Visualizing vitreous using quantum dots as imaging agents

Vitreous is transparent tissue located between the lens and the retina of the eye, thus, difficult to look at by even ophthalmological microscope. But vitreous is connected with some sight-threatening eye diseases, for example, retinal detachment, macular hole, epi-retinal membrane, and so forth. Quantum dots (QDs) have been applied to a wide range of biological studies by taking advantage of their fluorescence properties. We established a novel technique of aqueous colloidal QD (ACQD) as a vitreous lesion detector. When compared with some conventional dyes used for clinical situation, i.e. fluorescein, indocyanine green, and triamcinolone acetonide, ACQD exerted a higher performance to detect a Weiss Ring. Furthermore ACQD is also effective to perform vitrectomy, an eye surgery to cut and eliminate vitreous. Some functional structures in vitreous are detected clearly when ACQD was injected into an enucleated porcine eye. We demonstrated that ACQD enabled any ophthalmic surgeon to perform vitrectomy reliably, easily, and more safely. Taken together, the ACQD-oriented vitreous staining system will promote ophthalmological science, and it will raise the cure rate of eye diseases     

Superlocalization spectral imaging microscopy of a multicolor quantum dot complex

The key factor of realizing super-resolution optical microscopy at the single-molecule level is to separately position two adjacent molecules. An opportunity to independently localize target molecules is provided by the intermittency (blinking) in fluorescence of a quantum dot (QD) under the condition that the blinking of each emitter can be recorded and identified. Herein we develop a spectral imaging based color nanoscopy which is capable of determining which QD is blinking in the multicolor QD complex through tracking the first-order spectrum, and thus, the distance at tens of nanometers between two QDs is measured. Three complementary oligonucleotides with lengths of 15, 30, and 45 bp are constructed as calibration rulers. QD585 and QD655 are each linked at one end. The measured average distances are in good agreement with the calculated lengths with a precision of 6 nm, and the intracellular dual-color QDs within a diffraction-limited spot are distinguished.     

Aqueous CdPbS quantum dots for near-infrared imaging

Quantum dots (QDs) are semiconducting nanocrystals that have photoluminescent (PL) properties brighter than fluorescent molecules and do not photo-bleach, ideal for in vivo imaging of diseased tissues or monitoring of biological processes. Near-infrared (NIR) fluorescent light within the window of 700-1000 nm, which is separated from the major absorption peaks of hemoglobin and water, has the potential to be detected several millimeters under the surface with minimal interference from tissue autofluorescence. Here we report the synthesis and bioimaging demonstration of a new NIR QDs system, namely, CdPbS, made by an aqueous approach with 3-mercaptopropionic acid (MPA) as the capping molecule. The aqueous-synthesized, MPA-capped CdPbS QDs exhibited an NIR emission in the range of 800-950 nm with x(i) ≥ 0.3, where x(i) denotes the initial Pb molar fraction during the synthesis. Optimal PL performance of the CdPbS QDs occurred at x(i) = 0.7, which was about 4 nm in size as determined by transmission electron microscopy, had a rock salt structure and a quantum yield of 12%. Imaging of CdPbS QDs was tested in membrane staining and transfection studies. Cells transfected with CdPbS QDs were shown to be visible underneath a slab of chicken muscle tissue of up to 0.7 mm in thickness without the use of multiple-photon microscopy.     

Semiconductor quantum dots for in vivo imaging

Quantum dots play an important role in the in vitro, ex vivo, and in vivo optical imaging. Dramatic improvements have been achieved in the aspect of surface modification, biocompatibility, and targeting specificity, which had significant impact on the in vivo applications of quantum dots. This review summarizes the recent advances of quantum dots for in vivo imaging using both non-specific and targeted approaches. The toxicity of cadmium chalcogenide materials and alternative approaches such as the use of doped nanocrystal quantum dots were also discussed. The integration of quantum dots with other imaging techniques is also expected to give rise to a new generation of multifunctional probes for biomedical applications.     

