The potential of electron beam irradiation for simultaneous surface modification and bioresorption control of PLLA for medical device applications

Bioresorbable polymers have been widely investigated as materials exhibiting significant potential for successful application in the medical fields of bone fixation devices and drug delivery. Further to the ability to control degradation, surface engineering of polymers has been highlighted as a key method central to their development. Previous work has demonstrated the ability of electron beam (e-beam) technology to control the degradation profiles and bioresorption of a number of commercially relevant bioresorbable polymers (poly-l-lactic acid (PLLA), L-lactide/ DL-lactide co-polymer (PLDL) and poly(lactic-co-glycolic acid) (PLGA). This work investigates the further potential of e-beam technology to impart added biofunctionality through the manipulation of polymer (PLLA) surface properties. A Dynamatron Continuous DC e-beam unit (Synergy Health, UK), with beam energies of 0.5, 0.75, and 1.5 MeV, was used for the irradiation of PLLA samples with delivered surface doses of 150 or 500 kGy at each energy level. The chosen conditions reflect the need to achieve a specific surface modification for the control of surface degradation as demonstrated in previous work. Surface characterization was then performed using contact angle analysis, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy.
Results demonstrated a significant increase in surface wettability post e-beam treatment. In correlation with this, XPS data showed the introduction of oxygen-containing functional groups to the surface of PLLA. Raman spectroscopy indicated chain scission in the near surface region of PLLA. E-beam irradiation did not seem to affect the surface roughness of PLLA as a direct consequence of the treatment. In conclusion electron beam surface modification has been found to modify both the surface-to-bulk bioresorption profile and the surface hydrophilicity. Both could provide benefits in relation to the performance of implantable medical devices.

Improving antimicrobial release kinetics from hydrophobic polymer implants via ion pairing to combat biomedical-device related infection

Purpose The aim of this study is to improve the drug release properties of antimicrobial agents from hydrophobic biomaterials using using an ion pairing strategy. In so doing antimicrobial agents may be eluted and maintained over a sufficient time period thereby preventing bacterial colonisation and subsequent biofilm formation on medical devices. Methods The model antimicrobial agent was chlorhexidine and the selected fatty acid counter ions were capric acid, myristic acid and stearic acid. The polymethyl methacrylate films were loaded with 2% of fatty acid:antimicrobial agent at the following molar ratios; 0.5:1M, 1:1M and 2:1M and thermally polymerized using azobisisobutyronitrile initiator. Drug release experiments were subsequently performed over a 3-month period and the mass of drug released under sink conditions (pH 7.0, 37oC) quantified using a validated HPLC-UV method. Results In all platforms, a burst of chlorhexidine release was observed over the initial 24-hour period. Similar release kinetics were observed between the formulations during the initial 28 days. However, as time progressed, the chlorhexidine baseline plateaued after 56 days whereas formulations containing the counterions appeared to continuously elute linearly with time. As can be observed in figure 1, the rank order of total chlorhexidine release in the presence of 0.5M fatty acid was myristic acid (40%) > capric acid (35%) > stearic acid (30%)> chlorhexidine baseline (15%). Conclusion The incorporation of fatty acids within the formulation significantly improved chlorhexidine solubility within both the monomer and the polymer and enhanced the drug release kinetics over the period of study. This is attributed to the greater diffusivity of chlorhexidine through PMMA in the presence of fatty acids. In th absence of fatty acids, chlorhexidine release was facilitated by dissolution of surface associated drug particles. This study has illustrated the ability of fatty acids to modulate chlorhexidine release from a model biomaterial through enhanced diffusivity. This strategy may prove advantageous for improved medical devices with enhanced resistance to infection.

Channel Measurements of Device-to-Device Communications at 2.45 GHz

In the future, device-to-device communications will become a fundamental part of cellular communications. Interoperability between handsets will be facilitated using frequencies located in a number of bands including those found in the Industrial, Scientific and Medical (ISM) band at 2.45 GHz. In this paper, we present the results of channel measurements made between two hypothetical cellular handsets operating at 2.45 GHz in an outdoor environment. We consider a range of typical usage scenarios such as both user equipment being held at the head while imitating a voice call, placed in user's pocket for both stationary and dynamic links. A range of parameter estimates obtained using the shadowed κ-μ fading model are also presented.

