Luminescent CdS quantum dots as selective ion probes

Water-soluble luminescent CdS quantum dots (QDs) capped by polyphosphate, L-cysteine, and thioglycerol were synthesized in aqueous solution. The ligands were found to have a profound effect on the luminesence response of CdS QDs to physiologically important metal cations. Polyphosphate-capped CdS QDs were sensitive to nearly all mono- and divalent cations, showing no ion selectivity. Conversely, thioglycerol-capped CdS QDs were sensitive to only copper and iron ions. Similar concentrations of physiologically relevant cations, such as zinc, sodium, potassium, calcium, and magnesium ions did not affect the luminescence of thioglycerol-capped CdS QDs. On the other hand, L-cysteine-capped CdS QDs were sensitive to zinc ions and insensitive to other physiologically important cations, such as copper, calcium, and magnium ions. To demonstrate the detection capability of these new ion probes, L-cysteine and thioglycerol-capped CdS QDs were used to detect zinc and copper ions in physiological buffer samples. The detection limits were 0.8 microM for zinc (II) and 0.1 microM for copper (II) ions. The emission enhancement of the QDs by zinc (II) is attributed to activation of surface states, whereas the effective reduction of copper (II) to copper (I) may explain the emission decrease of the thioglycerol-capped CdS QDs when charged with copper ions. Unlike organic fluorescent dyes, the thioglycerol-capped luminescent CdS QDs discriminate between copper and zinc ions and are therefore suitable for the analysis of copper ions in biological samples in the presence of physiological concentrations of zinc ions. The interference of iron ions with zinc and copper ion detection is attributed to an inner filter effect, which is eliminated by adding fluoride ions to form the colorless complex FeF6(3-). To the best of our knowledge, this is first use of luminescent semiconductor quantum dots as selective ion probes in aqueous samples.     

Chemical Redox Modulation of the Surface Chemistry of CdTe Quantum Dots for Probing Ascorbic Acid in Biological Fluids

Most of the fluorescence resonance energy transfer (FRET)‐based sensors employing quantum dots (QDs) usually use organic fluorophores and gold nanoparticles as the quenchers. However, complex processes for the modification/immobilization of the QDs are always necessary, as the generation of FRET requires strict distance between the donor and acceptor. Herein, a simple chemical redox strategy for modulating the surface chemistry of the QDs to develop a QD‐based turn‐on fluorescent probe is reported. The principle of the strategy is demonstrated by employing CdTe QDs with KMnO₄ as the quencher and ascorbic acid as the target analyte. The fluorescence of CdTe QDs is quenched with a blue‐shift upon addition of KMnO₄ due to the oxidation of the Te atoms on the surface of the QDs. The quenched fluorescence of the QDs is then recovered upon addition of ascorbic acid due to the reduction of CdTeO₃/TeO₂ on the surface of the QDs to CdTe. The recovered fluorescence of the QDs increases linearly with the concentration of ascorbic acid from 0.3 to 10 µM . Thus, a novel QD‐based turn‐on fluorescent probe with a detection limit as low as 74 nM is developed for the sensitive and selective detection of ascorbic acid in biological fluids. The present approach avoids the complex modification/immobilization of the QDs involved in FRET‐based sensors, and opens a simple pathway to developing cost‐effective, sensitive, and selective QD‐based fluorescence turn‐on sensors/probes for biologically significant antioxidants.     

Anodic electrochemiluminescence of CdTe quantum dots and its energy transfer for detection of catechol derivatives

This work reported for the first time the anodic electrochemiluminescence (ECL) of CdTe quantum dots (QDs) in aqueous system and its analytical application based on the ECL energy transfer to analytes. The CdTe QDs were modified with mercaptopropionic acid to obtain water-soluble QDs and stable and intensive anodic ECL emission with a peak value at +1.17 V (vs Ag/AgCl) in pH 9.3 PBS at an indium tin oxide (ITO) electrode. The ECL emission was demonstrated to involve the participation of superoxide ion produced at the ITO surface, which could inject an electron into the 1Se quantum-confined orbital of CdTe to form QDs anions. The collision between these anions and the oxidation products of QDs led to the formation of the excited state of QDs and ECL emission. The ECL energy transfer from the excited CdTe QDs to quencher produced a novel methodology for detection of catechol derivatives. Using dopamine and L-adrenalin as model analytes, this ECL method showed wide linear ranges from 50 nM to 5 microM and 80 nM to 30 microM for these species. Both ascorbic acid and uric acid, which are common interferences, did not interfere with the detection of catechol derivatives in practical biological samples.     

