Smart Iterative Analysis Tool for the Size Distribution of Spherical Nanoparticles.

The size of nanoparticles is a critical parameter with regard to their performance. Therefore, precise measurement of the size distribution is often required. While electron microscopy (EM) is a useful tool to image large numbers of particles at once, manual analysis of individual particles in EM images is a time-consuming and labor-intensive task. Therefore, reliable automatic detection methods have long been desired. This paper introduces a novel automatic particle analysis software package based on the circular Hough transform (CHT). Our software package includes novel features to enhance precise particle analysis capabilities. We applied the CHT algorithm in an iterative workflow, which ensures optimal detection over wide radius intervals, to deal with overlapping particles. In addition, smart intensity criteria were implemented to resolve common difficult cases that lead to false particle detection. Implementing these criteria enabled an effective and precise analysis by minimizing detection of false particles. Overall, our approach showed reliable particle analysis results by resolving common types of particle overlaps and deformation with only negligible errors.

Influence of Process Parameters on the Kinetics of the Micelle-to-Vesicle Transition and Ripening of Polystyrene-Block-Polyacrylic Acid.

Due to their ability to self-assemble into complex structures, block copolymers are of great interest for use in a wide range of future applications, such as self-healing materials. Therefore, it is important to understand the mechanisms of their structure formation. In particular, the process engineering of the formation and transition of the polymer structures is required for ensuring reproducibility and scalability, but this has received little attention in the literature. In this article, the influence of the addition rate of the selective solvent on the homogeneity of self-assembled vesicles of polystyrene-block-polyacrylic acid is demonstrated, as well as the influence of the reaction time and the mixing intensity on the morphology of the polymer structures. For example, it was demonstrated that the higher the mixing intensity, the faster the transition from micelle to vesicle. The experimental results are further supported by CFD simulations, which visually and graphically show an increase in shear rate and narrower shear rate distributions at higher stirring rates. Furthermore, it was demonstrated that the vesicle size is not only kinetically determined, since flow forces above a critical size lead to the deformation and fission of the vesicles.

Conducting ITO Nanoparticle-Based Aerogels-Nonaqueous One-Pot Synthesis vs. Particle Assembly Routes.

Indium tin oxide (ITO) aerogels offer a combination of high surface area, porosity and conductive properties and could therefore be a promising material for electrodes in the fields of batteries, solar cells and fuel cells, as well as for optoelectronic applications. In this study, ITO aerogels were synthesized via two different approaches, followed by critical point drying (CPD) with liquid CO2. During the nonaqueous one-pot sol-gel synthesis in benzylamine (BnNH2), the ITO nanoparticles arranged to form a gel, which could be directly processed into an aerogel via solvent exchange, followed by CPD. Alternatively, for the analogous nonaqueous sol-gel synthesis in benzyl alcohol (BnOH), ITO nanoparticles were obtained and assembled into macroscopic aerogels with centimeter dimensions by controlled destabilization of a concentrated dispersion and CPD. As-synthesized ITO aerogels showed low electrical conductivities, but an improvement of two to three orders of magnitude was achieved by annealing, resulting in an electrical resistivity of 64.5-1.6 kΩ·cm. Annealing in a N2 atmosphere led to an even lower resistivity of 0.2-0.6 kΩ·cm. Concurrently, the BET surface area decreased from 106.2 to 55.6 m2/g with increasing annealing temperature. In essence, both synthesis strategies resulted in aerogels with attractive properties, showing great potential for many applications in energy storage and for optoelectronic devices.

Preparation of Self-Assembled Nanoparticle-Polymer Hybrids from Modified Silica Nanoparticles and Polystyrene-Block-Polyacrylic Acid Vesicles via the Co-Precipitation Method.

