Multi-functional chitosan nanoparticles encapsulating quantum dots and Gd-DTPA as imaging probes for bio-applications

Chitosan was used to encapsulate both CdSe/ZnS quantum dots (QDs) and the magnetic resonance imaging (MRI) contrast agent gadolinium-diethylenetriaminepentaacetate (Gd-DTPA), forming multi-functional nanoparticles that can be used in a wide range of in vitro or in vivo studies as fluorescent biological labels as well as MRI contrast agents, respectively. Multi-color QDs at pre-determined molar ratios were encapsulated into chitosan nanoparticles to produce bar-coding fluorescent labels. The encapsulated QDs and Gd-DTPA still maintained their desirable optical properties and relatively high relaxivity, respectively. The chitosan nanoparticles also showed good aqueous stability and enhanced biocompatibility on myoblast cells.     

Polyamine-functionalized carbon quantum dots as fluorescent probes for selective and sensitive detection of copper ions

A novel sensing system has been designed for Cu(2+) ion detection based on the quenched fluorescence (FL) signal of branched poly(ethylenimine) (BPEI)-functionalized carbon quantum dots (CQDs). Cu(2+) ions can be captured by the amino groups of the BPEI-CQDs to form an absorbent complex at the surface of CQDs, resulting in a strong quenching of the CQDs' FL via an inner filter effect. Herein, we have demonstrated that this facile methodology can offer a rapid, reliable, and selective detection of Cu(2+) with a detection limit as low as 6 nM and a dynamic range from 10 to 1100 nM. Furthermore, the detection results for Cu(2+) ions in a river water sample obtained by this sensing system agreed well with that by inductively couple plasma mass spectrometry, suggesting the potential application of this sensing system.     

CdSe/CdS semiconductor quantum rods as robust fluorescent probes for paraffin-embedded tissue imaging

Immunofluorescence techniques on formalin fixed paraffin-embedded sections allow for the evaluation of the expression and spatial distribution of specific markers in patient tissue specimens or for monitoring the fate of labeled cells after in vivo injection. This technique suffers however from the auto-fluorescence background signal of the embedded tissue that eventually confounds the analysis. Here we show that rod-like semiconductor nanocrystals (QRs), intramuscularly injected in living mice, could be clearly detected by confocal microscopy in formalin fixed paraffin-embedded tissue sections. Despite the low amount of QRs amount injected (25 picomoles), these were clearly visible after 24 h in the muscle sections and their fluorescence signal was stronger than that of CdSe/ZnS quantum dots (QDs) similarly functionalized and in the case of QRs only, the signal lasted even after 21 days after the injection.     

Perovskite quantum dots as fluorescent materials for multi-colored lighting

Halide perovskite quantum dots (PQDs) have been intensively studied because of their superior optical properties and have great potential applications in laser, display technology and light-emitting diodes (LEDs). Presently, high-efficiency green emissive CH₃NH₃PbBr₃ PQDs have been successfully fabricated. However, the synthesis of stable iodide-based CH₃NH₃PbX₃ (MAPbX₃ (X?=?Cl, Br, I), MA?=?CH₃NH₃) QDs still faces significant challenges because they are sensitive to the moisture in open air. Herein, we investigated the effect of the solvent and ligand on the growth of the as-prepared MAPbBr₃ and MAPbI₃ sample, mainly involved in the volume ratio of N,N-dimethylformamide (DMF) and γ-butyrolactone (GBL) and the amount of n-octylamine in toluene. The results show that the low volume ratio of DMF and GBL is beneficial to prepare highly luminescent, stable and full-colored MAPbX₃ PQDs in open air. Besides, the PL emission peak of MaPbBr₃ PQDs can be adjusted from 430 to 513 nm via precisely controlling the amount of n-octylamine in toluene because of quantization. The obtained MAPbX₃ PQDs show high quantum yield and a wide range of tunable light emission from ultraviolet to near-infrared region. The MAPbX₃ PQDs, especially iodide-based MAPbX₃ PQDs, obtained from this method remain stable more than 3 months at ambient condition. We further demonstrated the multi-colored LEDs by using different color emissive MAPbX₃ PQDs as color converters and being subjected to excitation through a blue GaN chip. Furthermore, MAPbX₃ PQDs are expected to show interesting nanoscale optical properties and have great potential applications in electroluminescence devices, lasers and optical sensors.     

Calixarene capped quantum dots as luminescent probes for Hg ions

Luminescent and stable CdSe/ZnS core/shell quantum dots (QDs) capped with sulfur calixarene are prepared for the selective determination of mercury ions in acetonitrile with high sensitivity.     

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.     

A general route to efficient functionalization of silicon quantum dots for high-performance fluorescent probes

A general technique for efficient surface modification of silicon nanocrystals is highly desirable for the development of silicon quantum dots (SiQDs) as fluorescent probes for biological applications. Herein, a facile microwave-assisted hydrosilylation process for the preparation of stable SiQDs in a single step is presented. FTIR spectroscopy indicates that molecules with various terminal functionalities, such as alcohol, alkyl groups, and carboxylic acid, are grafted successfully onto the surface of silicon nanocrystals. The dispersibility of such SiQDs is clearly dependent on the terminal functional groups of the grafted molecules. In addition, the as-prepared SiQDs show excellent cell compatibility, photoluminescence properties, and stability, and their use as long-term intracellular fluorescent probes is also demonstrated. It is envisaged that this facile and effective method for the stabilization and functionalization of SiQDs with tailored wetting and chemical properties will enable wide application of SiQDs in a number of areas.     

