Synthesis of molecularly imprinted polymer adsorbents for solid-phase extraction of strobilurin fungicides from agricultural products.

Molecularly imprinted polymers for strobilurin fungicides were prepared by precipitation polymerization employing azoxystrobin as template molecular together with methacrylic acid monomer and trimethylolpropane triacrylate cross-linker. Morphological characterization showed molecularly imprinted polymers were uniform spherical particles with about 0.2 µm in diameter, while the morphologies of nonimprinted polymers were irregular bulk. The equilibrium binding and selective experiments proved that molecularly imprinted polymers possessed a higher affinity toward four fungicides compared to nonimprinted polymers and heterogeneous binding sites were found in the molecularly imprinted polymers. Molecularly imprinted solid-phase extraction conditions, including sample loading solvents, selective washing, and elution solvents, were carefully optimized. The developed method showed good recoveries (70.0-114.0%) with relative standard deviations in range of 1.0-9.8% (n  = â€¯3) for samples (cucumber and peach) spiked at three different levels (10, 50, and 100 µg/ kg). The detection limit (signal/noise = 3) ranged from 0.01 to 0.08 µg/kg. The results demonstrated good potential use of this convenient and highly efficient method for determining trace strobilurin fungicides in agricultural products.

Ti-O-N/Ti composite coating on Ti-6Al-4V: surface characteristics, corrosion properties and cellular responses.

To enhance the corrosion resistance of Ti-6Al-4V and extend its lifetime in medical applications, Ti-O-N/Ti composite coating was synthesized on the surface via plasma immersion ion implantation and deposition (PIIID). Surface morphology and cross sectional morphology of the composite coating were characterized using atomic force microscopy and scanning electron microscopy, respectively. Although X-ray photoelectron spectroscopic analysis revealed that the Ti-O-N/Ti composite coating was composed of non-stoichiometric titanium oxide, titanium nitride and titanium oxynitride, no obvious characteristic peak corresponding to the crystalline phases of them was detected in the X-ray diffraction pattern. In accordance with Owens-Wendt equation, surface free energy of the uncoated and coated samples was calculated and compared. Moreover, the corrosion behavior of uncoated and coated samples was evaluated by means of electrochemical impedance spectroscopy measurement, and an equivalent circuit deriving from Randles model was used to fit Bode plots and describe the electrochemical processes occurring at the sample/electrolyte interface. On the basis of the equivalent circuit model, the resistance of the composite coating was 4.7 times higher than that of the passive layer on uncoated samples, indicating the enhanced corrosion resistance after PIIID treatment. Compared to uncoated Ti-6Al-V, Ti-O-N/Ti-coated samples facilitated ostoblast proliferation within 7 days of cell culture, while there was no statistically significant difference in alkaline phosphate activity between uncoated and coated samples during 21 days of cell culture.

Preparation of metal-organic framework @molecularly imprinted polymers for extracting N-nitrosamines in salted vegetables.

In this paper, the novel metal-organic framework @molecularly imprinted polymers were prepared and applied in extracting N-nitrosamines from salted vegetables. The imprinted polymers were coated on the surface of MIL-101 using multi-dummy template molecules (5-nonanol, benzhydrol and N-formylpyrrolidine). The characterization and adsorbing experiments showed that the hybrid imprinted polymers presented spherical particles with typically core-shell structure, and exhibited high adsorption capacity (maximum capacity: 46.85 mg/g) and fast equilibrium rate (only 5 min) for N-nitrosamines. Various parameters (sample loading solvent, pH, washing solvent, elution solvent and elution volume) affecting solid-phase extraction were optimized. Under the optimum conditions, the solid-phase extraction process based on the hybrid polymers combined with high performance liquid chromatography-ultraviolet detection method was established and applied to analyze N-nitrosamines in different salted vegetables. The results showed that the developed method produced the linear relationship between the peak areas versus the N-nitrosamines concentrations of 0.2-10 µg/g with limit of detections from 20.6 to 76.1 ng/g. The spiked recovery of N-nitrosamines in the salted vegetable samples was in the range of 66-100.5 % with relative standard deviation from 0.1 to 3.4 %. Those results demonstrated that the established method was sensitive and efficient for directly enriching and analyzing trace N-nitrosamines in salted vegetables.

