain threshold. As a result, small-core/thick-shell QDs need up to 3.7 excitations per QD to reach transparency, whereas large-core/thin shell QDs only need 1.0, a number often seen as a hard limit for biexciton-mediated optical gain. This makes large-core/thin-shell QDs that feature attractive exciton-exciton interactions the overall champion core/shell configuration in view of highest material gain, lowest threshold exciton occupation, and longest gain lifetime.

Publisher Correction: Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles.

Change history: In Fig. 3b of this Letter, the labels for the outer (11.8 nm) and inner (7.4 nm) diameters of the structure were inadvertently omitted. Fig. 3 has been corrected online.

Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles.

Nanometre-sized objects with highly symmetrical, cage-like polyhedral shapes, often with icosahedral symmetry, have recently been assembled from DNA1-3, RNA 4 or proteins5,6 for applications in biology and medicine. These achievements relied on advances in the development of programmable self-assembling biological materials7-10, and on rapidly developing techniques for generating three-dimensional (3D) reconstructions from cryo-electron microscopy images of single particles, which provide high-resolution structural characterization of biological complexes11-13. Such single-particle 3D reconstruction approaches have not yet been successfully applied to the identification of synthetic inorganic nanomaterials with highly symmetrical cage-like shapes. Here, however, using a combination of cryo-electron microscopy and single-particle 3D reconstruction, we suggest the existence of isolated ultrasmall (less than 10 nm) silica cages ('silicages') with dodecahedral structure. We propose that such highly symmetrical, self-assembled cages form through the arrangement of primary silica clusters in aqueous solutions on the surface of oppositely charged surfactant micelles. This discovery paves the way for nanoscale cages made from silica and other inorganic materials to be used as building blocks for a wide range of advanced functional-materials applications.

Fluorescent Silica Nanoparticles with Well-Separated Intensity Distributions from Batch Reactions.

Silica chemistry provides pathways to uniquely tunable nanoparticle platforms for biological imaging. It has been a long-standing problem to synthesize fluorescent silica nanoparticles (SNPs) in batch reactions with high and low fluorescence intensity levels for reliable use as an intensity barcode, which would greatly increase the number of molecular species that could be tagged intracellularly and simultaneously observed in conventional fluorescence microscopy. Here, employing an amino-acid catalyzed growth, highly fluorescent SNP probes were synthesized with sizes <40 nm and well-separated intensity distributions, as mapped by single-particle imaging techniques. A seeded growth approach was used to minimize the rate of secondary particle formation. Organic fluorescent dye affinity for the SNP during shell growth was tuned using specifics of the organosilane linker chemistry. This work highlights design considerations in the development of fluorescent probes with well-separated intensity distributions synthesized in batch reactions for single-particle imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance.

Interface formation during silica encapsulation of colloidal CdSe/CdS quantum dots observed by in situ Raman spectroscopy.

We investigate the encapsulation of CdSe/CdS quantum dots (QDs) in a silica shell by in situ Raman spectroscopy and find a distinct shift of the CdS Raman signal during the first hours of the synthesis. This shift does not depend on the final silica shell thickness but on the properties of the initial core-shell QD. We find a correlation between the Raman shift rate and the speed of the silica formation and attribute this to the changing configuration of the outermost layers of the QD shell, where an interface to the newly formed silica is created. This dependence of Raman shift rate on the speed of silica formation process will give rise to many possible studies concerning the growth mechanism in the water-in-oil microemulsion, rendering in situ Raman a valuable instrument in monitoring this type of reaction.

Magnetic polaron on dangling-bond spins in CdSe colloidal nanocrystals.

Non-magnetic colloidal nanostructures can demonstrate magnetic properties typical for diluted magnetic semiconductors because the spins of dangling bonds at their surface can act as the localized spins of magnetic ions. Here we report the observation of dangling-bond magnetic polarons (DBMPs) in 2.8-nm diameter CdSe colloidal nanocrystals (NCs). The DBMP binding energy of 7 meV is measured from the spectral shift of the emission lines under selective laser excitation. The polaron formation at low temperatures occurs by optical orientation of the dangling-bond spins (DBSs) that result from dangling-bond-assisted radiative recombination of spin-forbidden dark excitons. Modelling of the temperature dependence of the DBMP-binding energy and emission intensity shows that the DBMP is composed of a dark exciton and about 60 DBSs. The exchange integral of one DBS with the electron confined in the NC is ∼0.12 meV.