Quantum dot/carrier-protein/haptens conjugate as a detection nanobioprobe for FRET-based immunoassay of small analytes with all-fiber microfluidic biosensing platform

This study demonstrates the use of carrier-protein/haptens conjugate (e.g., BSA/2,4-dichlorophenoxyacetic acid, 2,4-D-BSA) for biological modification of quantum dots (QDs) for the detection of small analytes. Bioconjugated QDs, which are used as a detection nanoimmunoprobe, were prepared through conjugating carboxyl QDs with 2,4-D-BSA conjugate. Based on the principle of quantum dot-fluorescence resonance energy transfer (QD-FRET), an all-fiber microfluidic biosensing platform has been developed for investigating FRET efficiency, immunoassay mechanism and format, and binding kinetics between QD immunoprobe and fluorescence labeled anti-2,4-D monoclonal antibody. The structure of multiplex-haptens/BSA conjugate coupling to QD greatly improves the FRET efficiency and the sensitivity of the nanosensor. With a competitive detection mode, samples containing different concentrations of 2,4-D were incubated with a given concentration of QD immunoprobe and fluorescence-labeled antibody, and then detected by the all-fiber microfluidic biosensing platform. A higher concentration of 2,4-D led to less fluorescence-labeled anti-2,4-D antibody bound to the QD immunoprobe surface and, thus, a lower fluorescence signal. The quantification of 2,4-D over concentration ranges from 0.5 nM to 3 μM with a detection limit determined as 0.5 nM. The performance of the nanosensor with spiked real water samples showed good recovery, precision, and accuracy, indicating that it was less suspectable to water matrix effects. With the use of different QD nanobioprobes modified by other carrier-protein/haptens conjugates, this biosensing protocol based on QD-FRET can be potentially applied for on-site, real-time, inexpensive, and easy-to-use monitoring of other trace analytes.     

Ultrasmall Near‐Infrared Non‐cadmium Quantum Dots for in vivo Tumor Imaging

The high tumor uptake of ultrasmall near‐infrared quantum dots (QDs) attributed to the enhanced permeability and retention effect is reported. InAs/InP/ZnSe QDs coated by mercaptopropionic acid (MPA) exhibit an emission wavelength of about 800 nm (QD800‐MPA) with very small hydrodynamic diameter (<10 nm). Using 22B and LS174T tumor xenograft models, in vivo and ex vivo imaging studies show that QD800‐MPA is highly accumulated in the tumor area, which is very promising for tumor detection in living mice. The ex vivo elemental analysis (Indium) using inductively coupled plasma (ICP) spectrometry confirm the tumor uptake of QDs. The ICP data are consistent with the in vivo and ex vivo fluorescence imaging. Human serum albumin (HSA)‐coated QD800‐MPA nanoparticles (QD800‐MPA‐HSA) show reduced localization in mononuclear phagocytic system‐related organs over QD800‐MPA plausibly due to the low uptake of QD800‐MPA‐HSA in macrophage cells. QD800‐MPA‐HSA may have great potential for in vivo fluorescence imaging.     

Ultrasensitive Pb2+ detection by glutathione-capped quantum dots

Water-soluble and stable quantum dots (QDs), CdTe and CdZnSe, are applied for ultrasensitive Pb(2+) detection. These QDs are capped with glutathione (GSH) shells. GSH and its polymeric form, phytochelatin, are employed by nature to detoxify heavy metal ions. As a result of specific interaction, the fluorescence intensity of GSH-capped QDs is selectively reduced in the presence of heavy metal ions such as Pb(2+). The detection limit of Pb(2+) is found to be 20 nM due to the superior fluorescence properties of QDs. Detailed studies by spectroscopy, microscopy, and dynamic light scattering show that competitive GSH binding of Pb(2+) with the QD core changed both the surface and photophysical properties of the QDs. Fluorescence of QDs is quenched, and QD aggregation occurs. Coupling the GSH-capped QDs with a high-throughput detection system, we have developed a simple scheme for quick and ultrasensitive Pb(2+) detection without the need for additional electronic devices. In the presence of ionic mixtures, our system is still capable of Pb(2+) detection with a detection limit as low as 40 nM. The system only becomes less sensitive when the ionic mixture is present at a very high concentration (i.e., > or =50 microM).     

