The electronic structure of Au25 clusters: between discrete and continuous.

Here, an approach based on synchrotron resonant photoemission is employed to explore the transition between quantization and hybridization of the electronic structure in atomically precise ligand-stabilized nanoparticles. While the presence of ligands maintains quantization in Au25 clusters, their removal renders increased hybridization of the electronic states in the vicinity of the Fermi level. These observations are supported by DFT studies.

Space and time-resolved probing of heterogeneous catalysis reactions using lab-on-a-chip.

Probing catalytic reactions on a catalyst surface in real time is a major challenge. Herein, we demonstrate the utility of a continuous flow millifluidic chip reactor coated with a nanostructured gold catalyst as an effective platform for in situ investigation of the kinetics of catalytic reactions by taking 5-(hydroxymethyl)furfural (HMF) to 2,5-furandicarboxylic acid (FDCA) conversion as a model reaction. The idea conceptualized in this paper can not only dramatically change the ability to probe the time-resolved kinetics of heterogeneous catalysis reactions but also used for investigating other chemical and biological catalytic processes, thereby making this a broad platform for probing reactions as they occur within continuous flow reactors.

Gold-silica quantum rattles for multimodal imaging and therapy.

Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell's central cavity. This "quantum rattle" structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.

Computational investigations of the mixing performance inside liquid slugs generated by a microfluidic T-junction.

Droplet-based microfluidics has gained extensive research interest as it overcomes several challenges confronted by conventional single-phase microfluidics. The mixing performance inside droplets/slugs is critical in many applications such as advanced material syntheses and in situ kinetic measurements. In order to understand the effects of operating conditions on the mixing performance inside liquid slugs generated by a microfluidic T-junction, we have adopted the volume of fluid method coupled with the species transport model to study and quantify the mixing efficiencies inside slugs. Our simulation results demonstrate that an efficient mixing process is achieved by the intimate collaboration of the twirling effect and the recirculating flow. Only if the reagents are distributed transversely by the twirling effect, the recirculating flow can bring in convection mechanism thus facilitating mixing. By comparing the mixing performance inside slugs at various operating conditions, we find that slug size plays the key role in influencing the mixing performance as it determines the amount of fluid to be distributed by the twirling effect. For the cases where short slugs are generated, the mixing process is governed by the fast convection mechanism because the twirling effect can distribute the fluid to the flow path of the recirculating flow effectively. For cases with long slugs, the mixing process is dominated by the slow diffusion mechanism since the twirling effect is insufficient to distribute the large amount of fluid. In addition, our results show that increasing the operating velocity has limited effects on improving the mixing performance. This study provides the insight of the mixing process and may benefit the design and operations of droplet-based microfluidics.

Chemically induced magnetism in atomically precise gold clusters.

Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications.

Millifluidics for chemical synthesis and time-resolved mechanistic studies.

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Ligand-stabilized and atomically precise gold nanocluster catalysis: a case study for correlating fundamental electronic properties with catalysis.

We present results from our investigations into correlating the styrene-oxidation catalysis of atomically precise mixed-ligand biicosahedral-structure [Au25(PPh3)10(SC12H25)5Cl2](2+) (Au25-bi) and thiol-stabilized icosahedral core-shell-structure [Au25(SCH2CH2Ph)18](-) (Au25-i) clusters with their electronic and atomic structure by using a combination of synchrotron radiation-based X-ray absorption fine-structure spectroscopy (XAFS) and ultraviolet photoemission spectroscopy (UPS). Compared to bulk Au, XAFS revealed low Au-Au coordination, Au-Au bond contraction and higher d-band vacancies in both the ligand-stabilized Au clusters. The ligands were found not only to act as colloidal stabilizers, but also as d-band electron acceptor for Au atoms. Au25-bi clusters have a higher first-shell Au coordination number than Au25-i, whereas Au25-bi and Au25-i clusters have the same number of Au atoms. The UPS revealed a trend of narrower d-band width, with apparent d-band spin-orbit splitting and higher binding energy of d-band center position for Au25-bi and Au25-i. We propose that the differences in their d-band unoccupied state population are likely to be responsible for differences in their catalytic activity and selectivity. The findings reported herein help to understand the catalysis of atomically precise ligand-stabilized metal clusters by correlating their atomic or electronic properties with catalytic activity.