Designed biointerface using near-infrared quantum dots for ultrasensitive surface plasmon resonance imaging biosensors

The surface plasmon resonance imaging chip biointerface is fully designed using near-infrared (NIR) quantum dots (QDs) for the enhancement of surface plasmon resonance imaging (SPRi) signals in order to extend their application for medical diagnostics. The measured SPRi detection signal following the QD binding to the surface was amplified 25-fold for a 1 nM concentration of single-stranded DNA (ssDNA) and 50-fold for a 1 μg/mL concentration of prostate-specific antigen (PSA), a cancer biomarker, thus substantiating their wide potential to study interactions of a diverse set of small biomolecules. This significant enhancement is attributed to the QD's mass-loading effect and spontaneous emission coupling with propagating surface plasmons, which allowed the SPRi limit of detection to be reduced to 100 fM and 100 pg/mL for ssDNA and PSA, respectively. Furthermore, this study illustrates the potential of SPRi to be easily integrated with fluorescent imaging for advanced correlative surface-interaction analysis.     

Scanned probe imaging of quantum dots inside InAs nanowires

We show how a scanning probe microscope (SPM) can be used to image electron flow through InAs nanowires, elucidating the physics of nanowire devices on a local scale. A charged SPM tip is used as a movable gate. Images of nanowire conductance versus tip position spatially map the conductance of InAs nanowires at liquid-He temperatures. Plots of conductance versus backgate voltage without the tip present show complex patterns of Coulomb-blockade peaks. Images of nanowire conductance identify their source as multiple quantum dots formed by disorder along the nanowire--each dot is surrounded by a series of concentric rings corresponding to Coulomb blockade peaks. An SPM image locates the dots and provides information about their size. In this way, SPM images can be used to understand the features that control transport through nanowires. The nanowires were grown from metal catalyst particles and have diameters approximately 80 nm and lengths 2-3 microm.     

Achieving stem cell imaging and osteogenic differentiation by using nitrogen doped graphene quantum dots

Nitrogen doped graphene quantum dots (N-GQDs) were synthesized to explore and extend their potential applications in biomedical field. The hemocompatibility and cytotoxity of the obtained N-GQDs were primarily assessed at concentrations ranging from 10 to 100?μg/ml. From the results, it was found that the proliferation of rat Bone Mesenchymal Stem Cells (rBMSCs) was depressed to a certain extent after incubating with the high concentration (100?μg/ml) of N-GQDs. The nanoscale size and superior dispersibility endow N-GQDs with good cell permeability. Meanwhile, owing to their intrinsic photoluminescence characteristic, the N-GQDs can be used to label cells with high uniformity and light stability in absence of chemical dyes. More importantly, the up-regulated expression of alkaline phosphate (ALP), extracellular matrix, osteopontin (OPN) and osteocalcin (OCN) in rBMSCs cultured with N-GQDs, indicating N-GQDs have the abilities to promote rBMSCs osteogenic differentiation. This work would help give a new insight into the advantages of N-GQDs and pave the way for application of N-GQDs in regenerative medicine fields.

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Photoluminescence enhancement of quantum dots with different emission wavelengths using oxide shell-isolated Au nanoparticles

Journal of Materials Science - Improving the quantum yield of non-toxic InP/ZnS QDs is essential for its commercial application in illumination and displays. In this work, single size Au...     

Bioconjugated quantum dots as fluorescent probes for biomedical imaging

Luminescent semiconductor quantum dots have become an important class of fluorescent labels for biological and biomedical imaging. In comparison with conventional organic dyes and fluorescent proteins, quantum dots have extraordinary fluorescent properties including high brightness, high resistance to photobleaching and tunable wavelengths. In this review, we briefly discuss the properties and modification of quantum dots. We focus on the applications of quantum dots in biomedical imaging, including molecular detection, live cell imaging and in vivo imaging. The toxicity of the quantum dots to cells and animals is also discussed.     

