Interfacial Triboelectricity Lights Up Phosphor-Polymer Elastic Composites: Unraveling the Mechanism of Mechanoluminescence in Zinc Sulfide Microparticle-Embedded Polydimethylsiloxane Films.

Composites comprising copper-doped zinc sulfide phosphor microparticles embedded in polydimethylsiloxane (ZnS:Cu-PDMS) have received significant attention over the past decade because of their bright and durable mechanoluminescence (ML); however, the underlying mechanism of this unique ML remains unclear. This study reports empirical and theoretical findings that confirm this ML is an electroluminescence (EL) of the ZnS:Cu phosphor induced by the triboelectricity generated at the ZnS:Cu microparticle-PDMS matrix interface. ZnS:Cu microparticles that exhibit bright ML are coated with alumina, an oxide with strong positive triboelectric properties; the contact separation between this oxide coating and PDMS, a polymer with strong negative triboelectric properties, produces sufficient interfacial triboelectricity to induce EL in ZnS:Cu microparticles. The ML of ZnS:Cu-PDMS composites varies on changing the coating material, exhibiting an intensity that is proportional to the amount of interfacial triboelectricity generated in the system. Finally, based on these findings, a mechanism that explains the ML of phosphor-polymer elastic composites (interfacial triboelectric field-driven alternating-current EL model) is proposed in this study. It is believed that understanding this mechanism will enable the development of new materials (beyond ZnS:Cu-PDMS systems) with bright and durable ML.

Design and Synthesis of CdHgSe/HgS/CdZnS Core/Multi-Shell Quantum Dots Exhibiting High-Quantum-Yield Tissue-Penetrating Shortwave Infrared Luminescence.

Cdx Hg1- x Se/HgS/Cdy Zn1- y S core/multi-shell quantum dots (QDs) exhibiting bright tissue-penetrating shortwave infrared (SWIR; 1000-1700 nm) photoluminescence (PL) are engineered. The new structure consists of a quasi-type-II Cdx Hg1- x Se/HgS core/inner shell domain creating luminescent bandgap tunable across SWIR window and a wide-bandgap Cdy Zn1- y S outer shell boosting the PL quantum yield (QY). This compositional sequence also facilitates uniform and coherent shell growth by minimizing interfacial lattice mismatches, resulting in high QYs in both organic (40-80%) and aqueous (20-70%) solvents with maximum QYs of 87 and 73%, respectively, which are comparable to those of brightest visible-to-near infrared QDs. Moreover, they maintain bright PL in a photocurable resin (QY 40%, peak wavelength ≈ 1300 nm), enabling the fabrication of SWIR-luminescent composites of diverse morphology and concentration. These composites are used to localize controlled amounts of SWIR QDs inside artificial (Intralipid) and porcine tissues and quantitatively evaluate the applicability as luminescent probes for deep-tissue imaging.

Inorganic-Ligand Quantum Dots Meet Inorganic-Ligand Semiconductor Nanoplatelets: A Promising Fusion to Construct All-Inorganic Assembly.

By the reaction of inorganic-ligand CdS/Cd2+ quantum dots (QDs) with inorganic-ligand CdSe/CdS/S2- nanoplatelets (NPLs), semiconductor CdS QDs were fused with CdSe/CdS NPLs to yield all-inorganic assemblies, accompanied by great photoluminescence-enhancement. These all-inorganic assemblies facilitate charge transport between each other and open up interesting prospects with electronic and optoelectronic nanodevices.

An Automated Microfluidic Assay for Photonic Crystal Enhanced Detection and Analysis of an Antiviral Antibody Cancer Biomarker in Serum.

We report on the implementation of an automated platform for detecting the presence of an antibody biomarker for human papillomavirus-associated oropharyngeal cancer from a single droplet of serum, in which a nanostructured photonic crystal surface is used to amplify the output of a fluorescence-linked immunosorbent assay. The platform is comprised of a microfluidic cartridge with integrated photonic crystal chips that interfaces with an assay instrument that automates the introduction of reagents, wash steps, and surface drying. Upon assay completion, the cartridge interfaces with a custom laser-scanning instrument that couples light into the photonic crystal at the optimal resonance condition for fluorescence enhancement. The instrument is used to measure the fluorescence intensity values of microarray spots corresponding to the biomarkers of interest, in addition to several experimental controls that verify correct functioning of the assay protocol. In this work, we report both dose-response characterization of the system using anti-E7 antibody introduced at known concentrations into serum and characterization of a set of clinical samples from which results were compared with a conventional enzyme-linked immunosorbent assay (ELISA) performed in microplate format. The demonstrated capability represents a simple, rapid, automated, and high-sensitivity method for multiplexed detection of protein biomarkers from a low-volume test sample.

