Detection of protein molecules by surface‐enhanced Raman spectroscopy‐based immunoassay using 2–5 nm gold nanoparticle lables

Here we report the synthesis of 2–5 nm size gold nanoparticle labels for surface‐enhanced Raman Spectroscopy (SERS) based immunoassay to detect protein molecules. The Au nanoparticles were conjugated with fluorescein isothiocyanate (FITC) and goat anti‐h‐IgG (immunoglobin) and the resultant particles were used for the detection of h‐IgG. Commercially available nitrocellulose strip and silver enhancement method were used for SERS‐based immunoassays. The FITC acts as a Raman probe, and vibrational fingerprint of this molecule was used for the detection of h‐IgG in concentration ranging from 1 to 100 ng/µl. Our Raman probe is robust and small in size and has high water solubility with minimum steric effect during antigen–antibody binding. Copyright © 2007 John Wiley & Sons, Ltd.     

High‐Strength Pressure‐Free Bonding Using Cu and Ni‐Sn Nanoparticles

High‐strength pressure‐free bonding is investigated using Cu nanoparticles as an alternative to conventional solders. Focus is placed on the morphology of Ni‐Sn intermetallic nanoparticles, an additive to a paste of Cu nanoparticles, for improvement of sinterability. The shear strength increases from 23.2 (Cu nanoparticles only) to 31.8 MPa, when 10 wt% of the newly synthesized 15‐nm Ni₃Sn₂ nanocubes is mixed with the Cu nanoparticle paste. This is the first example of the use of base metal nanoparticles under pressure‐free conditions to achieve the bonding strength of an ordinary Pb‐free solder (Sn‐Ag‐Cu). The addition of smaller Ni₃Sn₂ nanocubes 8 nm in size or irregularly shaped Ni₃Sn₂ nanoparticles (25.0 MPa) results in a limited increase in shear strength (26.6 MPa), while the addition of micrometer‐sized Ni₃Sn₂ particles results in a decrease in shear strength (21.5 MPa). The effects of the size and shape of the added Ni₃Sn₂ particles on the shear strength are discussed based on SEM observation of the sintered layers.     

Human‐Serum‐Albumin‐Coated Prussian Blue Nanoparticles as pH‐/Thermotriggered Drug‐Delivery Vehicles for Cancer Thermochemotherapy

Constructing novel multimodal antitumor therapeutic nanoagents has attracted tremendous recent attention. In this work, a new drug‐delivery vehicle based on human‐serum‐albumin (HSA)‐coated Prussian blue nanoparticles (PB NPs) is synthesized. It is demonstrated that doxorubicin (DOX)/HSA is successfully loaded after in situ polymerization of dopamine onto PB NPs, and the PB@PDA/DOX/HSA NPs are highly compatible and stable in various physiological solutions. The NPs possess strong near‐infrared (NIR) absorbance, and excellent capability and stability of photothermal conversion for highly efficient photothermal therapy applications. Furthermore, a bimodal on‐demand drug release sensitively triggered by pH or NIR irradiation has been realized, resulting in a significant chemotherapeutic effect due to the preferential uptake and internalization of the NPs by cancer cells. Importantly, the thermochemotherapy efficacy of the NPs has been examined by a cell viability assay, revealing a remarkably superior synergistic anticancer effect over either monotherapy. Such multifunctional drug‐delivery systems composed of approved materials may have promising biomedical applications for antitumor therapy.     

Nano‐in‐Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

Pulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long‐term safety issues. Formulations of nano‐in‐micro dry powders for lung delivery are engineered using (S)‐ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug‐loaded POxylated polyurea dendrimers coated with chitosan using supercritical‐fluid‐assisted spray drying. The formulations are characterized in terms of morphology, particle‐size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione‐S‐transferase assay. It is demonstrated that ibuprofen‐loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86–3.83 μm), and fine particle fraction (28%–45%), for deposition into the deep lung. The (S)‐ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)‐ibuprofen toxic effect on cancer cellular growth. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10^?3 m ), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.     