Synthesis of metal-organic framework @molecularly imprinted polymer adsorbents for solid phase extraction of organophosphorus pesticides from agricultural products.

The novel core-shell structural zeolitic imidazolate framework-8 @molecularly imprinted polymers were successfully synthesized by surface imprinting technique and used as adsorbents for solid-phase extraction of organophosphorus pesticides. The obtained hybrid composites were characterized by scanning electron microscopy, transmission electron microscopy and Fourier-transform infrared, and their adsorbing and recognition performance were evaluated by binding experiments. The results showed that zeolitic imidazolate framework-8 @molecularly imprinted polymers presented a typically core-shell structure with molecularly imprinted shell (about 50 nm) homogeneously polymerized on the surface of zeolitic imidazolate framework-8 core, and exhibited specific recognition towards organophosphorus pesticides with fast adsorption capacity. The adsorption and desorption conditions including sample loading solvent, sample pH, washing and elution solvent were optimized. Under optimum conditions, the solid-phase extraction based on zeolitic imidazolate framework-8 @molecularly imprinted polymers combined with high liquid chromatography-tandem mass spectrometry method for determining organophosphorus pesticides was established and exhibited good linearity (R2 ≥ 0.9927) in the range of 1-200 µg/L. With spiked at three different concentration levels in agricultural products (cauliflower, radish, pear, muskmelon), the recoveries ranged from 82.5% to 123.0% with relative standard deviations lower than 8.24%. The developed method was sensitive, convenient and efficient. More importantly, this study could provide a promising strategy for designing new adsorbents with extremely fast mass transfer rate for other potential trace contaminants.

Preparation of metal-organic framework @molecularly imprinted polymers for extracting strobilurin fungicides from agricultural products.

The core-shell metal-organic framework coated with molecularly imprinted polymers (ZIF-8@MIPs) were successfully synthesized by surface imprinting technique, and applied as adsorbents for solid-phase extraction of strobilurin fungicides. The obtained hybrid complex was characterized in detail, and their adsorbing and recognition performance were evaluated. The results showed that ZIF-8@MIPs presented typically core-shell structure with MIP shell (about 20 nm), and exhibited larger adsorption capacity (102.5 mg g-1) and fast adsorption ability (only 5 min). Under the optimized conditions, a sensitive, efficient and reliable method for determining six strobilurin fungicides in different agricultural products based on ZIF-8@MIPs coupling with high performance liquid chromatography-tandem mass spectrometry was established. This method showed good linearity with correlation coefficients higher than 0.9990. With spiked at three different concentration levels in agricultural products (apple, pear, banana, Chinese cabbage, cabbage, cucumber), the good recoveries (83.5-129.0%) with relative standard deviations from 0.5 to 10.2% were obtained. The limit of detections and the limit of quantifications were 0.01-1.12 ng g-1 and 0.03-3.73 ng g-1, respectively. Those results demonstrated good potential application of ZIF-8@MIPs for enriching and separating trace strobilurin fungicides in agricultural samples.

Precise modeling of complex tooth surface microtopography and multi-degree-of-freedom nonlinear friction dynamics for high-performance face gear.

Face gear transmission is a kind of space-meshing mechanism that is mainly used in the field of aviation. Compared with traditional transmission, it has the advantages of stability, reliability, low noise, and strong carrying capacity. However, owing to its complex tooth surface, there are no means to accurately model the face gear. Likewise, research based on the geometry is difficult. Therefore, the tooth surface equation of the face gear is derived in this article based on the meshing theory. Based on the equations, the point cloud of the face gear tooth surface is calculated, the complex tooth surface is generated, and the face gear is accurately modeled. Moreover, taking tooth surface friction excitation into consideration, a multi-degree-of-freedom nonlinear dynamic model of face gear transmission system is established, using the adaptive variable step length Runge-Kutta method. As shown in the results, the bifurcation diagram, phase diagram, time history diagram, and Poincaré section diagram are combined to analyze the influence of tooth surface friction and meshing frequency on the dynamic characteristics of the system.

