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.

Anterior ophthalmic imaging

Improvements in imaging chips and computer processing power have brought major advances in imaging of the anterior eye. Digitally captured images can be visualised immediately and can be stored and retrieved easily. Anterior ocular imaging techniques using slitlamp biomicroscopy, corneal topography, confocal microscopy, optical coherence tomography (OCT), ultrasonic biomicroscopy, computerised tomography (CT) and magnetic resonance imaging (MRI) are reviewed. Conventional photographic imaging can be used to quantify corneal topography, corneal thickness and transparency, anterior chamber depth and lateral angle and crystalline lens position, curvature, thickness and transparency. Additionally, the effects of tumours, foreign bodies and trauma can be localised, the corneal layers can be examined and the tear film thickness assessed. © 2006 The Authors.

Microchannels in conventional single-mode fibers

Microchannels are fabricated into conventional single-mode fibers by femtosecond laser processing and chemical etching. Fabrication limitations imposed by the fiber geometry are highlighted and resolved through a simple technique without compromising fabrication flexibility. A microfluidic fiber device consisting of a 4 μm wide microchannel that intersects the fiber core for refractive index sensing is further demonstrated. © 2006 Optical Society of America.

Magnetite-doped polydimethylsiloxane (PDMS) for phosphopeptide enrichment

Reversible phosphorylation plays a key role in numerous biological processes. Mass spectrometry-based approaches are commonly used to analyze protein phosphorylation, but such analysis is challenging, largely due to the low phosphorylation stoichiometry. Hence, a number of phosphopeptide enrichment strategies have been developed, including metal oxide affinity chromatography (MOAC). Here, we describe a new material for performing MOAC that employs a magnetite-doped polydimethylsiloxane (PDMS), that is suitable for the creation of microwell array and microfluidic systems to enable low volume, high throughput analysis. Incubation time and sample loading were explored and optimized and demonstrate that the embedded magnetite is able to enrich phosphopeptides. This substrate-based approach is rapid, straightforward and suitable for simultaneously performing multiple, low volume enrichments. © the Partner Organisations 2014.

SE(R)RS devices fabricated by a laser electrodispersion method

A novel laser electrodispersion (LE) technique was employed to deposit gold nanoparticles onto Si and SiOx surfaces. The LE technique combines laser ablation with cascade fission of liquid metal micro-drops, which results in the formation of nanoparticles upon rapid cooling. The shape and the size distribution of the Au nanoparticles prepared by LE depend on the nature of the support. Gold nanoparticles were also deposited in the channels of microreactors fabricated by wet etching of Si and used as SE(R)RS sensors. The influence of the nanoparticle surface density as well as of the nature of the substrate on the Raman response was studied. At an appropriate surface density of the deposited nanoparticles a significant enhancement of Raman signal was observed showing the possibility to create efficient SERS substrates. Application of microfluidic devices in surface enhanced Raman spectroscopy (SERS) in continuous-flow mode with sensor regeneration is described. © 2011 The Royal Society of Chemistry.

Structural and chemical modifications of typical South African biomasses during torrefaction

Torrefaction experiments were carried out for three typical South African biomass samples (softwood chips, hardwood chips and sweet sorghum bagasse) to a weight loss of 30wt.%. During torrefaction, moisture, non-structural carbohydrates and hemicelluloses were reduced, resulting in a structurally modified torrefaction product. There was a reduction in the average crystalline diameter (La) (XRD), an increase in the aromatic fraction and a reduction in aliphatics (substituted and unsubstituted) (CPMAS 13C NMR). The decrease in the aliphatic components of the lignocellulosic material under the torrefaction conditions also resulted in a slight ordering of the carbon lattice. The degradation of hemicelluloses and non-structural carbohydrates increased the inclusive surface area of sweet sorghum bagasse, while it did not change significantly for the woody biomasses.