Theranostic Iron@Gold Core–Shell Nanoparticles for Simultaneous Hyperthermia‐Chemotherapy upon Photo‐Stimulation

The challenges of nanoparticles, such as size‐dependent toxicity, nonbiocompatibility, or inability to undergo functionalization for drug conjugation, limit their biomedical application in more than one domain. Oval‐shaped iron@gold core–shell (oFe@Au) magnetic nanoparticles are engineered and their applications in magnetic resonance imaging (MRI), optical coherence tomography (OCT), and controlled drug release, are explored via photo stimulation‐generated hyperthermia. The oFe@Au nanoparticles have a size of 42.57 ± 5.99 nm and consist of 10.76 and 89.24 atomic % of Fe and Au, respectively. Upon photo‐stimulation for 10 and 15 minutes, the levels of cancer cell death induced by methotrexate‐conjugated oFe@Au nanoparticles are sixfold and fourfold higher, respectively, than oFe@Au nanoparticles alone. MRI and OCT confirm the application of these nanoparticles as a contrast agent. Finally, results of in vivo experiments reveal that the temperature is elevated by 13.2 °C, when oFe@Au nanoparticles are irradiated with a 167 mW cm^?2 808 nm laser, which results in a significant reduction in tumor volume and scab formation after 7 days, followed by complete disappearance after 14 days. The ability of these nanoparticles to generate heat upon photo‐stimulation also opens new doors for studying hyperthermia‐mediated controlled drug release for cancer therapy. Applications include biomedical engineering, cancer therapy, and theranostics fields.     

Probing Chemical and Mechanical Nanodomains in Copolymer Nanorods with Correlative Atomic Force Microscopy—Nano‐correscopy

The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limited resolution, are unable to map these properties correlatively at nanoscale. An innovative use of atomic force microscopy‐based techniques, namely nano‐correscopy, overcomes this limitation and offers multiprobe capability to map mechanical (viscous and elastic) and chemical domains of nanoparticles correlatively. The strengths of this approach are demonstrated using polymer composite nanorods: m‐PEG‐PLGA ((m‐PEG–methoxy‐poly (ethylene glycol)‐b‐poly (lactic‐co‐glycolic) acid). Precise distribution of PLGA (monomers of lactide and glycolide) and poly(ethylene glycol) (PEG) polymer across nanorods is identified. The hydrophobic lactide component is found predominantly at the apex, while hydrophilic glycolide and PEG assembled at the body of the nanorods and correlate with a gradient of nanomechanical properties. New knowledge of how both nanochemical domains and nanomechanical properties are distributed across the nanorod will allow elucidating the interactions of nanorods with the proteins and biomolecules in the future, which will directly influence the fate of nanorods in vivo and will guide new synthesis methods.     

Antimicrobial and antitumor activities of 1,2,4‐triazoles/polypyrrole chitosan core shell nanoparticles

Combination of natural biodegradable polymer with a synthetic polymer offers excellent properties for the support in drug delivery system. For this purpose, biodegradable conductive nanoparticle polypyrrole based on chitosan (PPC) has been prepared via oxidative polymerization of pyrrole in presence of chitosan using FeCl₃ as oxidant in acidic medium and used as a carrier for 1,2,4‐triazoles. The resultant nanoparticles were characterized by X‐ray diffraction, Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, and thermal gravimetric analysis. The results indicate that spherical nanoparticle of average diameter 52 ± 8 nm was successfully prepared. The spherical particles were composed of dark sphere surrounded by grey shell. A circumferential dark ring is observed in the shell after loading 1,2,4‐triazoles into PPC nanoparticles. The loaded triazoles were released almost linearly against time in a sustained fashion into different pH media. The mechanism of triazoles release was determined using different kinetics equations. The antibacterial activities against the gram‐negative and gram‐positive bacteria were examined. Furthermore, the antitumor activity of PPC nanoparticles loaded 1,2,4‐triazoles was also examined against Ehrlich ascites carcinoma cells and breast cancer cell line (MCF7). Polypyrrole chitosan loaded nanoparticles exhibited higher antitumor activity than 1,2,4‐triazoles.     

Growth profile of stimulated Raman anti‐Stokes scattering influenced by fluorescence seeding in liquid‐core optical fiber

We demonstrated the growth profile of stimulated Raman anti‐Stokes scattering (SRS) of carbon disulfide (CS₂) influenced by fluorescence seeding of all‐trans‐β‐carotene and rhodamine‐B (RhB) in liquid‐core optical fiber (LCOF). The pump energy which was needed to build up the first‐order anti‐Stokes radiation of CS₂ solutions with the fluorescence seeding was lower than that of CS₂ solutions without fluorescence seeding because of the fluorescence enhancement effect on the intensity of the first‐order Stokes radiation. The first‐order anti‐Stokes radiation of the RhB solution (10⁻⁸ M ) was built up at a lower pump energy than that of the all‐trans‐β‐carotene solution (10⁻⁶ M ), and the intensity of the first‐order anti‐Stokes radiation of the RhB solution was higher than that of the all‐trans‐β‐carotene solution. Simultaneously, the coupled wave differential equations were obtained by the theoretical derivation, and the growth profile of the first‐order anti‐Stokes radiation was theoretically calculated with and without the fluorescence seeding by these equations. Copyright © 2009 John Wiley & Sons, Ltd.     