Nanoparticle-polymer hybrids are becoming increasingly important because seemingly contrasting properties, such as mechanical stability and high elasticity, can be combined into one material. In particular, hybrids made of self-assembled polymers are of growing interest since they exhibit high structural precision and diversity and the subsequent reorganization of the nanoparticles is possible. In this work, we show, for the first time, how hybrids of silica nanoparticles and self-assembled vesicles of polystyrene-block-polyacrylic acid can be prepared using the simple and inexpensive method of co-precipitation, highlighting in particular the challenges of using silica instead of other previously well-researched materials, such as gold. The aim was to investigate the influence of the type of modification and the particle size of the silica nanoparticles on the encapsulation and structure of the polymer vesicles. For this purpose, we first needed to adjust the surface properties of the nanoparticles, which we achieved with a two-step modification procedure using APTES and carboxylic acids of different chain lengths. We found that silica nanoparticles modified only with APTES could be successfully encapsulated, while those modified with APTES and decanoic acid resulted in vesicle agglomeration and poor encapsulation due to their strong hydrophobicity. In contrast, no negative effects were observed when different particle sizes (20 nm and 45 nm) were examined.

Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels.

Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile.

Backscattering-Based Discrimination of Microparticles Using an Optofluidic Multiangle Scattering Chip.

In this research, we designed and fabricated an optofluidic chip for the detection and differentiation of single particles via the combination of backscattered (BSC) and forward-scattered (FSC) or side-scattered (SSC) light intensity. The high sensitivity of BSC light to the refractive index of the particles enabled an effective approach for the differentiation of individual particles based on the type of material. By recording BSC as well as FSC and SSC light intensities from single particles, transiting through the illumination zone in a microfluidic channel, the size and type of material could be detected simultaneously. The analysis of model samples of polystyrene (PS), as a primary microplastic particle, and silica microspheres showed substantially higher BSC signal values of PS because of a larger refractive index compared to the silica. The scatter plots correlating contributions of BSC (FSC-BSC and SSC-BSC) allowed a clear differentiation of PS and silica particles. To demonstrate the great potential of this methodology, two "real-life" samples containing different types of particles were tested as application examples. Commercial toothpaste and peeling gel products, as primary sources of microplastics into effluents, were analyzed via the optofluidic chip and compared to results from scanning electron microscopy. The scattering analysis of the complex samples enabled the detection and simultaneous differentiation of particles such as microplastics according to their differences in the refractive index via distinctive areas of high and low BSC signal values. Hence, the contribution of BSC light measurements in multiangle scattering of single particles realized in an optofluidic chip opens the way for the discrimination of single particles in a liquid medium in manifold fields of application ranging from environmental monitoring to cosmetics.

Phase Transitions of Polarised PVDF Films in a Standard Curing Process for Composites.

The article reports on the influence of annealing PVDF in an autoclave process on the PVDF phase composition. DSC, FTIR and XRD measurements serve to observe the phase changes in an already stretched, polarised and ß-phase rich film. Annealing was conducted between 90 and 185 ∘C to cover a broad range of curing processes in an autoclave. The ß-phase is found to be stable up to near the melting range at 170 ∘C. At 175 ∘C, the non-piezoelectric α-phase dominates and the piezoelectric γ- and γ'-phases appear. The γ-phase grows at elevated temperatures and replaces the ß-phase. This observation stresses the importance of developing new methods to reactivate the polarisation after annealing, in particular for the integration of PVDF as a sensor in laminated structures, such as CFRP.

Magnetic Nanoparticle-Based Dianthin Targeting for Controlled Drug Release Using the Endosomal Escape Enhancer SO1861.

Targeted tumor therapy can provide the basis for the inhibition of tumor growth. However, a number of toxin-based therapeutics lack efficacy because of insufficient endosomal escape after being internalized by endocytosis. To address this problem, the potential of glycosylated triterpenoids, such as SO1861, as endosomal escape enhancers (EEE) for superparamagnetic iron oxide nanoparticle (SPION)-based toxin therapy was investigated. Herein, two different SPION-based particle systems were synthesized, each selectively functionalized with either the targeted toxin, dianthin-epidermal growth factor (DiaEGF), or the EEE, SO1861. After applying both particle systems in vitro, an almost 2000-fold enhancement in tumor cell cytotoxicity compared to the monotherapy with SPION-DiaEGF and a 6.7-fold gain in specificity was observed. Thus, the required dose of the formulation was appreciably reduced, and the therapeutic window widened.

Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma.

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.

In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy.

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

Effect of the Anionic Counterpart: Molybdate vs. Tungstate in Energy Storage for Pseudo-Capacitor Applications.

Nickel-based bimetallic oxides (BMOs) have shown significant potential in battery-type electrodes for pseudo-capacitors given their ability to facilitate redox reactions. In this work, two bimetallic oxides, NiMoO4 and NiWO4, were synthesized using a wet chemical route. The structure and electrochemical properties of the pseudo-capacitor cathode materials were characterized. NiMoO4 showed superior charge storage performance in comparison to NiWO4, exhibiting a discharge capacitance of 124 and 77 F.g-1, respectively. NiMoO4, moreover, demonstrates better capacity retention after 1000 cycles with 87.14% compared to 82.22% for NiWO4. The lower electrochemical performance of the latter was identified to result from the redox behavior during cycling. NiWO4 reacts in the alkaline solution and forms a passivation layer composed of WO3 on the electrode, while in contrast, the redox behavior of NiMoO4 is fully reversible.

Comprehensive Characterization of APTES Surface Modifications of Hydrous Boehmite Nanoparticles.

Hydrous boehmite (γ-AlOOH) nanoparticles (BNP) show great potential as nanoscale filler for the fabrication of fiber reinforced nanocomposite materials. Notably, the particle-matrix interaction has been demonstrated to be decisive for improving the matrix-dominant mechanical properties in the past years. Tailoring the surface properties of the nanofiller enables to selectively design the interaction and thus to exploit the benefits of the nanocomposite in an optimal way. Here, an extensive study is presented on the binding of (3-aminopropyl)triethoxysilane (APTES), a common silane surface modifier, on BNP in correlation to different process parameters (concentration, time, temperature, and pH). Furthermore, a comprehensive characterization of the modified BNP was performed by using elemental analysis (EA), thermogravimetric analysis (TGA) coupled with mass spectrometry (TGA-MS), and Kaiser's test (KT). The results show an increasing monolayer formation up to a complete surface coverage with rising APTES concentration, time, and temperature, resulting in a maximal grafting density of 1.3 molecules/nm2. Unspecific multilayer formation was solely observed under acidic conditions. Comparison of TGA-MS results with data recorded from EA, TGA, and KT verified that TGA-MS is a convenient and highly suitable method to elucidate the ligand binding in detail.

Exchange Bias in FePt-FePt3 Thin Films by Controlled Phase Transition of Blended Nanoparticle Building Blocks.

Nanostructured composite thin films showing magnetic exchange coupling at the material interface have attracted great interest for the development of electronic components such as spin-valves. Besides the commonly performed fabrication of multilayer systems, the utilization of nanoparticle building blocks holds great potential for thin films with tailored magnetic properties and allows the facile but controlled combination of materials with complementary magnetic characteristics. In this work, we present the use of prefabricated highly crystalline iron platinum (fcc-FePt) and iron oxide (FexOy) nanoparticles for the preparation of nanocomposite thin films with varying compositions by wet processing from mixed dispersions. The resulting multiphase coatings showed high homogeneity, low surface roughness, and superparamagnetic behavior. By the variation of the amount of incorporated iron oxide, a precise adjustment of the magnetization at high field strength could be achieved. Furthermore, calcination under inert gas atmosphere resulted in a controlled phase transition of the magnetic phases and thus, in purely metallic coatings composed of ferromagnetic fct-FePt and antiferromagnetic fcc-FePt3, a decrease in surface roughness as well as high magnetic coercivity at room temperature. Field-cooling below the Néel temperature of fcc-FePt3 led to an exchange bias effect with a strong increase in coercivity and the characteristic hysteresis shift. In comparison to the literature, our nanocomposite thin films showed fully ordered phases without the occurrence of phase impurities, a distinctly higher coercivity, and an exchange bias shift of 38.7 mT.