On the quenching of semiconductor quantum dot photoluminescence by proximal gold nanoparticles

Luminescent quantum dots (QDs) were proven to be very effective fluorescence resonance energy transfer donors with an array of organic dye acceptors, and several fluorescence resonance energy transfer based biosensing assemblies utilizing QDs have been demonstrated in the past few years. Conversely, gold nanoparticles (Au-NPs) are known for their capacity to induce strong fluorescence quenching of conventional dye donors. Using a rigid variable-length polypeptide as a bifunctional biological linker, we monitor the photoluminescence quenching of CdSe-ZnS QDs by Au-NP acceptors arrayed around the QD surface, where the center-to-center separation distance was varied over a broad range of values (approximately 50-200 Angstrom). We measure the Au-NP-induced quenching rates for such QD conjugates using steady-state and time-resolved fluorescence measurements and examine the results within the context of theoretical treatments based on the F?rster dipole-dipole resonance energy transfer, dipole-metal particle energy transfer, and nanosurface energy transfer. Our results indicate that nonradiative quenching of the QD emission by proximal Au-NPs is due to long-distance dipole-metal interactions that extend significantly beyond the classical F?rster range, in agreement with previous studies using organic dye-Au-NP donor-acceptor pairs.     

A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future.     

Quantum Dot–Based FRET Immunoassay for HER2 Using Ultrasmall Affinity Proteins

Engineered scaffold affinity proteins are used in many biological applications with the aim of replacing natural antibodies. Although their very small sizes are beneficial for multivalent nanoparticle conjugation and efficient Förster resonance energy transfer (FRET), the application of engineered affinity proteins in such nanobiosensing formats has been largely neglected. Here, it is shown that very small (≈6.5 kDa) histidine‐tagged albumin‐binding domain‐derived affinity proteins (ADAPTs) can efficiently self‐assemble to zwitterionic ligand–coated quantum dots (QDs). These ADAPT–QD conjugates are significantly smaller than QD‐conjugates based on IgG, Fab', or single‐domain antibodies. Immediate applicability by the quantification of the human epidermal growth factor receptor 2 (HER2) in serum‐containing samples using time‐gated Tb‐to‐QD FRET detection on the clinical benchtop immunoassay analyzer KRYPTOR is demonstrated here. Limits of detection down to 40 × 10^?12m (≈8 ng mL^?1) are in a relevant clinical concentration range and outperform previously tested assays with antibodies, antibody fragments, and nanobodies.     

Ligand replacement-induced fluorescence switch of quantum dots for ultrasensitive detection of organophosphorothioate pesticides

The development of a simple and on-site assay for the detection of organophosphorus pesticed residues is very important for food safety and exosystem protection. This paper reports the surface coordination-originated fluorescence resonance energy transfer (FRET) of CdTe quantum dots (QDs) and a simple ligand-replacement turn-on mechanism for the highly sensitive and selective detection of organophosphorothioate pesticides. It has been demonstrated that coordination of dithizone at the surface of CdTe QDs in basic media can strongly quench the green emission of CdTe QDs by a FRET mechanism. Upon the addition of organophosphorothioate pesticides, the dithizone ligands at the CdTe QD surface are replaced by the hydrolyzate of the organophosphorothioate, and hence the fluorescence is turned on. The fluorescence turn on is immediate, and the limit of detection for chlorpyrifos is as low as ～0.1 nM. Two consecutive linear ranges allow a wide determination of chlorpyrifos concentrations from 0.1 nM to 10 μM. Importantly, the fluorescence turn-on chemosensor can directly detect chlorpyrifos residues in apples at a limit of 5.5 ppb, which is under the maximum residue limit allowed by the U.S. Environmental Protection Agency. The very simple strategy reported here should facilitate the development of fluorescence turn-on chemosensors for chemo/biodetection.     

Electrically Pumped White‐Light‐Emitting Diodes Based on Histidine‐Doped MoS2 Quantum Dots