Lab-on-a-chip synthesis of inorganic nanomaterials and quantum dots for biomedical applications.

The past two decades have seen a dramatic raise in the number of investigations leading to the development of Lab-on-a-Chip (LOC) devices for synthesis of nanomaterials. A majority of these investigations were focused on inorganic nanomaterials comprising of metals, metal oxides, nanocomposites and quantum dots. Herein, we provide an analysis of these findings, especially, considering the more recent developments in this new decade. We made an attempt to bring out the differences between chip-based as well as tubular continuous flow systems. We also cover, for the first time, various opportunities the tools from the field of computational fluid dynamics provide in designing LOC systems for synthesis inorganic nanomaterials. Particularly, we provide unique examples to demonstrate that there is a need for concerted effort to utilize LOC devices not only for synthesis of inorganic nanomaterials but also for carrying out superior in vitro studies thereby, paving the way for faster clinical translation. Even though LOC devices with the possibility to carry out multi-step syntheses have been designed, surprisingly, such systems have not been utilized for carrying out simultaneous synthesis and bio-functionalization of nanomaterials. While traditionally, LOC devices are primarily based on microfluidic systems, in this review article, we make a case for utilizing millifluidic systems for more efficient synthesis, bio-functionalization and in vitro studies of inorganic nanomaterials tailor-made for biomedical applications. Finally, recent advances in the field clearly point out the possibility for pushing the boundaries of current medical practices towards personalized health care with a vision to develop automated LOC-based instrumentation for carrying out simultaneous synthesis, bio-functionalization and in vitro evaluation of inorganic nanomaterials for biomedical applications.

Millifluidics for time-resolved mapping of the growth of gold nanostructures.

Innovative in situ characterization tools are essential for understanding the reaction mechanisms leading to the growth of nanoscale materials. Though techniques, such as in situ transmission X-ray microscopy, fast single-particle spectroscopy, small-angle X-ray scattering, etc., are currently being developed, these tools are complex, not easily accessible, and do not necessarily provide the temporal resolution required to follow the formation of nanomaterials in real time. Here, we demonstrate for the first time the utility of a simple millifluidic chip for an in situ real time analysis of morphology and dimension-controlled growth of gold nano- and microstructures with a time resolution of 5 ms. The structures formed were characterized using synchrotron radiation-based in situ X-ray absorption spectroscopy, 3-D X-ray tomography, and high-resolution electron microscopy. These gold nanostructures were found to be catalytically active for conversion of 4-nitrophenol into 4-aminophenol, providing an example of the potential opportunities for time-resolved analysis of catalytic reactions. While the investigations reported here are focused on gold nanostructures, the technique can be applied to analyze the time-resolved growth of other types of nanostructured metals and metal oxides. With the ability to probe at least a 10-fold higher concentrations, in comparison with traditional microfluidics, the tool has potential to revolutionize a broad range of fields from catalysis, molecular analysis, biodefense, and molecular biology.

Local Structure of ZnO micro flowers and nanoparticles obtained by micro-segmented flow synthesis.

The micro-segmented flow technique was applied for continuous synthesis of ZnO micro- and nanoparticles with short residence times of 9.4 s and 21.4 s, respectively. The obtained particles were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Small angle X-ray scattering (SAXS) and photoluminescence spectroscopy were used to determine the size and optical properties of ZnO nanoparticles. In addition, extended X-ray absorption fine structure (EXAFS) spectroscopy was employed to investigate local structural properties. The EXAFS measurements reveal a larger degree of structural disorder in the nanoparticles than the microparticles. These structural changes should be taken into consideration while evaluating the size-dependent visible emission of ZnO nanoparticles.

Developing a millifluidic platform for the synthesis of ultrasmall nanoclusters: ultrasmall copper nanoclusters as a case study.