Transfection of aqueous CdS quantum dots using polyethylenimine

In this study, we have examined the transfection of aqueous CdS quantum dots (QDs) in the cytoplasm of PC12 neuronal cells using polyethylenimine (PEI) as carrier. The CdS QDs were prepared using a unique aqueous synthesis method, at 5?nm in size and capped with 3-mercaptopropyltrimethoxysilane (MPS). They exhibited a quantum yield of 7.5% and a zeta potential of -25?mV. With PEI they formed complexes by electrostatic attraction. At PEI/QD number ratios of>100, the PEI-QD complexes obtained exhibited a saturated size of about 24?nm and a zeta potential of about 15?mV. Confocal microscopy showed that PEI-QD complexes of a PEI/QD number ratio of 200 were successfully internalized and uniformly distributed inside the cells, indicating that the PEI-QD complexes were able to rupture the vesicles to enter the cytoplasm without aggregation. In addition, we showed that the presence of the PEI did not reduce the photoluminescence of the QDs and only mildly reduced the mitochondrial activity of the transfected cells-with no apparent reduction at a PEI/QD ratio of <40 to about 30% reduction at a PEI/QD number ratio of 200.     

Separation of bioconjugated quantum dots using capillary electrophoresis

Capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection was used to separate different bioconjugated CdSe/ZnS quantum dots (QDs). The QD nanocrystals studied were conjugated to the biomolecules streptavidin, biotin, and immunoglobulin G. The bioconjugated QDs showed different electrophoretic mobilities, which appear to depend upon the biomolecule that is attached to the QD and the buffer solution used. The use of a polymeric additive into the CE run buffer improved the resolution of the bioconjugates. Under CE conditions, the interaction between QD bioconjugates containing streptavidin (QDSt) and biotin (QDBi) was monitored. Under a given set of experimental conditions, the fluorescence intensity of QDSt and QDBi emitting light at 655 nm indicated that about 90% of QDBi complexed with 70% of QDSt. A two-color experiment that made use of two different sizes of QD (i.e., 585 and 655 nm) indicated that 30% of the 655 nm QDBi complexed with 53% of the 585 nm QDSt. The use of QDs with different emission properties allows the selective monitoring of two different wavelengths while using one single excitation source. This, in turn, allowed the monitoring of overlapping peaks in the electropherogram when newly formed products resulting from the interaction of the two bioconjugated QDs appeared.     

Photoluminescence imaging of focused ion beam induced individual quantum dots

We report on scanning microphotoluminescence measurements that spectrally and spatially resolve emission from individual InAs quantum dots that were induced by focused ion beam patterning. Multilayers of quantum dots were spaced 2 μm apart, with a minimum single dot emission line width of 160 μeV, indicating good optical quality for dots patterned using this technique. Mapping 16 array sites, at least 65% were occupied by optically active dots and the spectral inhomogeneity was within 30 meV.     

Arginine-glycine-aspartic acid-conjugated dendrimer-modified quantum dots for targeting and imaging melanoma

Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. Quantum dots have been broadly investigated for their potential application in cancer molecular imaging. In present work, CdSe quantum dots were synthesized, polyamidoamine dendrimers were used to modify surface of quantum dots and improve their solubility in water solution. Then, dendrimer-modified CdSe quantum dots were conjugated with arginine-glycine-aspartic acid (RGD) peptides. These prepared nanoprobes were injected into nude mice loaded with melanoma (A375) tumor xenografts via tail vessels, IVIS imaging system was used to image the targeting and bio-distribution of as-prepared nanoprobes. The dendrimer-modified quantum dots exhibit water-soluble, high quantum yield, and good biocompatibility. RGD-conjugated quantum dots can specifically target human umbilical vein endothelial cells (HUVEC) and A375 melanoma cells, as well as nude mice loaded with A735 melanoma cells. High-performance RGD-conjugated dendrimers modified quantum dot-based nanoprobes have great potential in application such as tumor diagnosis and therapy.     

Aptamer-conjugated dendrimer-modified quantum dots for cancer cell targeting and imaging

Targeted quantum dots have shown potential as a platform for development of cancer imaging. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In the present work, polyamidoamine dendrimers were used to modify quantum dots and improve their solubility in water solution. Then, dendrimer-modified quantum dot nanocomposites conjugated with a DNA aptamer, GBI-10, can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. Aptamer-conjugated quantum dots can specifically target U251 human glioblastoma cells. High-performance aptamer-conjugated dendrimer-modified quantum dots maybe general nanoprobes, and have great potential in applications such as cancer targeting and molecular imaging.     