MoS₂ quantum dots (QDs)‐based white‐light‐emitting diodes (QD‐WLEDs) are designed, fabricated, and demonstrated. The highly luminescent, histidine‐doped MoS₂ QDs synthesized by microwave induced fragmentation of 2D MoS₂ nanoflakes possess a wide distribution of available electronic states as inferred from the pronounced excitation‐wavelength‐dependent emission properties. Notably, the histidine‐doped MoS₂ QDs show a very strong emission intensity, which exceeds seven times of magnitude larger than that of pristine MoS₂ QDs. The strongly enhanced emission is mainly attributed to nitrogen acceptor bound excitons and passivation of defects by histidine‐doping, which can enhance the radiative recombination drastically. The enabled electroluminescence (EL) spectra of the QD‐WLEDs with the main peak around 500 nm are found to be consistent with the photoluminescence spectra of the histidine‐doped MoS₂ QDs. The enhanced intensity of EL spectra with the current increase shows the stability of histidine‐doped MoS₂ based QD‐WLEDs. The typical EL spectrum of the novel QD‐WLEDs has a Commission Internationale de l'Eclairage chromaticity coordinate of (0.30, 0.36) exhibiting an intrinsic broadband white‐light emission. The unprecedented and low‐toxicity QD‐WLEDs based on a single light‐emitting material can serve as an excellent alternative for using transition metal dichalcogenides QDs as next generation optoelectronic devices.     

Comparing intracellular stability and targeting of sulfobetaine quantum dots with other surface chemistries in live cells

The in vivo labeling of intracellular components with quantum dots (QDs) is very limited because of QD aggregation in the cell cytoplasm and/or QD confinement into lysosomal compartments. In order to improve intracellular targeting with QDs, various surface chemistries and delivery methods have been explored, but they have not yet been compared systematically with respect to the QD intracellular stability. In this work, the intracellular aggregation kinetics of QDs for three different surface chemistries based on ligand exchange or encapsulation with amphiphilic polymers are compared. For each surface chemistry, three delivery methods for bringing the nanoparticles into the cells are compared: electroporation, microinjection, and pinocytosis. It is concluded that the QD intracellular aggregation behavior is strongly dependent on the surface chemistry. QDs coated with dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands diffuse freely in cells for longer periods of time than for QDs in the other chemistries tested, and they can access all cytoplasmic compartments. Even when conjugated to streptavidin, these DHLA-SB QDs remain freely diffusing inside the cytoplasm and unaggregated, and they are able to reach a biotinylated target inside HeLa cells. Such labeling was more efficient when compared to commercial streptavidin-conjugated QDs, which may be due to the smaller size of DHLA-SB QDs and/or to their superior intracellular stability.     

Multiplex detection of protease activity with quantum dot nanosensors prepared by intein-mediated specific bioconjugation

We report here a protease sensing nanoplatform based on semiconductor nanocrystals or quantum dots (QDs) and bioluminescence resonance energy transfer (QD-BRET) to detect the protease activity in complex biological samples. These nanosensors consist of bioluminescent proteins as the BRET donor, quantum dots as the BRET acceptor, and protease substrates sandwiched between the two as a sensing group. An intein-mediated conjugation strategy was developed for site-specific conjugation of proteins to QDs in preparing these QD nanosensors. In this traceless ligation, the intein itself is spliced out and excluded from the final conjugation product. With this method, we have synthesized a series of QD nanosensors for highly sensitive detection of an important class of protease matrix metalloproteinase (MMP) activity. We demonstrated that these nanosensors can detect the MMP activity in buffers and in mouse serum with the sensitivity to a few nanograms per milliliter and secreted proteases by tumor cells. The suitability of these nanosensors for a multiplex protease assay has also been shown.     

Modulation of a photoswitchable dual-color quantum dot containing a photochromic FRET acceptor and an internal standard

Photoswitchable semiconductor nanoparticles, quantum dots (QDs), couple the advantages of conventional QDs with the ability to reversibly modulate the QD emission, thereby improving signal detection by rejection of background signals. Using a simple coating methodology with polymers incorporating a diheteroarylethene photochromic FRET acceptor as well as a spectrally distinct organic fluorophore, photoswitchable QDs were prepared that are small, biocompatible, and feature ratiometric dual emission. With programmed irradiation, the fluorescence intensity ratio can be modified by up to ～100%.     

Bright and efficient full-color colloidal quantum dot light-emitting diodes using an inverted device structure

We report highly bright and efficient inverted structure quantum dot (QD) based light-emitting diodes (QLEDs) by using solution-processed ZnO nanoparticles as the electron injection/transport layer and by optimizing energy levels with the organic hole transport layer. We have successfully demonstrated highly bright red, green, and blue QLEDs showing maximum luminances up to 23,040, 218,800, and 2250 cd/m(2), and external quantum efficiencies of 7.3, 5.8, and 1.7%, respectively. It is also noticeable that they showed turn-on voltages as low as the bandgap energy of each QD and long operational lifetime, mainly attributed to the direct exciton recombination within QDs through the inverted device structure. These results signify a remarkable progress in QLEDs and offer a practicable platform for the realization of QD-based full-color displays and lightings.     

Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip

There is a lack of reliable nanotoxicity assays available for monitoring and quantifying multiple cellular events in cultured cells. In this study, we used a microfluidic chip to systematically investigate the cytotoxicity of three kinds of well-characterized cadmium-containing quantum dots (QDs) with the same core but different shell structures, including CdTe core QDs, CdTe/CdS core–shell QDs, and CdTe/CdS/ZnS core-shell-shell QDs, in HEK293 cells. Using the microfluidic chip combined with fluorescence microscopy, multiple QD-induced cellular events including cell morphology, viability, proliferation, and QD uptake were simultaneously analysed. The three kinds of QDs showed significantly different cytotoxicities. The CdTe QDs, which are highly toxic to HEK293 cells, resulted in remarkable cellular and nuclear morphological changes, a dose-dependent decrease in cell viability, and strong inhibition of cell proliferation; the CdTe/CdS QDs were moderately toxic but did not significantly affect the proliferation of HEK293 cells; while the CdTe/CdS/ZnS QDs had no detectable influence on cytotoxicity with respect to cell morphology, viability, and proliferation. Our data indicated that QD cytotoxicity was closely related to their surface structures and specific physicochemical properties. This study also demonstrated that the microfluidic chip could serve as a powerful tool to systematically evaluate the cytotoxicity of nanoparticles in multiple cellular events.     

Suppression of radiative decay of CdTe quantum dots in a photonic crystal with a pseudogap

Abstract

Observation-angle dependence of the spontaneous emission life-time of CdTe quantum dots (QDs) embedded in a pseudogap photonic crystal (PC) film has been demonstrated. Comparison of two PC films with different photonic band-gaps (PBGs) differentiates the PBG effect from the electronic and/or chemical interactions between CdTe QDs and the host medium. This lifetime modification of QDs by a PC with pseudogap can be very useful in applications for optoelectronic devices such as QD lasers and QD switches.     

Polymer grafting from CdS quantum dots via AGET ATRP in miniemulsion

We report the synthesis of CdS quantum dot (QD)-poly(acrylate) nanocomposites using a recently developed catalytic system where activators are generated by electron transfer for atom-transfer radical polymerization (ATRP) in a miniemulsion. The QD surface was functionalized with a tris(alkyl)phosphine, previously modified with an ATRP chlorine initiator, and subsequent controlled polymerization was carried out from the functionalized surface of nanoparticles. The final material showed a high homogeneity and the QDs were evenly dispersed. The optical-absorption edge in the visible spectra of the nanocomposites attests the presence of the CdS QDs. Quantum confinement effects were assigned, though a blue shift in relation to the optical spectrum of the initial QDs has been observed.     

Lattice expansion in ZnSe quantum dots

Solid ZnSe quantum dots (QDs) have been prepared via chemical route. The QDs have been characterized by X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Photoluminescence (PL) and Ultraviolet-Visible Spectroscopy (Uv-Vis). The QD sizes were found to vary from 2.5 to 9.5 nm. The XRD measurement reveals an increase in the interplanar spacing in QDs as compared to their bulk counterpart. This observation is further supported by Rietveld analysis which establishes the formation of single phase zinc blende ZnSe QDs and confirms 3.9% lattice expansion. Calculations based upon the thermodynamical theory yield 8.7% concentration of vacancies due to the lattice expansion. We observe various peaks in the PL spectra which may arise either due to the QD size variations or the defects due to the vacancies.     

Application of Box–Behnken design in the optimization of a magnetic nanoparticle procedure for zinc determination in analytical samples by inductively coupled plasma optical emission spectrometry

This article describes the development of a procedure for zinc determination in water and biological samples after extraction by magnetic nanoparticles by inductively coupled plasma optical emission spectrometry (ICP-OES). The optimization strategy was carried out by using two level full factorial designs. Results of the two level full factorial design (2⁴) based on an analysis of variance demonstrated that only the pH, amount of extractant and amount of nanoparticles were statistically significant. Optimal conditions for three variables: pH of solution, amount of extractant (E), and amount of nanoparticles (N) for the extraction of zinc samples were obtained by using Box–Behnken design. These values were 3.8, 3.1 and 3.3 mg, for pH of solution, amount of nanoparticles and amount of extractant, respectively. Under the optimized experimental conditions, the detection limit of the proposed method followed by ICP-OES was found to be 0.8 μg L⁻¹. The method was applied to the determination of zinc in water and biological samples.