Chitosan nanoparticle as protein delivery carrier - Systematic examination of fabrication conditions for efficient loading and release

Chitosan nanoparticles fabricated via different preparation protocols have been in recent years widely studied as carriers for therapeutic proteins and genes with varying degree of effectiveness and drawbacks. This work seeks to further explore the polyionic coacervation fabrication process, and associated processing conditions under which protein encapsulation and subsequent release can be systematically and predictably manipulated so as to obtain desired effectiveness. BSA was used as a model protein which was encapsulated by either incorporation or incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan-TPP nanoparticles were characterized for particle size, morphology, zeta potential, BSA encapsulation efficiency, and subsequent release kinetics, which were found predominantly dependent on the factors of chitosan molecular weight, chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio. The BSA loaded nanoparticles prepared under varying conditions were in the size range of 200-580 nm, and exhibit a high positive zeta potential. Detailed sequential time frame TEM imaging of morphological change of the BSA loaded particles showed a swelling and particle degradation process. Initial burst released due to surface protein desorption and diffusion from sublayers did not relate directly to change of particle size and shape, which was eminently apparent only after 6 h. It is also notable that later stage particle degradation and disintegration did not yield a substantial follow-on release, as the remaining protein molecules, with adaptable 3-D conformation, could be tightly bound and entangled with the cationic chitosan chains. In general, this study demonstrated that the polyionic coacervation process for fabricating protein loaded chitosan nanoparticles offers simple preparation conditions and a clear processing window for manipulation of physiochemical properties of the nanoparticles (e.g., size and surface charge), which can be conditioned to exert control over protein encapsulation efficiency and subsequent release profile. The weakness of the chitosan nanoparticle system lies typically with difficulties in controlling initial burst effect in releasing large quantities of protein molecules. (C) 2007 Elsevier B.V. All rights reserved.

Novel periodically loaded E-plane filters

Novel E-plane waveguide filters with periodically loaded resonators are proposed. The proposed filters make use of the slow wave effect in order to achieve improved stopband performance and size reduction of roughly 50% without introducing any complexity in the fabrication process. Numerical and experimental results are presented to validate the argument.

Novel periodically loaded ridged waveguide resonators

Novel periodically loaded E-plane waveguide resonators are presented in this paper. The proposed resonators make use of the slow-wave effect in order to achieve significantly increased loaded Q values for resonators of constant volume, as compared to their homogeneous counterparts, without introducing any complexity in the fabrication process. Numerical and experimental results are presented to validate the argument. (C) 2003 Wiley Periodicals, Inc.

Novel periodically loaded multilayer resonators

In this paper novel 3D periodic multilayer structures are investigated in MIC technology, and a periodically loaded multilayer waveguide resonant structure is proposed. This is a very compact structure and still maintains simple fabrication process. The resonator is designed at 10 and 28 GHz. The simulated results of this resonator, which is obtained from commercial FEM software package HFSS, are confirmed by experimental results. The experiments are based oil the same resonator structure, only at 10 GHz. By modifying the conventional waveguide resonator, with the proposed structure, a minimum 30% shorter resonator can be achieved, which is very important at filter applications. (C) 2002 Wiley Periodicals, Inc.

CMOS compatible RF MEMS switches with serpentine springs

This paper describes a serpentine flexure spring design and fabrication process development for radio frequency microelectromechanical (RF MEMS) capacitive switches with coplanar waveguide (CPW) lines. Sputtered tungsten is employed as the CPW line conductor instead of Au, a non-Si compatible material. The bridge membrane is fabricated from Al. The materials and fabrication process can be integrated with CMOS and SOI technology to reduce cost. Results show the MEMS switch has excellent performance with insertion loss 0.3dB, return loss -27dB at 30GHz and high isolation -30dB at 40GHz. The process developed promises to simplify the design and fabrication of RF MEMS on silicon.

Buckling/post-buckling strength of friction stir welded aircraft stiffened panels

Assembling aircraft stiffened panels using friction stir welding offers potential to reduce fabrication time in comparison to current mechanical fastener assembly, making it economically feasible to select structurally desirable stiffener pitching and novel panel configurations. With such a departure from the traditional fabrication process, much research has been conducted on producing strong reliable welds, with less examination of the impact of welding process residual effects on panel structural behaviour and the development of appropriate design methods. This article significantly expands the available panel level compressive strength knowledge, demonstrating the strength potential of a welded aircraft panel with multiple lateral and longitudinal stiffener bays. An accompanying computational study has determined the most significant process residual effects that influence panel strength and the potential extent of panel degradation. The experimental results have also been used to validate a previously published design method, suggesting accurate predictions can be made if the conventional aerospace design methods are modified to acknowledge the welding altered panel properties.

Optical transmission of periodic annular apertures in metal film on high-refractive index substrate: The role of the nanopillar shape

The influence of annular aperture parameters on the optical transmission through arrays of coaxial apertures in a metal film on high refractive index substrates has been investigated experimentally and numerically. It is shown that the transmission resonances are related to plasmonic crystal effects rather than frequency cutoff behavior associated with annular apertures. The role of deviations from ideal aperture shape occurring during the fabrication process has also been studied. Annular aperture arrays are often considered in many applications for achieving high optical transmission through metal films and understanding of nanofabrication tolerances are important. (C) 2010 American Institute of Physics.

Nucleation-Induced Self-Assembly of Multiferroic BiFeO3-CoFe2O4 Nanocomposites

Large areas of perfectly ordered magnetic CoFe2O4 nanopillars embedded in a ferroelectric BiFeO3 matrix were successfully fabricated via a novel nucleation-induced self-assembly process. The nucleation centers of the magnetic pillars are induced before the growth of the composite structure using anodic aluminum oxide (AAO) and lithography-defined gold membranes as hard mask. High structural quality and good functional properties were obtained. Magneto-capacitance data revealed extremely low losses and magneto-electric coupling of about 0.9 mu C/cmOe. The present fabrication process might be relevant for inducing ordering in systems based on phase separation, as the nucleation and growth is a rather general feature of these systems.