The future of lab-on-a-chip devices for the synthesis of nanomaterials hinges on the successful development of high-throughput methods with better control over their size. While significant effort in this direction mainly focuses on developing "difficult to fabricate" complex microfluidic reactors, scant attention has been paid to the "easy to fabricate" and simple millifluidic systems that could provide the required control as well as high throughput. By utilizing numerical simulation of fluids within the millifluidic space at different flow rates, the results presented here show velocity profiles and residence time distributions similar to the case of microfluidics. By significantly reducing the residence time and residence time distribution, a continuous flow synthesis of ultrasmall copper nanoclusters (UCNCs) with exceptional colloidal stability is achieved. In-situ synchrotron-radiation-based X-ray absorption spectroscopy (XAS) reveal that the as-prepared clusters are about 1 nm, which is further supported by transmission electron microscopy and UV-vis spectroscopy studies. The clusters reported here are the smallest ever produced using a lab-on-a-chip platform. When supported on silica, they are found to efficiently catalyze C-H oxidation reactions, hitherto unknown to be catalyzed by Cu. This work suggests that a millifluidic platform can be an inexpensive, versatile, easy-to-use, and powerful tool for nanoparticle synthesis in general, and more specifically for ultrasmall nanoclusters (UNCs).

Synthesis, characterization, and testing of supported Au catalysts prepared from atomically-tailored Au38(SC12H25)24 clusters.

Nearly monodispersed Au(38)(SC(12)H(25))(24) clusters (1.7 ± 0.2 nm) were synthesized using a modified Brust process while utilizing a "thiol etching" approach for the ligand exchange. HRTEM, MALDI, FTIR, and XAS analysis confirmed the formation of the 38-atom clusters in solution. This solution was used to impregnate a microporous TiO(2) support to give 0.7% Au(38)/TiO(2) catalyst. Subsequent drying in air and treatment with H(2)/He at 400 °C removed most of the sulfur ligands, and also increased the Au cluster size to 3.9 ± 0.96 nm. XPS and EXAFS analysis of this supported catalyst showed trace levels of residual sulfides, apparently located at the Au-TiO(2) interface. CO oxidation tests on these supported clusters show an activation energy and range of TOFs comparable to those reported by others. These results suggest that supported Au clusters of controllable size can be prepared with this thiol-ligated solution-based method, providing a new approach to the synthesis of these catalysts.

Size evolution of gold nanoparticles in a millifluidic reactor.

The size evolution of gold nanoparticles in a millifluidic reactor is investigated using spatially resolved transmission electron microscopy (TEM). The experimental data is supported by numerical simulations, carried out to study the residence-time distribution (RTD) of tracers that have the same properties as Au ions. Size and size distribution of the particles within the channels are influenced by the mixing zones as well as the RTD. However, the Au nanoparticles obtained show a broader size distribution even at the shortest investigated residence time of 3.53 s, indicating that in addition to surface growth reaction kinetics also plays an important role. The comparison of time resolved particle growth within the millifluidic channel with flask-based reactions reveals that the particle size can be controlled better within millifluidic channels. Overall, the results indicate potential opportunities to utilize easy to fabricate millifluidic reactors for the synthesis of nanoparticles, as well as as for carrying out time resolved kinetic studies.

Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery.

Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term "hyperthermia" in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term "hyperthermia" by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled drug delivery through bond breaking (DBB) and hyperthermia-based controlled drug delivery through enhanced permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms--towards successful application in personalized medicine.

Influence of Gold Nanoshell on Hyperthermia of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs).

Gold nanoshell around super paramagnetic iron oxide nanoparticles (SPIONs) was synthesized and small angle X-ray scattering (SAXS) analysis suggests a gold coating of approximately 0.4 to 0.5 nm thickness. On application of low frequency oscillating magnetic fields (44 - 430 Hz), a four- to five-fold increase in the amount of heat released with gold-coated SPIONs (6.3 nm size) in comparison with SPIONs (5.4 nm size) was observed. Details of the influence of frequencies of oscillating magnetic field, concentration and solvent on heat generation are presented. We also show that, in the absence of oscillating magnetic field, both SPIONs and SPIONs@Au are not particularly cytotoxic to mammalian cells (MCF-7 breast carcinoma cells and H9c2 cardiomyoblasts) in culture, as indicated by the reduction of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium by viable cells in a phenazine methosulfate-assisted reaction.