Step-by-step monitoring of a magnetic and SERS-active immunosensor assembly for purification and detection of tau protein.

We report a bottom-up synthesis of iron oxide and gold nanoparticles, which are functionalized and combined to form a nanohybrid serving as an immune sensor, which selectively binds to tau protein, a biomarker for diagnosis of Alzheimer's disease. Detection of the target analyte is achieved by surface-enhanced Raman scattering originating from the diagnostic part of the nanohybrid that was prepared from Au nanoparticles functionalized with 5,5'-dithiobis-(2-nitrobenzoic acid) as a Raman reporter and monoclonal anti-tau antibody. The magnetic part consists of Fex Oy nanoparticles functionalized with polyclonal anti-tau antibody and is capable to separate tau protein from a complex matrix such as cerebrospinal fluid. We further identified and validated a set of analytical tools that allow monitoring the success of both nanoparticle preparation and each functionalization step performed during the assembly of the two binding sites by an immune reaction. By applying UV/Vis spectroscopy, dynamic light scattering, zeta potential measurements, X-ray diffraction, small-angle X-ray scattering, and transmission electron microscopy, we demonstrate a proof-of-concept for a controlled and step-by-step traceable synthesis of a tau protein-specific immune sensor.

Spray-Dried Hierarchical Aggregates of Iron Oxide Nanoparticles and Their Functionalization for Downstream Processing in Biotechnology.

In this work, the structuring of iron oxide nanoparticles via spray-drying (SD) of aqueous suspensions is investigated, leading to micrometer-sized aggregates with saturation magnetization comparable to that of the individual nanoparticles. Interestingly, the superparamagnetic behavior is retained despite the multicore structure. Modification of the aggregates via the addition of silica nanoparticles to the suspension allows for control of the resulting magnetization by adjusting the iron oxide content. Moreover, the morphology of the produced aggregates is gradually shifted from irregular inflated-like shapes in case of pure iron oxide aggregates to reach spherical structures when bringing the silica content to only 20%. The aggregates with different magnetization can be effectively separated in a simple column with an attached permanent magnet. Functionalization of pure iron oxide aggregates with a previously coupled ligand holding a nitrilotriacetic acid (NTA)-like moiety and subsequent loading with Ni2+ ions leads to the ability to bind 6-histidine (His6)-tagged target proteins via chelation complexes for magnetic separation. The application of the presented system for the purification of recombinant protein A in multiple cycles is shown. The recyclability of the separation system in combination with the high degree of magnetic separation is promising for future applications in the field of preparative in situ protein purification.

Rapid Microfluidic Preparation of Niosomes for Targeted Drug Delivery.

Niosomes are non-ionic surfactant-based vesicles with high promise for drug delivery applications. They can be rapidly prepared via microfluidics, allowing their reproducible production without the need of a subsequent size reduction step, by controlled mixing of two miscible phases of an organic (lipids dissolved in alcohol) and an aqueous solution in a microchannel. The control of niosome properties and the implementation of more complex functions, however, thus far are largely unknown for this method. Here we investigate microfluidics-based manufacturing of topotecan (TPT)-loaded polyethylene glycolated niosomes (PEGNIO). The flow rate ratio of the organic and aqueous phases was varied and optimized. Furthermore, the surface of TPT-loaded PEGNIO was modified with a tumor homing and penetrating peptide (tLyp-1). The designed nanoparticular drug delivery system composed of PEGNIO-TPT-tLyp-1 was fabricated for the first time via microfluidics in this study. The physicochemical properties were determined through dynamic light scattering (DLS) and zeta potential analysis. In vitro studies of the obtained formulations were performed on human glioblastoma (U87) cells. The results clearly indicated that tLyp-1-functionalized TPT-loaded niosomes could significantly improve anti-glioma treatment.

Secondary Particle Formation during the Nonaqueous Synthesis of Metal Oxide Nanocrystals.