Slow Release Drug Dissolution Profile Prediction in Pharmaceutical Manufacturing: a Multivariate and Machine Learning Approach

Slow release drugs must be manufactured to meet target specifications with respect to dissolution curve profiles. In this paper we consider the problem of identifying the drivers of dissolution curve variability of a drug from historical manufacturing data. Several data sources are considered: raw material parameters, coating data, loss on drying and pellet size statistics. The methodology employed is to develop predictive models using LASSO, a powerful machine learning algorithm for regression with high-dimensional datasets. LASSO provides sparse solutions facilitating the identification of the most important causes of variability in the drug fabrication process. The proposed methodology is illustrated using manufacturing data for a slow release drug.

Corrosion Fatigue Behaviour of Laser-welded Shape Memory NiTi Wires in a Simulated Body Fluid

Corrosion fatigue is a fracture process as a consequence of synergistic interactions between the material structure, corrosive environment and cyclic loads/strains. It is difficult to be detected and can cause unexpected failure of engineering components in use. This study reveals a comparison of corrosion fatigue behaviour of laser-welded and bare NiTi wires using bending rotation fatigue (BRF) test coupled with a specifically-designed corrosion cell. The testing medium was Hanks’ solution (simulated body fluid) at 37.5 oC. Electrochemical impedance spectroscopic (EIS) measurement was carried out to monitor the change of corrosion resistance of sample during the BRF test at different periods of time. Experiments indicate that the laser-welded NiTi wire would be more susceptible to the corrosion fatigue attack than the bare NiTi wire. This study can serve as a benchmark for the product designers and engineers to understand the corrosion fatigue behaviour of the NiTi laser weld joint and determine the fatigue life safety factor for NiTi medical devices/implants involving laser welding in the fabrication process.

Plasma chloriding of thin-film silver - A novel process in silver-silver chloride reference electrode fabrication

Silver thin films were modified using a novel plasma modification process for the development of thin-film silver-silver chloride reference electrodes. The surface, physical, and electrochemical properties of these electrodes were investigated by atomic force microscopy, thickness and resistivity measurement techniques, as well as impedance spectroscopy and potentiometry. After plasma treatment, thin-film growth was observed and the electrodes, in general, exhibited low interface impedance and a roughened surface. Evidence of a complex surface reorganization was found. Correlating plasma conditions with film properties suggested that increasing pressure and exposure duration increased species availability, therefore governing the reaction rates, while input power appeared to influence the type of surface chemical reactions. Results also indicated that Ar/Cl-2 mixtures should be employed rather than pure chlorine plasmas. (C) 2002 The Electrochemical Society.

Safe fabrication of sharp gold tips for light emission in scanning tunnelling microscopy

Gold is the optimal tip metal for light emission in scanning tunnelling microscopy (LESTM) under ambient conditions. Sharp Au-tips of similar to 10nm radius were produced reliably using a safe, two-step etching method in 20% (w/w) CaCl2 solution. Previous CaCl2-based methods have tended to produce blunter tips, while other etching techniques that do produce sharp Au-tips, do so with the use of toxic or hazardous electrolytes. The tips are characterised using scanning electron microscopy and their efficacy in LESTM is evidenced by high-resolution, simultaneous topographic and photon mapping of Au(1 1 1)- and polycrystalline Au-surfaces. Spectra of the optical emission exhibit only one or two peaks with etched tips in contrast to the more complex spectra typical of cut tips; this feature, together with the highly symmetric geometry of the tips, facilitates a definitive analysis of the light emission process. (c) 2007 Elsevier B. V.. All rights reserved.

Fabrication and Repair of Cartilage Defects with a Novel Acellular Cartilage Matrix Scaffold

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer, and Triton x 100 solution; molded with freeze-drying process; and cross-linked by ultraviolet irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy and mercury intrusion porosimetry showed that the ACM had a sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the mesenchymal stem cell-ACM constructs had a significant improvement of histological scores when compared to the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics that afford it as a potential scaffold for cartilage tissue engineering.

Fabrication and optical properties of large-scale arrays of gold nanocavities based on rod-in-a-tube coaxials

Centimeter sized arrays of gold coaxial rod-in-a tube cavities have been fabricated using anodized aluminum oxide as a template. The etching process used to create the cavities enables the production of extremely small gaps between tube and rod, on the order of 5 nm, smaller than those created by standard fabrication techniques. Normal incidence spectroscopy reveals two extinction peaks in the visible and near infrared wavelength range associated with resonant plasmonic modes excited in the structure. Numerical simulations show that the modes are associated with in-phase and out-of-phase hybridization of transverse dipolar excitations in the nanorod and in the tube.

Virtual metrology enabled early stage prediction for enhanced control of multi-stage fabrication processes

Semiconductor fabrication involves several sequential processing steps with the result that critical production variables are often affected by a superposition of affects over multiple steps. In this paper a Virtual Metrology (VM) system for early stage measurement of such variables is presented; the VM system seeks to express the contribution to the output variability that is due to a defined observable part of the production line. The outputs of the processed system may be used for process monitoring and control purposes. A second contribution of this work is the introduction of Elastic Nets, a regularization and variable selection technique for the modelling of highly-correlated datasets, as a technique for the development of VM models. Elastic Nets and the proposed VM system are illustrated using real data from a multi-stage etch process used in the fabrication of disk drive read/write heads. © 2013 IEEE.