Conformational analysis of 4,4‐dimethyl‐1‐(trifluoromethylsulfonyl)‐1,4‐azasilinane and 2,2,6,6‐tetramethyl‐4‐(trifluoromethylsulfonyl)‐1,4,2,6‐oxazadisilinane

4,4‐Dimethyl‐1‐(trifluoromethylsulfonyl)‐1,4‐azasilinane 1 and 2,2,6,6‐tetramethyl‐4‐(trifluoromethylsulfonyl)‐1,4,2,6‐oxazadisilinane 2 were studied by variable temperature dynamic ¹H, ¹³C, ¹⁹F NMR spectroscopy and theoretical calculations at the DFT (density functional theory) and MP2 (Møller‐Plesset 2) levels of theory. Both kinetic (barriers to ring inversion) and thermodynamic data (frozen conformational equilibria) could be obtained for the two compounds. The computations revealed two minima on the potential energy surface for molecules 1 and 2 corresponding to the rotamers with the CF₃SO₂ group directed ‘inward’ and ‘outward’ the ring, the latter being 0.2–0.4 kcal/mol (for 1 ) and 1.1 kcal/mol (for 2 ) more stable than the former. The vibrational calculations at the DFT and MP2 levels of theory give the values of the free energy difference ΔG^o for the ‘inward’ ‘outward’ equilibrium consistent with those determined from the experimentally measured ratio of the rotamers. The structure of crystalline compound 2 was ascertained by X‐ray diffraction analysis. Copyright © 2011 John Wiley & Sons, Ltd.     

Improved performance of silicon‐nanoparticle film‐coated dye‐sensitized solar cells

Silicon (Si) nanoparticles with average size of 13 nm and orange–red luminescence under UV absorption were synthesized using electrochemical etching of silicon wafers. A film of Si nanoparticles with thickness of 0.75 µm to 2.6 µm was coated on the glass (TiO₂ side) of a dye‐sensitized solar cell (DSSC). The cell exhibited nearly 9% enhancement in power conversion efficiency (η) at film thickness of ～2.4 µm under solar irradiation of 100 mW/cm² (AM 1.5) with improved fill factor and short‐circuit current density. This study revealed for the first time that the Si‐nanoparticle film converting UV into visible light and helping in homogeneous irradiation, can be utilized for improving the efficiency of the DSSCs. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Characterisation of Sonochemically Produced PdO Nanoparticles by X‐ray Absorption Near Edge Structure Spectroscopy

Brij‐35 [polyoxyethylene(23) lauryl ether] stabilised palladium nanoparticles, obtained on attempted sonochemical reduction of PdCl₂ by sodium sulfite in water under Argon, instantaneously oxidized to PdO. The particles obtained were stable and have narrow size distribution with an average size of 10 nm diameter. PdO nanoparticles were reduced to Pd nanoparticles in an autoclave by treatment with 50 bar hydrogen at 140 °C. The catalytic behaviour of Pd nanoparticles, thus obtained, is unusual in comparison with conventional Pd catalysts. The nanoparticles were characterized by UV‐Vis spectroscopy, TEM and their X‐ray Absorption Near Edge Structure (XANES) at the Pd‐L‐III edge.     

Carbon‐Dot‐Decorated Nanodiamonds

The synthesis of a new class of fluorescent carbon nanomaterials, carbon‐dot‐decorated nanodiamonds (CDD‐ND), is reported. These CDD‐NDs are produced by specific acid treatment of detonation soot, forming tiny rounded sp² carbon species (carbon dots), 1–2 atomic layers thick and 1–2 nm in size, covalently attached to the surface of the detonation diamond nanoparticles. A combination of nanodiamonds bonded with a graphitic phase as a starting material and the application of graphite intercalated acids for oxidation of the graphitic carbon is necessary for the successful production of CDD‐ND. The CDD‐ND photoluminescence (PL) is stable, 20 times more intense than the intrinsic PL of well‐purified NDs and can be tailored by changing the oxidation process parameters. Carbon‐dot‐decorated DNDs are shown to be excellent probes for bioimaging applications and inexpensive additives for PL nanocomposites.     