Molecular MRI for sensitive and specific detection of lung metastases.

Early and specific detection of metastatic cancer cells in the lung (the most common organ targeted by metastases) could significantly improve cancer treatment outcomes. However, the most widespread lung imaging methods use ionizing radiation and have low sensitivity and/or low specificity for cancer cells. Here we address this problem with an imaging method to detect submillimeter-sized metastases with molecular specificity. Cancer cells are targeted by iron oxide nanoparticles functionalized with cancer-binding ligands, then imaged by high-resolution hyperpolarized (3)He MRI. We demonstrate in vivo detection of pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The method not only holds promise for cancer imaging but more generally suggests a fundamentally unique approach to molecular imaging in the lungs.

Microfluidic synthesis of nanomaterials.

An overview of the current information and analyses on the microfluidic synthesis of different types of nanomaterial, including metallic and silica nanoparticles and quantum dots, is presented. Control of particle size, size distribution, and crystal structure of nanomaterials are examined in terms of the special features of microfluidic reactors.

Glutaric acid as a spacer facilitates improved intracellular uptake of LHRH-SPION into human breast cancer cells.

Superparamagnetic iron oxide nanoparticles (SPIONs) bound directly to luteinizing hormone releasing hormone (LHRH) have shown high efficiency for intracellular uptake to breast cancer cells, MDA-MB-435S.luc. We demonstrate in this communication that inclusion of a small spacer molecule such as glutaric acid (Glu) in between SPION and LHRH increases further receptor mediated intracellular uptake. LHRH-bound SPIONs with and without the spacer molecule were nontoxic.

LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases.

Targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) could facilitate their accumulation in metastatic cancer cells in peripheral tissues, lymph nodes and bones and enhance the sensitivity of magnetic resonance imaging (MRI). The specificities of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone/chorionic gonadotropin (LH/CG)- bound SPIONs were tested in human breast cancer cells in vitro and were found to be dependent on the receptor expression of the target cells, the time of incubation and showed saturation kinetics. In incubations with MDA-MB-435S.luc cells, the highest iron accumulation was 452.6 pg Fe/cell with LHRH-SPIONs, 203.6 pg Fe/cell with beta-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 degrees C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (betaCG or LHRH) decreased the iron accumulation in each case. LHRH-SPIONs were poorly incorporated by macrophages. Tumors and metastatic cells from breast cancer xenografts were targeted in vivo in a nude mouse model. LHRH-SPION specifically accumulated in cells of human breast cancer xenografts. The amount of LHRH-SPION in the lungs was directly dependent on the number of metastatic cells and amounted to 77.8 pg Fe/metastastic cell. In contrast, unconjugated SPIONs accumulated in the liver, showed poor affinity to the tumor, and were not detectable in metastatic lesions in the lungs. LHRH-SPION accumulated in the cytosolic compartment of the target cells and formed clusters. LHRH-SPIONs did not accumulate in livers of normal mice. In conclusion, LHRH conjugated SPIONs may serve as a contrast agent for MR imaging in vivo and increase the sensitivity for the detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs.

Functionalization of gold and glass surfaces with magnetic nanoparticles using biomolecular interactions.

Advances in nanotechnology have enabled the production and characterization of magnetic particles with nanometer-sized features that can be functionalized with biological recognition elements for numerous applications in biotechnology. In the present study, the synthesis of and interactions between self-assembled monolayers (SAMs) on gold and glass surfaces and functionalized magnetic nanoparticles have been characterized. Immobilization of 10-15 nm streptavidin-functionalized nanoparticles to biotinylated gold and glass surfaces was achieved by the strong interactions between biotin and streptavidin. Fluorescent streptavidin-functionalized nanoparticles, biotinylated surfaces, and combinations of the two were characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electron and fluorescent microscopy to confirm that little or no functionalization occurred in nonbiotinylated regions of the gold and glass surfaces compared to the biotinylated sites. Together these techniques have potential use in studying the modification and behavior of functionalized nanoparticles on surfaces in biosensing and other applications.