Synthesis of dummy-template molecularly imprinted polymer adsorbents for solid phase extraction of aminoglycosides antibiotics from environmental water samples.

A novel dummy molecularly imprinted polymers (DMIPs) for aminoglycoside antibiotics (AAs) was prepared for the first time by precipitation polymerization using raffinose as template molecule, methacrylic acid as functional monomer and trimethylolpropane triacrylate as cross-linker. The obtained DMIPs were characterized in detail, and their adsorbing and recognition performance were evaluated. The results showed that the DMIPs exhibited specific recognition towards six AAs with large adsorption capacity. The dummy molecularly imprinted solid phase extraction (DMISPE) conditions including elution/washing solutions and sample loading volumes were optimized. Under optimum conditions, a convenient and efficient method for the determination of AAs in environmental water samples based on DMISPE coupling with hydrophilic interaction-high performance liquid chromatography-tandem mass spectrometry was established. The developed method showed good linearity with correlation coefficients higher than 0.9921 for all the analytes and good recoveries (70.8-108.3%) with relative standard deviations from 2.6 to 11.4% spiked at three different concentration levels in water samples. The limit of detection (S/N = 3) ranged from 0.006 to 0.6 ng/mL. The results demonstrated good potential of DMIPs for sample pretreatment of trace AAs in environmental water samples.

Distribution of silicone oil in prefilled glass syringes probed with optical and spectroscopic methods.

Prefilled glass syringes (PFSs) have become the most commonly used device for the delivery of recombinant protein therapeutics in parenteral formulations. In particular, auto-injectors preloaded with PFSs greatly facilitate the convenient and efficient self-administration of protein therapeutics by patients. Silicone oil is used as a lubricant in PFSs to facilitate the smooth motion of the plunger during injection. However, there have been few sophisticated analytical techniques that can qualitatively and quantitatively characterize in-situ the morphology, thickness, and distribution of silicone oil in PFSs. In this paper, we demonstrate the application of three optical techniques including confocal Raman microscopy, Schlieren optics, and thin film interference reflectometry to visualize and characterize silicone oil distribution in PFS. The results showed that a container coating process could produce unevenly distributed silicone oil on the glass barrel of PFSs. An insufficiency of the amount of silicone oil on the glass barrel of a PFS can cause stalling when the device is preloaded into an auto-injector. These analytical techniques can be applied to monitor the silicone oil distribution in PFSs.

Microspectroscopic investigation of the membrane clogging during the sterile filtration of the growth media for mammalian cell culture.

Growth media for mammalian cell culture are very complex mixtures of several dozens of ingredients, and thus the preparation of qualified media is critical to viable cell density and final product titers. For liquid media prepared from powdered ingredients, sterile filtration is required prior to use to safeguard the cell culture process. Recently one batch of our prepared media failed to pass through the sterile filtration due to the membrane clogging. In this study, we report the root cause analysis of the failed sterile filtration based on the investigations of both the fouling media and the clogged membranes with multiple microspectroscopic techniques. Cellular particles or fragments were identified in the fouling media and on the surfaces of the clogged membranes, which were presumably introduced to the media from the bacterial contamination. This study demonstrated that microspectroscopic techniques may be used to rapidly identify both microbial particles and inorganic precipitates in the cell culture media.

Free fatty acid particles in protein formulations, part 1: microspectroscopic identification.