This study aims to elucidate the aggregation and agglomeration behavior of TiO2 and ZrO2 nanoparticles during the nonaqueous synthesis. We found that zirconia nanoparticles immediately form spherical-like aggregates after nucleation with a homogeneous size of 200 nm, which can be related to the metastable state of the nuclei and the reduction of surface free energy. These aggregates further agglomerate, following a diffusion-limited colloid agglomeration mechanism that is additionally supported by the high fractal dimension of the resulting agglomerates. In contrast, TiO2 nanoparticles randomly orient and follow a reaction-limited colloid agglomeration mechanism that leads to a dense network of particles throughout the entire reaction volume. We performed in situ laser light transmission measurements and showed that particle formation starts earlier than previously reported. A complex population balance equation model was developed that is able to simulate particle aggregation as well as agglomeration, which eventually allowed us to distinguish between both phenomena. Hence, we were able to investigate the respective agglomeration kinetics with great agreement to our experimental data.

Non-Aqueous Sol-Gel Synthesis of FePt Nanoparticles in the Absence of In Situ Stabilizers.

The synthesis of FePt nanocrystals is typically performed in an organic solvent at rather high temperatures, demanding the addition of the in situ stabilizers oleic acid and oleylamine to produce monomodal particles with well-defined morphologies. Replacing frequently-used solvents with organic media bearing functional moieties, the use of the stabilizers can be completely circumvented. In addition, various morphologies and sizes of the nanocrystals can be achieved by the choice of organic solvent. The kinetics of particle growth and the change in the magnetic behavior of the superparamagnetic FePt nanocrystals during the synthesis with a set of different solvents, as well as the resulting morphologies and stoichiometries of the nanoparticles were determined by powder X-ray diffraction (PXRD), small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP-OES)/mass spectrometry (ICP-MS), and superconducting quantum interference device (SQUID) measurements. Furthermore, annealing of the as-prepared FePt nanoparticles led to the ordered L10 phase and, thus, to hard magnetic materials with varying saturation magnetizations and magnetic coercivities.

Selective manipulation of superparamagnetic nanoparticles for product purification and microfluidic diagnostics.

The needs of scalable product purification as well as the demand for sensitive diagnostics for highly dilute entities can be addressed with the utilization of tailored superparamagnetic nanoparticles. Recent developments have led to more efficient fluidic systems at different scales with suspended nanoparticles or nanoparticle aggregates. However, magnetic nanoparticle systems differ widely in properties and their applications are characterized by very specific challenges. This review summarizes advances in the synthesis of superparamagnetic particles and displays states and trends in research making use of these particles in biotechnological downstream processing and in biosensing.

In situ affinity purification of his-tagged protein A from Bacillus megaterium cultivation using recyclable superparamagnetic iron oxide nanoparticles.

This paper discusses the use of recyclable functionalized nanoparticles for an improved downstream processing of recombinant products. The Gram-positive bacterium Bacillus megaterium was used to secrete recombinant protein A fused to a histidine tag into the culture supernatant in shaker flasks. Superparamagnetic iron oxide nanoparticles functionalized with 3-glycidoxypropyl-trimethoxysilane-coupled-nitrilotriacetic-acid groups (GNTA-SPION) were synthesized and added directly to the growing culture. After 10min incubation time, >85% of the product was adsorbed onto the particles. The particles were magnetically separated using handheld neodymium magnets and the product was eluted. The GNTA-SPION were successfully regenerated and reused in five consecutive cycles. In the one-step purification, the purity of the product reached >99.9% regarding protein A. A very low particle concentration of 0.5g/L was sufficient for effective product separation. Bacterial growth was not influenced negatively by this concentration. Particle analysis showed similar properties between freshly synthesized and regenerated GNTA-SPION. The overall process efficiency was however influenced by partial disintegration of particle agglomerates and thus loss of particles. The demonstration of very fast in situ product removal from growing bacterial culture combined with a very high product purity within one step shows possibilities for automated large scale purification combined with recycling of biomass.