Nano‐Ruby: A Promising Fluorescent Probe for Background‐Free Cellular Imaging

Bioprobes based on fluorescent ruby nanoparticles, which are suitable for ultrasensitive imaging, are reported. A stable aqueous/buffer colloid, permitting facile conjugation to proteins, is produced by femtosecond laser ablation of ruby and the nanoparticles (mean size 17 nm) are photostable, with long lifetime (1–4 ms) 694 nm emission. With time‐gating complete (>20 dB) suppression of cell autofluorescence and suppression of exogenous fluorophores is observed. Nanoparticles are imaged in as‐grown cells and those immunolabeled with quantum dots. Immunoassay binding to target biomolecules is also demonstrated.     

Size and Shape Effect of Gold Nanoparticles in “Far‐Field” Surface Plasmon Resonance

The “far‐field” surface plasmon resonance (FSPR) of metal nanoparticles, which have built a facile way to emission enhancement of red, green, blue, and white with nice reproducibility, has big potential application in solution‐processed organic light‐emitting diodes (OLEDs). According to the theory of the “far‐field” effect, the reflectivity of the metal surface and the phase shift at the reflection play an important role in enhancing ratio, which strongly relate to the size and shape of nanoparticles. In this work, gold nanospheres with different sizes and nanorods are synthesized in order to determine the size and shape effect of FSPR. The results demonstrate that the one with higher reflectivity in a certain range induces a better emission enhancement in the luminous efficiency and the maximum brightness. The nanoparticles with bigger sizes and shape of rods have higher reflectivity, which is consistent with the simulation based on FSPR effect. The phase shifts of different nanoparticles are optimized by the distance between gold nanoparticles and emitters. The metal NPs with a high reflectivity and the applicable phase shift will have big potential for the emission enhancement in OLEDs.     

Enhanced Physiological Stability and Long‐Term Toxicity/Biodegradation In Vitro/In Vivo of Monodispersed Glycerolphosphate‐Functionalized Bioactive Glass Nanoparticles

Monodispersed bioactive glass nanoparticles (BGNs) have received much attention in various biomedical applications such as tissue regeneration, drug/gene delivery, bioimaging, and cancer therapy. However, the poor dispersion stability of BGNs in a physiological environment has limited their wide biomedical applications. The long‐term in vitro/in vivo toxicity and biodegradation of BGNs are also not clear. Monodispersed glycerolphosphate‐functionalized BGNs (GP‐BGN) are synthesized and their stability under physiological environment in vitro, and long‐term biodegradation behavior in vitro and in vivo are investigated herein. GP‐BGN shows significantly enhanced particles stability in physiological environment, good hemocompatibility and cellular biocompatibility, as well as high cellular uptake ability. GP‐BGN also exhibits long‐term biodegradation behavior in vitro/in vivo and negligible biotoxicity (tissue and blood toxicity). This study demonstrates that monodispersed surface‐functionalized BGNs could be used as biocompatible and biodegradable nanomaterials for long‐term safe bioimaging and disease therapy.     

Highly Luminescent Carbon‐Nanoparticle‐Based Materials: Factors Influencing Photoluminescence Quantum Yield

Unravelling the factors influencing photoluminescence (PL) quantum yield of the carbon nanoparticles (CNPs) is the prerequisite for preparing highly luminescent CNP‐based materials. In this work, an easy and effective method is reported for preparing highly luminescent CNP‐based materials. Water‐soluble luminescent CNPs (CNP‐Cs) with large size distribution (1–60 nm) with PL quantum yields of 22% are synthesized through a microwave pyrolysis approach. Energy transfer (ET) is confirmed to occur from small size CNPs (CNP‐Ss:1‐7 nm, blue emitters) to large size CNPs (CNP‐Ls:10–60 nm, green emitters). Further centrifugally separating CNP‐Cs resulted in an enhancement of the PL quantum yield up to 39% of CNP‐Ss aqueous solution. The PL quantum yield of CNP‐Ss could even be further improved in high‐viscosity solvents. PL quantum yield higher than 90% is achieved in films of commercial glue water embedded with the CNP‐Ss at embedding ratio lower than 3 wt%. By contrast, the yield is greatly decreased in the CNP‐C‐embedding films with embedding ratio higher than 1 wt%, which is due to self‐absorption, as well as enhanced ET between CNP‐Ss and CNP‐Ls. High‐viscosity solvents and polymer matrix are proposed to act as surface passivation reagents to enhance PL quantum yield of CNPs.     