Measuring and Predicting the Internal Structure of Semiconductor Nanocrystals through Raman Spectroscopy.

Nanocrystals composed of mixed chemical domains have diverse properties that are driving their integration in next-generation electronics, light sources, and biosensors. However, the precise spatial distribution of elements within these particles is difficult to measure and control, yet profoundly impacts their quality and performance. Here we synthesized a unique series of 42 different quantum dot nanocrystals, composed of two chemical domains (CdS:CdSe), arranged in 7 alloy and (core)shell structural classes. Chemometric analyses of far-field Raman spectra accurately classified their internal structures from their vibrational signatures. These classifications provide direct insight into the elemental arrangement of the alloy as well as an independent prediction of fluorescence quantum yield. This nondestructive, rapid approach can be broadly applied to greatly enhance our capacity to measure, predict and monitor multicomponent nanomaterials for precise tuning of their structures and properties.

Lipoprotein Nanoplatelets: Brightly Fluorescent, Zwitterionic Probes with Rapid Cellular Entry.

Semiconductor nanoplatelets (NPLs) are planar nanocrystals that have recently attracted considerable attention due to their quantum-well-like physics, atomically precise thickness, and unique photophysical properties such as narrow-band fluorescence emission. These attributes are of potential interest for applications in biomolecular and cellular imaging, but it has been challenging to colloidally stabilize these nanocrystals in biological media due to their large dimensions and tendency to aggregate. Here we introduce a new colloidal material that is a hybrid between a NPL and an organic nanodisc composed of phospholipids and lipoproteins. The phospholipids adsorb to flat surfaces on the NPL, and lipoproteins bind to sharp edges to enable monodisperse NPL encapsulation with long-term stability in biological buffers and high-salt solutions. The lipoprotein NPLs (L-NPLs) are highly fluorescent, with brightness comparable to that of wavelength-matched quantum dots at both the ensemble and single-molecule levels. They also exhibit a unique feature of rapid internalization into living cells, after which they retain their fluorescence. These unique properties suggest that L-NPLs are particularly well suited for applications in live-cell single-molecule imaging and multiplexed cellular labeling.

Multidentate Polymer Coatings for Compact and Homogeneous Quantum Dots with Efficient Bioconjugation.

Quantum dots are fluorescent nanoparticles used to detect and image proteins and nucleic acids. Compared with organic dyes and fluorescent proteins, these nanocrystals have enhanced brightness, photostability, and wavelength tunability, but their larger size limits their use. Recently, multidentate polymer coatings have yielded stable quantum dots with small hydrodynamic dimensions (≤10 nm) due to high-affinity, compact wrapping around the nanocrystal. However, this coating technology has not been widely adopted because the resulting particles are frequently heterogeneous and clustered, and conjugation to biological molecules is difficult to control. In this article we develop new polymeric ligands and optimize coating and bioconjugation methodologies for core/shell CdSe/Cd(x)Zn(1-x)S quantum dots to generate homogeneous and compact products. We demonstrate that "ligand stripping" to rapidly displace nonpolar ligands with hydroxide ions allows homogeneous assembly with multidentate polymers at high temperature. The resulting aqueous nanocrystals are 7-12 nm in hydrodynamic diameter, have quantum yields similar to those in organic solvents, and strongly resist nonspecific interactions due to short oligoethylene glycol surfaces. Compared with a host of other methods, this technique is superior for eliminating small aggregates identified through chromatographic and single-molecule analysis. We also demonstrate high-efficiency bioconjugation through azide-alkyne click chemistry and self-assembly with hexa-histidine-tagged proteins that eliminate the need for product purification. The conjugates retain specificity of the attached biomolecules and are exceptional probes for immunofluorescence and single-molecule dynamic imaging. These results are expected to enable broad utilization of compact, biofunctional quantum dots for studying crowded macromolecular environments such as the neuronal synapse and cellular cytoplasm.

Quantum Dot Surface Engineering: Toward Inert Fluorophores with Compact Size and Bright, Stable Emission.

