Optimized design of high power mid-infrared Er3+, Pr3+ -codoped ZBLAN fiber laser

Based on the rate equations describing the operation of the Er3+, Pr3+ -codoped ZBLAN fiber lasers with different pump configurations, theoretical calculations that relate to the population characteristics and optimization of CW operation of high power Er3+, Pr3+ :ZBLAN double-clad fiber lasers are presented. Using the measured ET (energy-transfer), ETU (energy-transfer-upconversion) and CR (cross-relaxation) parameters relevant to Er3+, Pr3+ -codoped ZBLAN, a good agreement between the theoretical results from the model and recently reported experimental measurements is obtained. The effects on the slope efficiency of a number of laser parameters including fiber length, reflectance of the output mirror and pumping configuration are quantitatively analyzed and used for the design and optimization of high power Er3+, Pr3+ -codoped ZBLAN fiber lasers.

Design and development of cationic liposomes as DNA vaccine adjuvants

Cationic liposomes have been extensively explored for their efficacy in delivering nucleic acids, by offering the ability to protect plasmid DNA against degradation, promote gene expression and, in the case of DNA vaccines, induce both humoural and cellular immune responses. DNA vaccines may also offer advantages in terms of safety, but they are less effective and need an adjuvant to enhance their immunogenicity. Therefore, cationic liposomes can be utilised as delivery systems and/or adjuvants for DNA vaccines to stimulate stronger immune responses. To explore the role of liposomal systems within plasmid DNA delivery, parameters such as the effect of lipid composition, method of liposome preparation and presence of electrolytes in the formulation were investigated in characterisation studies, in vitro transfection studies and in vivo biodistribution and immunisation studies. Liposomes composed of 1,2-dioleoyl-sn-glycero 3-phosphoethanolamine (DOPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3- trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method and hydrated in aqueous media with or without presence of electrolytes. Whilst the in vitro transfection efficiency of all liposomes resulted to be higher than Lipofectin, DSTAP-based liposomes showed significantly higher transfection efficiency than DOTAP-based formulations. Furthermore, upon intramuscular injection of liposomal DNA vaccines, DSTAP-based liposomes showed a significantly stronger depot effect at the injection site. This could explain the result of heterologous immunisation studies, which revealed DSTAP-based liposomal vaccines induce stronger immune responses compared to DOTAP-based formulations. Previous studies have shown that having more liposomally associated antigen at the injection site would lead to more drainage of them into the local lymph nodes. Consequently, this would lead to more antigens being presented to antigen presenting cells, which are circulating in lymph nodes, and this would initiate a stronger immune response. Finally, in a comparative study, liposomes composed of dimethyldioctadecylammonium bromide (DDA) in combination with DOPE or immunostimulatory molecule of trehalose 6,6-dibehenate (TDB) were prepared and investigated in vitro and in vivo. Results showed that although DDA:TDB is not able to transfect the cells efficiently in vitro, this formulation induces stronger immunity compared to DDA:DOPE due to the immunostimulatory effects of TDB. This study demonstrated, while the presence of electrolytes did not improve immune responses, small unilamellar vesicle (SUV) liposomes induced stronger humoural immune responses compared to dehydration rehydration vesicle (DRV) liposomes. Moreover, lipid composition was shown to play a key role in in vitro and in vivo behaviour of the formulations, as saturated cationic lipids provided stronger immune responses compared to unsaturated lipids. Finally, heterologous prime/boost immunisation promoted significantly stronger immune responses compared to homologous vaccination of DNA vaccines, however, a single immunisation of subunit vaccine provoked comparable levels of immune response to the heterologous regimen, suggesting more immune efficiency for subunit vaccines compared to DNA vaccines.

The accuracy of parameter estimation from noisy data, with application to resonance peak estimation in distributed Brillouin sensing

Distributed Brillouin sensing of strain and temperature works by making spatially resolved measurements of the position of the measurand-dependent extremum of the resonance curve associated with the scattering process in the weakly nonlinear regime. Typically, measurements of backscattered Stokes intensity (the dependent variable) are made at a number of predetermined fixed frequencies covering the design measurand range of the apparatus and combined to yield an estimate of the position of the extremum. The measurand can then be found because its relationship to the position of the extremum is assumed known. We present analytical expressions relating the relative error in the extremum position to experimental errors in the dependent variable. This is done for two cases: (i) a simple non-parametric estimate of the mean based on moments and (ii) the case in which a least squares technique is used to fit a Lorentzian to the data. The question of statistical bias in the estimates is discussed and in the second case we go further and present for the first time a general method by which the probability density function (PDF) of errors in the fitted parameters can be obtained in closed form in terms of the PDFs of the errors in the noisy data.