Characterization of Nano‐Particles Using Laser‐Induced Incandescence

Laser‐induced incandescence (LII) is introduced as a valuable tool for the characterization of nanoparticles. This optical measurement technique is based on the heating of the particles by a short laser pulse and the subsequent detection of the thermal radiation. It has been applied successfully for the investigation of soot in different fields of application, which is described here in the form of an overview with a focus on work done at the LTT‐Erlangen during the last 10 years. In laboratory flames the soot primary particle size, volume concentration, and relative aggregate size have been determined in combination with the number density of primary particles. Furthermore, the primary particle sizes of carbon blacks have been measured in situ and online under laboratory conditions and also in production reactors. Measurements with different types of commercially available carbon black powders, which were dispersed in a measurement chamber yielded a good correlation between LII results and the specified product properties. Particle diameters determined by LII in a furnace black reactor correlate very well with the CTAB‐absorption number, which is a measure for the specific surface area. It turned out that the LII method is not affected by variations of the aggregate structure of the investigated carbon blacks. The LII signal also contains information on the primary particle size distribution, which can be reconstructed by the evaluation of the signal decay time at, at least, two different time intervals. Additionally, soot mass concentrations have been determined inside diesel engines and online measurements were performed in the exhaust gas of such engines for various engine conditions simultaneously providing information about primary particle size, soot volume, and number concentration. The LII results exhibit good correlation with traditional measurement techniques, e.g., filter smoke number measurements. In addition to the soot measurements, primarily tests with other nanoparticles like TiO₂ or metal particles are encouraging regarding the applicability of the technique for the characterization of such different types of nanoparticles.     

Principal component analysis‐assisted energy dispersive X‐ray fluorescence spectroscopy for non‐invasive quality assurance characterization of complex matrix materials

The analytical challenges in direct quality assurance analysis of complex matrices (extreme matrix effects, spectral overlap, poor signal‐to‐noise ratio (SNR) for trace analytes, ‘dark matrix’, imprecise geometry, need for sample integrity) by energy dispersive X‐ray fluorescence (EDXRF) spectrometry necessitate development of novel techniques for material characterization. We demonstrate the utility of principal component analysis (PCA) in isotope‐excited EDXRF spectrometry of a complex matrix (in this case lubricating oil) in the context of a newly developed EDXRF and scattering (EDXRFS) technique. Lubricating oil quality may be interpreted in terms of its viscosity, anti‐wear, anti‐oxidation, and anti‐rust properties, which are detectable via B, Ca, Mg, Zn, Fe, Na additives (quality markers). Our method involves simultaneous non‐invasive acquisition of both fluorescence and scatter spectra from samples held in a propylene dish, and their modeling in a reduced multidimensional space for an interpretable overview that is analytically more useful than, and complementary to, fluorescence peak‐based quantitation of the additives; by this method, only Fe and Zn are directly detectable, but with SNR of the fluorescence peak 15–20 times poorer compared with analysis after sample digestion. Although Fe and Zn cannot distinguish the various lubricating oil brands, it can differentiate authentic from adulterated. The method was however found to be analytically useful when combined with PCA: various brands of lubricating oil were discriminated in addition to the detection of adulteration. PCA processing of the spectra showed that the most important quality assurance spectral signature information responsible for the success is contained in the scatter region (low‐Z elements). Evaluation of the performance of the method with respect to SNR (i.e. analysis time and therefore speed) showed that there was no significant difference in method performance of analysis live time in the range 100–1000 s, showing proof of concept for rapid characterization of complex matrix materials by PCA‐assisted EDXRFS. Copyright © 2012 John Wiley & Sons, Ltd.     

Rapid detection of 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) using a portable Au‐colloid SERS sensor

In situ rapid detection and identification of polybrominated diphenyl ethers, a group of well‐known persistent organic pollutants, present a great challenge. To develop a portable and sensitive surface‐enhanced Raman scattering (SERS) sensor for rapid 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) detection, we adopted the most commonly used Au nanoparticles, which are effective in the analysis of hydrophobic BDE‐47 with a simple optimization in citrate content and sampling technique. Qualitative and quantitative determination of BDE‐47 was achieved using a portable Raman spectrometer. The SERS response exhibited a linear dependence on the BDE‐47 concentration up to 1000 nM with a detection limit of 75 nM. The density function theory‐calculated Raman spectra agreed well with the experimental observations, and the results justified the existence of electromagnetic enhancement and charge transfer mechanism. This in situ SERS platform allows easy and reliable detection of hydrophobic molecules such as BDE‐47 in complex matrices. Copyright © 2014 John Wiley & Sons, Ltd.