The surfaces of colloidal nanocrystals are complex interfaces between solid crystals, coordinating ligands, and liquid solutions. For fluorescent quantum dots, the properties of the surface vastly influence the efficiency of light emission, stability, and physical interactions, and thus determine their sensitivity and specificity when they are used to detect and image biological molecules. But after more than 30 years of study, the surfaces of quantum dots remain poorly understood and continue to be an important subject of both experimental and theoretical research. In this article, we review the physics and chemistry of quantum dot surfaces and describe approaches to engineer optimal fluorescent probes for applications in biomolecular imaging and sensing. We describe the structure and electronic properties of crystalline facets, the chemistry of ligand coordination, and the impact of ligands on optical properties. We further describe recent advances in compact coatings that have significantly improved their properties by providing small hydrodynamic size, high stability and fluorescence efficiency, and minimal nonspecific interactions with cells and biological molecules. While major progress has been made in both basic and applied research, many questions remain in the chemistry and physics of quantum dot surfaces that have hindered key breakthroughs to fully optimize their properties.

Small quantum dots conjugated to nanobodies as immunofluorescence probes for nanometric microscopy.

Immunofluorescence, a powerful technique to detect specific targets using fluorescently labeled antibodies, has been widely used in both scientific research and clinical diagnostics. The probes should be made with small antibodies and high brightness. We conjugated GFP binding protein (GBP) nanobodies, small single-chain antibodies from llamas, with new ∼7 nm quantum dots. These provide simple and versatile immunofluorescence nanoprobes with nanometer accuracy and resolution. Using the new probes we tracked the walking of individual kinesin motors and measured their 8 nm step sizes; we tracked Piezo1 channels, which are eukaryotic mechanosensitive channels; we also tracked AMPA receptors on living neurons. Finally, we used a new super-resolution algorithm based on blinking of (small) quantum dots that allowed ∼2 nm precision.

Stable small quantum dots for synaptic receptor tracking on live neurons.

We developed a coating method to produce functionalized small quantum dots (sQDs), about 9 nm in diameter, that were stable for over a month. We made sQDs in four emission wavelengths, from 527 to 655 nm and with different functional groups. AMPA receptors on live neurons were labeled with sQDs and postsynaptic density proteins were visualized with super-resolution microscopy. Their diffusion behavior indicates that sQDs access the synaptic clefts significantly more often than commercial QDs.

Magnetically Controlled Intraocular Delivery of Dexamethasone Using Silica-Coated Magnetic Nanoparticles.

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina.

Surface-dependent, ligand-mediated photochemical etching of CdSe nanoplatelets.

Photochemical etching of CdSe nanoplatelets was studied to establish a relationship between the nanocrystal surface and the photochemical activity of an exciton. Nanoplatelets were synthesized in a mixture of octylamine and oleylamine for the wurtzite (W) lattice or in octadecene containing oleic acid for the zinc-blende (ZB) lattice. For photochemical etching, nanoplatelets were dispersed in chloroform containing oleylamine and tributylphosphine in the absence or presence of oleic acid and then irradiated with light at the band-edge absorption maxima. Etching phenomena were characterized using UV-vis absorption spectroscopy and transmission electron microscopy. The absorption spectra of both W and ZB CdSe nanoplatelets showed that the exciton was confined in one dimension along the thickness. However, the two nanoplatelets presented different etching kinetics and erosion patterns. The rate of etching for W CdSe nanoplatelets was much faster than that for ZB nanoplatelets. Small holes were uniformly perforated on the planar surface of W nanoplatelets, whereas the corners and edges of ZB nanoplatelets were massively eroded without a significant perforation on the planar surface. This suggests that the amine-passivated surface of trivalent cadmium atoms on CdSe nanoplatelets is photochemically active, but the carboxylate-passivated surface of divalent cadmium atoms is not. Hence, the ligand, which induces the growth of W or ZB CdSe nanoplatelets, mediates the surface-dependent photochemical etching. This result implies that an electron-hole pair can be extracted from the planar surface of amine-passivated W nanoplatelets but from the corners and edges of carboxylate-passivated ZB nanoplatelets.

Antibody Self-Assembly Maximizes Cytoplasmic Immunostaining Accuracy of Compact Quantum Dots.

Antibody conjugates of quantum dots (QDs) are expected to transform immunofluorescence staining by expanding multiplexed analysis and improving target quantification. Recently, a new generation of small QDs coated with multidentate polymers has improved QD labeling density in diverse biospecimens, but new challenges prevent their routine use. In particular, these QDs exhibit nonspecific binding to fixed cell nuclei and their antibody conjugates have random attachment orientations. This report describes four high-efficiency chemical approaches to conjugate antibodies to compact QDs. Methods include click chemistry and self-assembly through polyhistidine coordination, both with and without adaptor proteins that directionally orient antibodies. Specific and nonspecific labeling are independently analyzed after application of diverse blocking agent classes, and a new assay is developed to quantitatively measure intracellular labeling density based on microtubule stain connectivity. Results show that protein conjugation to the QD surface is required to simultaneously eliminate nonspecific binding and maintain antigen specificity. Of the four conjugation schemes, polyhistidine-based coordination of adaptor proteins with antibody self-assembly yields the highest intracellular staining density and the simplest conjugation procedure. Therefore, antibody and adaptor protein orientation, in addition to blocking optimization, are important determinants of labeling outcomes, insights that can inform translational development of these more compact nanomaterials.