Optimized design of high power mid-infrared Er3+, Pr3+ -codoped ZBLAN fiber laser

Based on the rate equations describing the operation of the Er3+, Pr3+ -codoped ZBLAN fiber lasers with different pump configurations, theoretical calculations that relate to the population characteristics and optimization of CW operation of high power Er3+, Pr3+ :ZBLAN double-clad fiber lasers are presented. Using the measured ET (energy-transfer), ETU (energy-transfer-upconversion) and CR (cross-relaxation) parameters relevant to Er3+, Pr3+ -codoped ZBLAN, a good agreement between the theoretical results from the model and recently reported experimental measurements is obtained. The effects on the slope efficiency of a number of laser parameters including fiber length, reflectance of the output mirror and pumping configuration are quantitatively analyzed and used for the design and optimization of high power Er3+, Pr3+ -codoped ZBLAN fiber lasers.

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics.

Design of multilevel amplitude regenerative system

We propose a scheme for multilevel (nine or more) amplitude regeneration based on a nonlinear optical loop mirror (NOLM) and demonstrate through numerical modeling its efficiency and cascadability on circular 16-, 64-, and 256- symbol constellations. We show that the amplitude noise is efficiently suppressed. The design is flexible and enables variation of the number of levels and their positioning. The scheme is compatible with phase regenerators. Also, compared to the traditional single-NOLM configuration scheme, new features, such as reduced and sign-varied power-dependent phase shift, are available. The model is simple to implement, as it requires only two couplers in addition to the traditional NOLM, and offers a vast range of optimization parameters. © 2014 Optical Society of America.

Multi-frequency segmental bio-impedance device:design, development and applications

Bio-impedance analysis (BIA) provides a rapid, non-invasive technique for body composition estimation. BIA offers a convenient alternative to standard techniques such as MRI, CT scan or DEXA scan for selected types of body composition analysis. The accuracy of BIA is limited because it is an indirect method of composition analysis. It relies on linear relationships between measured impedance and morphological parameters such as height and weight to derive estimates. To overcome these underlying limitations of BIA, a multi-frequency segmental bio-impedance device was constructed through a series of iterative enhancements and improvements of existing BIA instrumentation. Key features of the design included an easy to construct current-source and compact PCB design. The final device was trialled with 22 human volunteers and measured impedance was compared against body composition estimates obtained by DEXA scan. This enabled the development of newer techniques to make BIA predictions. To add a ‘visual aspect’ to BIA, volunteers were scanned in 3D using an inexpensive scattered light gadget (Xbox Kinect controller) and 3D volumes of their limbs were compared with BIA measurements to further improve BIA predictions. A three-stage digital filtering scheme was also implemented to enable extraction of heart-rate data from recorded bio-electrical signals. Additionally modifications have been introduced to measure change in bio-impedance with motion, this could be adapted to further improve accuracy and veracity for limb composition analysis. The findings in this thesis aim to give new direction to the prediction of body composition using BIA. The design development and refinement applied to BIA in this research programme suggest new opportunities to enhance the accuracy and clinical utility of BIA for the prediction of body composition analysis. In particular, the use of bio-impedance to predict limb volumes which would provide an additional metric for body composition measurement and help distinguish between fat and muscle content.

Design of few-mode fibers with up to 12 modes and low differential mode delay

In this paper, we investigate the design of few-mode fibers (FMFs) guiding 4 to 12 non-degenerate linearly polarized (LP) modes with low differential mode delay (DMD) over the C-band, suitable for long-haul transmission. The refractive index profile considered is composed by a graded-core with a cladding trench (GCCT). The optimization of the profile parameters aims the lowest possible DMD and macro-bend losses (MBL) lower than the ITU-T standard recommendation. The optimization results show that the optimum DMD and the MBL scale with the number of modes. Additionally, it is shown that the refractive-index relative difference at the core center is one of the most preponderant parameters, allowing to reduce the DMD at the expense of increasing MBL. Finally, the optimum DMD obtained for 12 LP modes is lower than 3 ps/km. © 2014 IEEE.