Advances in characterisation, calibration and data processing speed of optical coherence tomography systems

This thesis describes advances in the characterisation, calibration and data processing of optical coherence tomography (OCT) systems. Femtosecond (fs) laser inscription was used for producing OCT-phantoms. Transparent materials are generally inert to infra-red radiations, but with fs lasers material modification occurs via non-linear processes when the highly focused light source interacts with the materials. This modification is confined to the focal volume and is highly reproducible. In order to select the best inscription parameters, combination of different inscription parameters were tested, using three fs laser systems, with different operating properties, on a variety of materials. This facilitated the understanding of the key characteristics of the produced structures with the aim of producing viable OCT-phantoms. Finally, OCT-phantoms were successfully designed and fabricated in fused silica. The use of these phantoms to characterise many properties (resolution, distortion, sensitivity decay, scan linearity) of an OCT system was demonstrated. Quantitative methods were developed to support the characterisation of an OCT system collecting images from phantoms and also to improve the quality of the OCT images. Characterisation methods include the measurement of the spatially variant resolution (point spread function (PSF) and modulation transfer function (MTF)), sensitivity and distortion. Processing of OCT data is a computer intensive process. Standard central processing unit (CPU) based processing might take several minutes to a few hours to process acquired data, thus data processing is a significant bottleneck. An alternative choice is to use expensive hardware-based processing such as field programmable gate arrays (FPGAs). However, recently graphics processing unit (GPU) based data processing methods have been developed to minimize this data processing and rendering time. These processing techniques include standard-processing methods which includes a set of algorithms to process the raw data (interference) obtained by the detector and generate A-scans. The work presented here describes accelerated data processing and post processing techniques for OCT systems. The GPU based processing developed, during the PhD, was later implemented into a custom built Fourier domain optical coherence tomography (FD-OCT) system. This system currently processes and renders data in real time. Processing throughput of this system is currently limited by the camera capture rate. OCTphantoms have been heavily used for the qualitative characterization and adjustment/ fine tuning of the operating conditions of OCT system. Currently, investigations are under way to characterize OCT systems using our phantoms. The work presented in this thesis demonstrate several novel techniques of fabricating OCT-phantoms and accelerating OCT data processing using GPUs. In the process of developing phantoms and quantitative methods, a thorough understanding and practical knowledge of OCT and fs laser processing systems was developed. This understanding leads to several novel pieces of research that are not only relevant to OCT but have broader importance. For example, extensive understanding of the properties of fs inscribed structures will be useful in other photonic application such as making of phase mask, wave guides and microfluidic channels. Acceleration of data processing with GPUs is also useful in other fields.

Precision emulsification for droplet and capsule production

Emulsions and microcapsules are typical structures in various dispersion formulations for pharmaceutical, food, personal and house care applications. Precise control over size and size distribution of emulsion droplets and microcapsules are important for effective use and delivery of active components and better product quality. Many emulsification technologies have been developed to meet different formulation and processing requirements. Among them, membrane and microfluidic emulsification as emerging technologies have the feature of being able to precisely manufacture droplets in a drop-by-drop manner to give subscribed sizes and size distributions with lower energy consumption. This paper reviews fundamental sciences and engineering aspects of emulsification, membrane and microfluidic emulsification technologies and their use for precision manufacture of emulsions for intensified processing. Generic application examples are given for single and double emulsions and microcapsules with different structure features. © 2013 The Society of Powder Technology Japan. Published by Elsevier B.V.

Slow light optofluidics:a proposal

The resonant slow light structures created along a thin-walled optical capillary by nanoscale deformation of its surface can perform comprehensive simultaneous detection and manipulation of microfluidic components. This concept is illustrated with a model of a 0.5 mm long, 5 nm high, triangular bottle resonator created at a 50 μm radius silica capillary containing floating microparticles. The developed theory shows that the microparticle positions can be determined from the bottle resonator spectrum. In addition, the microparticles can be driven and simultaneously positioned at predetermined locations by the localized electromagnetic field created by the optimized superposition of eigenstates of this resonator, thus exhibiting a multicomponent, near-field optical tweezer.

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.