Shell and ligand-dependent blinking of CdSe-based core/shell nanocrystals.

Blinking of zinc blende CdSe-based core/shell nanocrystals is studied as a function of shell materials and surface ligands. CdSe/ZnS, CdSe/ZnSe/ZnS and CdSe/CdS/ZnS core/shell nanocrystals are prepared by colloidal synthesis and six monolayers of larger bandgap shell materials are grown over the CdSe core. Organic-soluble nanocrystals covered with stearate are made water-soluble by ligand exchange with 3-mercaptopropionic acid. The light-emitting states of nanocrystals are characterized by absorption and emission spectroscopy as well as photoluminescence lifetime measurements in solution. The blinking time trace is recorded for single nanocrystals on a glass coverslip. Both on- and off-time distributions are fitted to the power law. The power-law exponents vary, depending on shell materials and surface ligands. The off-time exponents for organic and water-soluble nanocrystals are measured in the range of 1.36-1.55 and 1.25-1.37, respectively, while their on-time exponents are spread in the range of 1.53-1.86 and 1.85-2.17, respectively. Water-soluble surface passivation with thiolate prolongs the dark period regardless of shell materials and core/shell structures. Of the core/shell structures, CdSe/CdS/ZnS exhibits the longest bright state. The on/off-time exponents are inversely correlated, although the successive on/off events are not individually correlated. A two competing charge-tunneling model is presented to describe the variation of on- and off-time exponents with shell materials and surface ligands.

Compact Quantum Dots for Quantitative Cytology.

In this chapter, we describe the preparation of fluorescent quantum dots for imaging and measuring protein expression in cells. Quantum dots are nanocrystals that have numerous advantages for biomolecular detection compared with organic dyes and fluorescent proteins, but their large size has been a limiting factor. We describe the synthesis of nanoparticles smaller than 10 nm (smaller than an antibody), their attachment to monoclonal antibodies through click chemistry, characterization of the conjugates, and use for labeling of cellular antigens. We further discuss the unique advantages and challenges associated with this approach compared with conventional immunofluorescence techniques.

Comparison of signal detection of tumour necrosis factor-α inhibitors using the Korea Adverse Events Reporting System Database, 2005-2016.

OBJECTIVES: There are no pharmacovigilance studies on adverse event (AE) data for tumour necrosis factor alpha (TNFα) inhibitors in South Korea. We analysed AEs induced by adalimumab, infliximab, and etanercept METHODS: We used data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Events Reporting System Database (KIDS-KD) collected between 2005 and 2016. We used three different signal detection methods: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The drug was compared with drug labels in the USA and Korea. Logistic regression analysis identified AEs that are more likely to occur with drug use. RESULTS: Of the 5594 AEs identified, 350, 452, and 71 were related to adalimumab, infliximab, and etanercept, respectively. We identified seven new signals, which were not listed on drug labels in either Korea or the USA, for AEs associated with the study drugs: two for adalimumab (medication error and drug failure), two for infliximab (palpitation and temperature sensation change), and three for etanercept (hyperkeratosis, acne, and thyroid neoplasm malignant). Injection site pain (OR 6.14, 95% CI 1.15-32.74) and alopecia (OR 4.54, 95% CI 1.16-17.77) for adalimumab, chest pain (OR 6.01, 95% CI 1.35-26.77) for infliximab, and uveitis (OR 10.11, 95% CI 1.13-90.77) for etanercept were more likely to be reported in patients with each TNFα inhibitor than in those without, respectively. CONCLUSIONS: Seven new signals that were not included in the current label were identified for TNFα inhibitors and should be updated and monitored.Key Points• Large-scale spontaneous AE reporting data and data mining techniques are useful for detecting signals of rare AEs as well as common AEs induced by drugs.• Drug labels should be updated to reflect signals that are newly discovered by continuous monitoring.

Hospital Nurses' Perception of Death and Self-Reported Performance of End-of-Life Care: Mediating Role of Attitude towards End-of-Life Care.