On-Chip Integrated Quantum-Dot-Silicon-Nitride Microdisk Lasers.

Hybrid silicon nitride (SiN)-quantum-dot (QD) microlasers coupled to a passive SiN output waveguide with a 7 µm diameter and a record-low threshold density of 27 µJ cm-2 are demonstrated. A new design and processing scheme offers long-term stability and facilitates in-depth QD material and device characterization, thereby opening new paths for optical communication, sensing, and on-chip cavity quantum optics based on colloidal QDs.

Sensitive QD@SiO2-based immunoassay for triplex determination of cereal-borne mycotoxins.

A sensitive tool for simultaneous quantitative determination of three analytes in one single well of a microtiter plate is shown for the first time. The developed technique is based on use of colloidal quantum dot enrobed into a silica shell (QD@SiO2) derivatives as a highly responsive label. Silica-coated quantum dots were prepared and subsequently modified via the co-hydrolysis with tetraethylorthosilicate (TEOS) and various organosilane reagents. Different surface modification schemes were compared in terms of applicability of the obtained particles for the multiplex immunoassay, e.g. stability and simplicity of their conjugation with biomolecules. As model system a multiplex immunosorbent assay for screening of three mycotoxins (deoxynivalenol, zearalenone and aflatoxin B1) in cereal-based products was realized via a co-immobilization of three different specific antibodies (anti- deoxynivalenol, anti-zearalenone and anti-aflatoxin B1) in one single well of a microtiter plate. Mycotoxins were simultaneously determined by labelling their conjugates with QD@SiO2 emitting in different parts of the visible spectrum. The limits of detection for the simultaneous determination were 6.1 and 5.3, 5.4 and 4.1, and 2.6 and 1.9µgkg(-1) for deoxynivalenol, zearalenone and aflatoxin B1 in maize and wheat, respectively. As confirmatory method, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used.

Fabrication and characterization of on-chip silicon nitride microdisk integrated with colloidal quantum dots.

We designed and fabricated free-standing, waveguide-coupled silicon nitride microdisks hybridly integrated with embedded colloidal quantum dots. An efficient coupling of quantum dot emission to resonant disk modes and eventually to the access waveguides is demonstrated. The amount of light coupled out to the access waveguide can be tuned by controlling its dimensions and offset with the disk edge. These devices open up new opportunities for both on-chip silicon nitride integrated photonics and novel optoelectronic devices with quantum dots.

Synthesis, modification, bioconjugation of silica coated fluorescent quantum dots and their application for mycotoxin detection.

To create bright and stable fluorescent biolabels for immunoassay detection of mycotoxin deoxynivalenol in food and feed, CdSe/CdS/ZnS core-shell quantum dots (QDs) were encapsulated in silica nanoparticles through a water-in-oil reverse microemulsion process. The optical properties and stability of the obtained silica coated QDs (QD@SiO2), modified with amino, carboxyl and epoxy groups and stabilized with polyethylene glycol fragments, were characterized in order to assess their bioapplicability. The developed co-condensation techniques allowed maintaining 80% of the initial fluorescent properties and yielded stable fluorescent labels that could be easily activated and bioconjugated. Further, the modified QD@SiO2 were efficiently conjugated with antibodies and applied as a novel label in a microtiter plate based immunoassay and a quantitative column-based rapid immunotest for deoxynivalenol detection with IC50 of 473 and 20 ng/ml, respectively.

Nanoscale and Single-Dot Patterning of Colloidal Quantum Dots.

Using an optimized lift-off process we develop a technique for both nanoscale and single-dot patterning of colloidal quantum dot films, demonstrating feature sizes down to ~30 nm for uniform films and a yield of 40% for single-dot positioning, which is in good agreement with a newly developed theoretical model. While first of all presenting a unique tool for studying physics of single quantum dots, the process also provides a pathway toward practical quantum dot-based optoelectronic devices.