We report, for the first time, the identification of fatty acid particles in formulations containing the surfactant polysorbate 20. These fatty acid particles were observed in multiple mAb formulations during their expected shelf life under recommended storage conditions. The fatty acid particles were granular or sand-like in morphology and were several microns in size. They could be identified by distinct IR bands, with additional confirmation from energy-dispersive X-ray spectroscopy analysis. The particles were readily distinguishable from protein particles by these methods. In addition, particles containing a mixture of protein and fatty acids were also identified, suggesting that the particulation pathways for the two particle types may not be distinct. The techniques and observations described will be useful for the correct identification of proteinaceous versus nonproteinaceous particles in pharmaceutical products.

Tooth hard tissue stimulates bone remodeling as a potential motive force during tooth eruption.

Tooth eruption is an orientating action which migrates teeth coronally during life, even in bone or after occlusion contact is lost. The eruption pathway is due to bone resorption near the enamel crown and bone deposition around the cementum-covered roots. Due to their proximity to bone resorption and deposition, we hypothesize that the hard tissues enamel, dentine or cementum are important during eruption. In the present study, extracted human teeth were cut into enamel samples, enamel-dentine samples or dentine-cementum samples, and implanted into bone defects in rabbit tibia. Hematoxylin and eosin, tartrate-resistant acid phosphatase activity, tetracycline tracing and scanning electron microscopy were used to investigate bone resorption and deposition 1-8 weeks after surgery. The results showed that resorption lacunae with numerous osteoclasts were observed facing enamel and significant new bone deposition occurred near the cementum surface, compared to other hard tooth surfaces. These findings indicate that the enamel crown may stimulate bone resorption and initiate the eruption pathway, and that the cementum root may stimulate bone deposition. Bone regeneration initiated by tooth hard tissues may be a potential motive force during tooth eruption.

Identification of a mixed microparticle by combined microspectroscopic techniques: a real forensic case study in the biopharmaceutical industry.

Identification of foreign microparticles in drug products is one of the first steps in evaluating the nature of particle contamination and its consequences for product quality. To characterize various foreign particles, we use spectral database search methods as well as a number of microscopic and microspectroscopic techniques. Here, we report a case study involving the identification and root-cause investigation of a microparticle consisting of four compounds. Foreign microparticles consisting of mixtures pose unique challenges for identification as their spectra are difficult to interpret and general database searches usually return unsatisfactory results. Moreover, sample separation through purification and other manipulations is time consuming and often difficult for these microparticles due to their small sizes and the limited quantities of the components. Here we demonstrate an applicable methodology that combines multiple microscopic and microspectroscopic techniques to identify a heterogeneous microparticle without the need for sample purification or chemical separation. This methodology primarily combines Raman, infrared, and energy dispersive X-ray microspectroscopic techniques to obtain complementary spectral information for the identification of heterogeneous particles. With this methodology, the mixed microparticle investigated in this study was determined to consist of polyisobutylene, hydrated magnesium silicate, titanium dioxide, and silica, likely originating from the vial stopper material.

Raman microscopic applications in the biopharmaceutical industry: in situ identification of foreign particulates inside glass containers with aqueous formulated solutions.

Particle identification is an important analytical procedure for quality control and assurance in the biopharmaceutical industry. Rapid and reliable identification of micro-particles helps in evaluating the nature of particle contamination and its consequences on the product quality regulated by internal and external standards. Raman microscopy is one of the microspectroscopic techniques that can be used to identify micro-particles with the advantage of in situ detection. In this paper we demonstrate that a visible laser Raman microscope was particularly useful to identify micro-particles that were inside glass containers such as glass syringes, vials, and test tubes, which are commonly used as containers for aqueous formulated drugs. The examples include the identifications of a droplet-like particle inside a pre-filled glass syringe, a fibrous particle inside a glass test tube, and a white particle inside a glass vial; all of these examples usually demand challenging or time-consuming sample manipulation for other techniques. The Raman microscopic technique was shown to be able to solve these challenging micro-particle identifications due to its ability to carry out detection in situ. Particularly in the example of micro-droplet identification, the Raman microscopic technique was the only choice for a fast and successful particle detection. For all three identifications, Raman in situ detection has significantly accelerated particle analysis and avoided potential sample secondary contamination or losses owing to none or minimal sample manipulation.