A compact, portable and low cost generic interrogation strain sensor system using an embedded VCSEL, detector and fibre Bragg grating

We present a compact, portable and low cost generic interrogation strain sensor system using a fibre Bragg grating configured in transmission mode with a vertical-cavity surface-emitting laser (VCSEL) light source and a GaAs photodetector embedded in a polymer skin. The photocurrent value is read and stored by a microcontroller. In addition, the photocurrent data is sent via Bluetooth to a computer or tablet device that can present the live data in a real time graph. With a matched grating and VCSEL, the system is able to automatically scan and lock the VCSEL to the most sensitive edge of the grating. Commercially available VCSEL and photodetector chips are thinned down to 20 µm and integrated in an ultra-thin flexible optical foil using several thin film deposition steps. A dedicated micro mirror plug is fabricated to couple the driving optoelectronics to the fibre sensors. The resulting optoelectronic package can be embedded in a thin, planar sensing sheet and the host material for this sheet is a flexible and stretchable polymer. The result is a fully embedded fibre sensing system - a photonic skin. Further investigations are currently being carried out to determine the stability and robustness of the embedded optoelectronic components. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Modeling of Cylindrical Couette Flow of Rarefied Gas Between Rotating Cylinders

Петър Господинов, Добри Данков, Владимир Русинов, Стефан Стефанов - Изследвано е цилиндрично течение на Кует за разреден газ между два въртящи се цилиндъра. Получени са профилите на налягането, скоростта и температурата по метода на прякото статистическо моделиране (DSMC) и чрез числено решаване на уравненията на Навие-Стокс за свиваем флуид. Резултатите сочат много добро съвпадение за малки числа на Кнудсен Kn = 0.02. Показано е, че при различни кинематични гранични условия, газът изостава или избързва спрямо скоростта на стената, или има поведение на твърдо еластично тяло. Получените резултати са важни при решаването на неравнинни, задачи от микрофлуидиката с отчитане на ефектите на кривината.

Comparative Analysis of the Opposite Rotating Cylinders Impact over Couette Flow for Rarefied Gas

Петър Господинов, Добри Данков, Владимир Русинов, Стефан Стефанов - Иследвано е цилиндрично течение на Кует на разреден газ в случая на въртене на два коаксиални цилиндъра с еднакви по големина скорости, но в различни посоки. Целта на изследването е да се установи влиянието на малки скорости на въртене върху макрохарактеристиките – ρ, V , . Числените резултати са получени чрез използване на DSMC и числено решение на уравненията на Навие-Стокс за относително малки (дозвукови) скорости на въртене. Установено е добро съвпадение на резултатите получени по двата метода за Kn = 0.02. Установено е, че съществува “стационарна” точка за плътността и скоростта. Получените резултати са важни при решаването на неравнини, задачи от микрофлуидиката с отчитане на ефектите на кривината. Ключови думи: Механика на флуидите, Кинетична теория, Разреден газ, DSMC

Couette Gas Flow Between Cylinders with Different Temperature

Петър Господинов, Добри Данков, Владимир Русинов, Стефан Стефанов - Изследвано е стационарно течение на Кует на разреден газ в случая на въртене на вътрешния цилиндър и неподвижен външен цилиндър чрез използване на DSMC метод и числено решение на уравненията на Навие–Стокс за относително малка (дозвукова) скорост на въртене. Изследвани са различни случаи при промяна на температурата на въртящият се цилиндър и числото на Кнудсен. Целта на изследването е да се установи влиянието на малки скорости на въртене върху макрохарактеристиките – плътността, скоростта и температурата на газа. Установено е добро съвпадение на резултатите получени по двата метода за Kn = 0.02. Получените резултати са важни при решаването на неравнинни, задачи от микрофлуидиката с отчитане на ефектите на кривината. Ключови думи: механика на флуидите, кинетична теория, разреден газ, DSMC.

Artificial neural networks for surface roughness prediction when face milling Al 7075-T7351

In this work, different artificial neural networks (ANN) are developed for the prediction of surface roughness (R a) values in Al alloy 7075-T7351 after face milling machining process. The radial base (RBNN), feed forward (FFNN), and generalized regression (GRNN) networks were selected, and the data used for training these networks were derived from experiments conducted using a high-speed milling machine. The Taguchi design of experiment was applied to reduce the time and cost of the experiments. From this study, the performance of each ANN used in this research was measured with the mean square error percentage and it was observed that FFNN achieved the best results. Also the Pearson correlation coefficient was calculated to analyze the correlation between the five inputs (cutting speed, feed per tooth, axial depth of cut, chip°s width, and chip°s thickness) selected for the network with the selected output (surface roughness). Results showed a strong correlation between the chip thickness and the surface roughness followed by the cutting speed. © ASM International.