Few studies have explored how nurses in acute care hospitals perceive and perform end-of-life care in Korea. Therefore, this study aimed to evaluate the influence of nurses' perceptions of death on end-of-life care performance and analyze the mediating role of attitude towards end-of-life care among hospital nurses. This cross-sectional study included a total of 250 nurses who have had experience with end-of-life care from four general hospitals in Korea. We used the Korean validated tools with the View of Life and Death Scale, the Frommelt Attitudes Toward Care of the Dying (FATCOD) scale, and the performance of end-of-life care. Hierarchical linear regression and mediation analysis, applying the bootstrapping method. The results of hierarchical linear regression showed that nurses' positive perceptions of death and attitude towards end-of-life care were significantly associated with their performance of end-of-life care. A mediation analysis further revealed that nurses' attitude towards end-of-life care mediates the relationship between the perceptions of death and performance of end-of-life care. Our findings suggest that supportive and practical death educational programs should be designed, based on nurses' professional experience and work environment, which will enable them to provide better end-of-life care.

Collision-induced dissociation of II-VI semiconductor nanocrystal precursors, Cd2+ and Zn2+ complexes with trioctylphosphine oxide, sulfide, and selenide.

The metal (M = Cd2+ and Zn2+) complexes with trioctylphosphine chalcogenide (TOPE, E = O, S, and Se) are prepared by electrospray ionization, and their relative stabilities and intramolecular reactions are studied by collision-induced dissociation (CID) with Xe under single collision conditions. These metal-TOPE complexes are considered as molecular precursors for the colloidal synthesis of II-VI compound semiconductor nanocrystals employing TOPO as a metal-coordinating solvent and TOPS or TOPSe as a chalcogen precursor. Of the various [M + nTOPE]2+ (n = 2-7) ions generated by ESI, the n = 2-4 complexes are characterized by CID as a function of collision energy. The collision energy at 50% dissociation (E50%) is determined from the cracking curve and the relative stabilities of the complexes are established. Between the two metal ions, the zinc-TOPE complexes are more stable than the cadmium-TOPE complexes when n = 2-3, whereas their stabilities are reversed when n = 4. Of the TOPE, TOPO binds most strongly to the metal ion, while TOPSe does most weakly. Upon CID, loss of TOPE occurs exclusively from the tetra-TOPE complexes, while extensive fragmentation of TOPE takes place from the di-TOPE complexes, showing the signature of the metal chacogenide formation. The nucleation of nanocrystals appears to begin with cracking of [M + 2TOPE]2+ (E = S and Se).

Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions.

The distribution of single-cell properties across a population of cells can be measured using diverse tools, but no technology directly quantifies the biochemical stimulation events regulating these properties. Here we report digital counting of growth factors in single cells using fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy (QDC-3DM) to reveal physiologically relevant cell stimulation distributions. We calibrate the fluorescence intensities of individual compact quantum dots labeled with epidermal growth factor (EGF) and demonstrate the necessity of near-infrared emission to overcome intrinsic cellular autofluoresence at the single-molecule level. When applied to human triple-negative breast cancer cells, we observe proportionality between stimulation and both receptor internalization and inhibitor response, reflecting stimulation heterogeneity contributions to intrinsic variability. We anticipate that QDC-3DM can be applied to analyze any peptidic ligand to reveal single-cell correlations between external stimulation and phenotypic variability, cell fate, and drug response.

Water-resistant AgBiS2 colloidal nanocrystal solids for eco-friendly thin film photovoltaics.

Lead-free, water-resistant photovoltaic absorbers are of significant interest for use in environment-friendly and water-stable thin film solar cells. However, there are no reports on the water-resistance characteristics of such photoactive materials. Here, we demonstrate that silver bismuth sulfide (AgBiS2) nanocrystal solids exhibit inherent water resistance and can be employed as effective photovoltaic absorbers in all-solid-state thin film solar cells that show outstanding air and moisture stabilities under ambient conditions. The results of X-ray photon spectroscopy (XPS) and X-ray diffraction (XRD) analyses show that there is no change in the chemical composition and crystal structure of the AgBiS2 nanocrystal solids after a water treatment. Based on these results, AgBiS2 nanocrystal solar cells are fabricated. These devices also do not show any drop in performance after a water treatment, confirming that the AgBiS2 nanocrystal solids are indeed highly water-resistant. In contrast, lead sulfide (PbS) colloidal quantum dot (CQD) solar cells show significant decrease in performance after a similar water treatment. Using XPS analysis and density functional theory (DFT) calculations, we confirm that the iodine removal and the surface hydroxylation of the water-treated PbS CQD solids are the primary reasons for the observed decrease in the device performance of the CQD solar cells.