Photoluminescent two-dimensional SiC quantum dots for cellular imaging and transport

Two-dimensional (2D) ultrathin SiC has received intense attention due to its broad band gap and resistance to large mechanical deformation and external chemical corrosion. However, the synthesis and application of ultrasmall 2D SiC quantum dots (QDs) has not been explored. Herein, we synthesize a type of monolayered 2D SiC QDs with advanced photoluminescence (PL) properties via a facile hydrothermal route. Their average size and thickness can be easily adjusted by altering the reaction time. The ultrasmall 2D SiC QDs exhibit a long fluorescence lifetime of 2.59 μs due to efficient quantum confinement. The applications of SiC QDs are demonstrated through labeling A549, HeLa, and NHDF cells and delivering agents for intracellular low-abundant microRNA (miRNA) detection. This advance in preparing photoluminescent SiC QDs is of great significance for broadening their potential in biomedical and optical applications.

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多色荧光碳点调控及其应用EI北大核心CSCD

碳点(carbon dots,CDs)由于具有优异的荧光性能、低毒性、原料广泛、生物相容性好等优点,受到了研究人员的广泛关注。然而,目前大部分CDs的发射波长位于蓝光和绿光的短波长区域,这限制了CDs的广泛应用。多色CDs的合成对长波长CDs合成具有一定的指导作用,并且可以拓宽其应用。因此,本文从CDs的粒径、内部结构和表面态角度阐述了CDs的多色发光机理,综述了实现多色CDs的调控措施(包括反应原料、反应参数、表面改性和分离提纯)及其在发光二极管和生物成像方面的应用。     

Green-emissive carbon quantum dots with high fluorescence quantum yield: Preparation and cell imaging

High fluorescence quantum yield (QY), excellent fluorescence stability, and low toxicity are essential for a good cellular imaging fluorescent probe. Green-emissive carbon quantum dots (CQDs) with many advantages, such as unique fluorescence properties, anti-photobleaching, low toxicity, fine biocompatibility and high penetration depth in tissues, have been considered as a potential candidate in cell imaging fluorescent probes. Herein, N, S-codoped green-emissive CQDs (QY= 64.03%) were synthesized by the one-step hydrothermal method, with m-phenylenediamine as the carbon and nitrogen source, and L-cysteine as the nitrogen and sulfur dopant, under the optimum condition of 200 °C reaction for 2 h. Their luminescence was found to originate from the surface state. In light of the satisfactory photobleaching resistance and the low cytotoxicity, CQDs were used as a cell imaging probe for HeLa cell imaging. The results clearly indicate that cells can be labeled with CQDs, which can not only enter the cytoplasm, but also enter the nucleus through the nuclear pore, showing their broad application prospect in the field of cell imaging.     

Photocurrent imaging of nanocrystal quantum dots on single-walled carbon nanotube device

Semiconductor nanocrystal quantum dots (NQDs) are considered an attractive candidate for use in optoelectronic applications due to the ease of band gap control provided by varying the particle size. To increase the efficiency of NQDs when practically applied in devices, researchers have introduced the concept of coupling of NQDs to one-dimensional nanostructures such as single-walled carbon nanotubes (SWCNTs), which have a ballistic conducting channel. In the present study, NQDs of CdSe core and CdSe/ZnS are used as light absorbing building blocks. SWCNTs and functionalized NQDs are non-covalently coupled using pyridine molecules in order to maintain their electronic structures. To measure the electrical signals from the device, a NQDs-SWCNT hybrid nanostructure is fabricated as a field-effect transistor (FET) using the dielectrophoresis (DEP) method. A confocal scanning microscope was used to scan the devices using a diffraction-limited laser spot and the photocurrent was recorded as a function of the position of the laser spot. To improve the performance of detecting small electronic signal with high signal-to-noise ratio we used a lock-in technique with an intensity-modulated laser. In this paper, we have demonstrated that detection of local photoconductivity provides an efficient means to resolve electronic structure modulations along NQDs-SWCNT hybrid nanostructures.     

Glutathione-capped quantum dots for plasma membrane labeling and membrane potential imaging

Nano Research - The plasma membrane of cells is a crucial biological membrane that involved in a variety of cellular processes including cell signaling transduction through membrane electrical...