Design of few-mode fibers with M-modes and low differential mode delay

In this paper, we investigate the design of few-mode fibers (FMFs) guiding 2 to 12 linearly polarized (LP) modes with low differential mode delay (DMD) over the C-band, suitable for long-haul transmission. Two different types of refractive index profile have been considered: a graded-core with a cladding trench (GCCT) profile and a multi-step-index (MSI) profile. The profiles parameters are optimized in order to achieve: the lowest possible DMD and macro-bend losses (MBL) lower than the ITU-T standard recommendation. The optimization results show that the MSI profiles present lower DMD than the minimum achieved with a GCCT profile. Moreover, it is shown that the optimum DMD and the MBL scale with the number of modes for both profiles. The optimum DMD obtained for 12 LP modes is lower than 3 ps/km using a GCCT profile and lower than 2.5 ps/km using a MSI profile. The optimization results reveal that the most preponderant parameter of the GCCT profile is the refractive index relative difference at the core center, Δnco. Reducing Δn co, the DMD is reduced at the expense of increasing the MBL. Regarding the MSI profiles, it is shown that 64 steps are required to obtain a DMD improvement considering 12 LP modes. Finally, the impact of the fabrication margins on the optimum DMD is analyzed. The probability of having a manufactured FMF with 12 LP modes and DMD lower than 12 ps/km is approximately 68% using a GCCT profile and 16% using a MSI profile. © 2013 IEEE.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Design rules for nonlinear spectral compression in optical fibers

We present comprehensive design rules to optimize the process of spectral compression arising from nonlinear pulse propagation in an optical fiber. Extensive numerical simulations are used to predict the performance characteristics of the process as well as to identify the optimal operational conditions within the space of system parameters. It is shown that the group velocity dispersion of the fiber is not detrimental and, in fact, helps achieve optimum compression. We also demonstrate that near-transform-limited rectangular and parabolic pulses can be generated in the region of optimum compression.

Practical design considerations of cascaded hybrid battery storage systems

The high cost of batteries has led to investigations in using second-life ex-transportation batteries for grid support applications. Vehicle manufacturers currently all have different specifications for battery chemistry, arrangement of cells, capacity and voltage. With anticipated new developments in battery chemistry which could also affect these parameters, there are, as yet, no standards defining parameters in second life applications. To overcome issues relating to sizing and to prevent future obsolescence for the rest of the energy storage system, a cascaded topology with an operating envelope design approach has been used to connect together modules. This topology offers advantages in terms of system reliability. The design methodology is validated through a set of experimental results resulting in the creation of surface maps looking at the operation of the converter (efficiency and inductor ripple current). The use of a pre-defined module operating envelope also offers advantages for developing new operational strategies for systems with both hybrid battery energy systems and also hybrid systems including other energy sources such as solar power.

Uniform design for the optimization of Al2O3 nanofilms produced by electrophoretic deposition

Surface modification by means of nanostructures is of interest to enhance boiling heat transfer in various applications including the organic Rankine cycle (ORC). With the goal of obtaining rough and dense aluminum oxide (Al2O3) nanofilms, the optimal combination of process parameters for electrophoretic deposition (EPD) based on the uniform design (UD) method is explored in this paper. The detailed procedures for the EPD process and UD method are presented. Four main influencing conditions controlling the EPD process were identified as nanofluid concentration, deposition time, applied voltage and suspension pH. A series of tests were carried out based on the UD experimental design. A regression model and statistical analysis were applied to the results. Sensitivity analyses of the effect of the four main parameters on the roughness and deposited mass of Al2O3 films were also carried out. The results showed that Al2O3 nanofilms were deposited compactly and uniformly on the substrate. Within the range of the experiments, the preferred combination of process parameters was determined to be nanofluid concentration of 2 wt.%, deposition time of 15 min, applied voltage of 23 V and suspension pH of 3, yielding roughness and deposited mass of 520.9 nm and 161.6 × 10− 4 g/cm2, respectively. A verification experiment was carried out at these conditions and gave values of roughness and deposited mass within 8% error of the expected ones as determined from the UD approach. It is concluded that uniform design is useful for the optimization of electrophoretic deposition requiring only 7 tests compared to 49 using the orthogonal design method.

The ageing ocular surface:challenges for biomaterials design and function

Changing demographics and in particular an increasingly ageing population, in combination with improved longevity, will have a major impact on changing the face of human diseases and likewise the demand for appropriate biomaterials. The ocular surface is a multifaceted system that combines to create a unique mucosal surface, which includes the cornea, conjunctiva, sclera and lids of the eye. Physical parameters such as the eyelids and eyelashes, combined with the numerous secretory glands that produce the complex tear film, act together to protect and maintain the cornea. Unfortunately an ageing tear film and lacrimal functional unit can lead to impairment of this magnificently orchestrated structure. No single mechanism or modification is responsible but, whatever the cause, the consequence is a reduction in tear stability. An uncompromised tear film is fundamental to a healthy ocular surface. In the face of progressively changing demographics and consequent requirements for medical intervention and medical device developments, it is important to understand what effects the ageing process has on these anterior ocular structures.