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     

Versatile immunosensor using CdTe quantum dots as electrochemical and fluorescent labels

A versatile immunosensor using CdTe quantum dots as electrochemical and fluorescent labels has been developed for sensitive protein detection. This sandwich-type sensor is fabricated on an indium tin oxide chip covered with a well-ordered gold nanoparticle monolayer. Gel imaging systems were successfully introduced to develop a novel high-efficient optical immunoassay, which could perform simultaneous detection for the samples with a series of different concentrations of a target analyte. The linear range of this assay was between 0.1 and 500 ng/mL, and the assay sensitivity could be further increased to 0.005 ng/mL with the linear range from 0.005 to 100 ng/mL by stripping voltammetric analysis. The immunosensor showed good precision, high sensitivity, acceptable stability, and reproducibility and could be used for the detection of real sample with consistent results in comparison with those obtained by the ELISA method.     

Exploring feasibility of multicolored CdTe quantum dots for in vitro and in vivo fluorescent imaging

We report the use of novel multicolored CdTe quantum dots (QDs) as fluorophores for biological fluorescence imaging. The CdTe QDs were prepared to exhibit emission wavelengths in the green, yellow, and red range by using trifluoroacetic acid (TFA), L-cysteine and thioglycolic acid (TGA) as surface stabilizers, respectively. The particles have good water solubility and photostability. Fluorescence imaging potential was evaluated in vitro and in vivo using a multispectral Maestro CRI Fluorescence Imaging system. The results show that different colored CdTe QDs allow sensitive detection simultaneously or separately both in vitro and in vivo against background fluorescence. The studies indicate that CdTe QDs can provide alternative fluorescent probes for biological imaging.     

Bioconjugated fluorescent zeolite L nanocrystals as labels in protein microarrays

Zeolite L nanocrystals, as inorganic host material containing hydrophobic fluorophore N,N'-bis(2,6-dimethylphenyl)perylene-3,4,9,10-tetracarboxylic diimide in the unidirectional channels, are developed as new labels for biosensor systems. The external surface of the particles is modified with carboxylic acid groups for conjugation to primary amines of biomolecules such as antibodies. Anti-digoxigenin (anti-DIG) is selected to be immobilized on zeolite L via N-hydroxysulfosuccinimide ester linker. Together with DIG, it serves as a good universal binding pair for diverse analyte detection owing to the high binding affinity and low background noise. The conjugates are characterized by the dynamic light scattering technique for their hydrodynamic diameters and by enzyme-linked immunosorbent assay for antigen-antibody binding behavior. The characterizations prove that anti-DIG antibodies are successfully immobilized on zeolite L with their binding activities maintained. The microarray fluorescent sandwich immunoassay based on such nanocrystalline labels shows high sensitivity in a thyroid-stimulating hormone assay with the lower detection limit down to the femtomolar range. These new fluorescent labels possess great potential for in vitro diagnostics applications.     

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.     

Evaluation of red CdTe and near infrared CdHgTe quantum dots by fluorescent imaging

Non-invasive fluorescent imaging of preclinical animal models in vivo is a rapidly developing field with new emerging technologies and techniques. Quantum dot (QD) fluorescent probes with longer emission wavelengths in red and near infrared (NIR) emission ranges are more amenable to deep-tissue imaging, because both scattering and autofluorescence are reduced as wavelengths are increased. We have designed and synthesized red CdTe and NIR CdHgTe QDs for fluorescent imaging. We demonstrated fluorescent imaging by using CdTe and CdHgTe QDs as fluorescent probes both in vitro and in vivo. Both CdTe and CdHgTe QDs provided sensitive detection over background autofluorescence in tissue biopsies and live mice, making them attractive probes for in vivo imaging extending into deep tissues or whole animals. The studies suggest a basis of using QD-antibody conjugates to detect membrane antigens.     

Preparation and characterization of highly luminescent water-soluble CdTe quantum dots as optical temperature probes

Highly luminescent water-soluble CdTe quantum dots were synthesized with an electrogenerated precursor. The size, morphology, optical properties as well as fluorescence stability were characterized by transmission electron microscope, high-resolution transmission electron microscope, powder X-ray diffraction, UV-vis-NIR spectrophotometer, and fluorescence spectrophotometer. The results show that the CdTe QDs with diameter ranging from 2.0 nm to 3.5 nm have good crystallizability, high quantum yield and favorable fluorescence stability. Moreover, the CdTe QDs demonstrate temperature-dependent reversible PL intensity variations at moderate temperatures above room temperature. It is also found that the QDs with different sizes possess different sensitivity to the temperature. All the studies indicate that the CdTe QDs are expected to be promising candidates for a variety of biological and biomedical applications.     

Graded-index fiber lens proposed for ultrasmall probes used in biomedical imaging

The quality and parameters of probing optical beams are extremely important in biomedical imaging systems both for image quality and light coupling efficiency considerations. For example, the shape, size, focal position, and focal range of such beams could have a great impact on the lateral resolution, penetration depth, and signal-to-noise ratio of the image in optical coherence tomography. We present a beam profile characterization of different variations of graded-index (GRIN) fiber lenses, which were recently proposed for biomedical imaging probes. Those GRIN lens modules are made of a single mode fiber and a GRIN fiber lens with or without a fiber spacer between them. We discuss theoretical analysis methods, fabrication techniques, and measured performance compared with theory.     

Highly fluorescent fluoride-responsive hydrogels embedded with CdTe quantum dots

Functionalized CdTe quantum dots (QDs) synthesized via ion exchange demonstrated a selective response toward fluoride in aqueous solutions based on a rapid sol-gel transition that was visible to the naked eye. The fluoride-induced hydrogel exhibited excellent fluorescent performance because of the incorporation of QDs. As a result, this highly fluorescent fluoride-induced hydrogel may pave a new way to sense fluoride using a visible sol-gel transition.