Fibre laser joining of highly dissimilar materials: Commercially pure Ti and PET hybrid joint for medical device applications

Laser transmission joining (LTJ) is growing in importance, and has the potential to become a niche technique for the fabrication of hybrid plastic-metal joints for medical device applications. The possibility of directly joining plastics to metals by LTJ has been demonstrated by a number of recent studies. However, a reliable and quantitative method for defining the contact area between the plastic and metal, facilitating calculation of the mechanical shear stress of the hybrid joints, is still lacking. A new method, based on image analysis using ImageJ, is proposed here to quantify the contact area at the joint interface. The effect of discolouration on the mechanical performance of the hybrid joints is also reported for the first time. Biocompatible polyethylene terephthalate (PET) and commercially pure titanium (Ti) were selected as materials for laser joining using a 200 W CW fibre laser system. The effect of laser power, scanning speed and stand-off distance between the nozzle tip and top surface of the plastic were studied and analysed by Taguchi L9 orthogonal array and ANOVA respectively. The surface morphology, structure and elemental composition on the PET and Ti surfaces after shearing/peeling apart were characterized by SEM, EDX, XRD and XPS.

Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device

Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies.

Laser-fabricated PET-Ti Hybrid Joints for Medical Device Applications

Currently, micro-joining of plastic parts to metal parts in medical devices is achieved by using medical adhesives, For example, pacemakers, defibrillators and neurological stimulators are designed using silicone adhesive to seal the joint between the polyurethane connector module and the titanium can [1]. Nevertheless, the use of adhesive is problematic because it requires a long time to cure and has high tendency to produce leachable products which might be harmful to the human body. An alternative for directly joining plastics to metal without adhesive is therefore required. Laser transmission joining (LTJ) is growing in importance, and has the potential to gain the niche in micro-fabrication of plastics-metal hybrid joints for medical device applications. The possibility of directly joining plastics to metal by LTJ technique have been demonstrated by a number of studies in recent literature [2]. The widely-accepted understanding of LTJ between plastics and metal is that generation and rapid expansion of micro-bubbles at the plastics-metal interface exert high local pressure to press the melted plastics towards the metal surface features during the laser processing [2]. This subsequently creates the plastics-metal hybrid joint by the mechanisms of mechanical interlocking as well as chemical and physical bonds between the plastics and metal surfaces. Although the micro-bubbles can help promote the mechanical interlocking effect to increase the joint strength, the creation of bubble is a random and complex process depending on the complicated interactions between the laser intensity, thermal degradation properties of plastics, surface temperature and topographical features of metal. In an ideal situation, it is desirable to create the hybrid plastics-metal joint without bubbles. However, the mechanical performance of the hybrid plastics-metal joint without bubbles is still unknown, and systematic comparison between the hybrid joints with and without bubbles is lacking in literature. This becomes the objective of this study. In this work, the laser process parameters were carefully chosen from a preliminary study, such that different hybrid joints: with and without bubbles can be produced and compared. Biocompatible PET and commercially pure Ti were selected as materials for laser joining.

Photonic devices for optical and RF signal processing

O presente trabalho tem por objectivo o estudo de novos dispositivos fotónicos aplicados a sistemas de comunicações por fibra óptica e a sistemas de processamento de sinais RF. Os dispositivos apresentados baseiam-se em processamento de sinal linear e não linear. Dispositivos lineares ópticos tais como o interferómetro de Mach-Zehnder permitem adicionar sinais ópticos com pesos fixos ou sintonizáveis. Desta forma, este dispositivo pode ser usado respectivamente como um filtro óptico em amplitude com duas saídas complementares, ou, como um filtro óptico de resposta de fase sintonizável. O primeiro princípio de operação serve como base para um novo sistema fotónico de medição em tempo real da frequência de um sinal RF. O segundo princípio de operação é explorado num novo sistema fotónico de direccionamento do campo eléctrico radiado por um agregado de antenas, e também num novo compensador sintonizável de dispersão cromática. O processamento de sinal é não linear quando sinais ópticos são atrasados e posteriormente misturados entre si, em vez de serem linearmente adicionados. Este princípio de operação está por detrás da mistura de um sinal eléctrico com um sinal óptico, que por sua vez é a base de um novo sistema fotónico de medição em tempo real da frequência de um sinal RF. A mistura de sinais ópticos em meios não lineares permite uma operação eficiente numa grande largura espectral. Tal operação é usada para realizar conversão de comprimento de onda sintonizável. Um sinal óptico com multiplexagem no domínio temporal de elevada largura de banda é misturado com duas bombas ópticas não moduladas com base em processos não lineares paramétricos num guia de ondas de niobato de lítio com inversão periódica da polarização dos domínios ferroeléctricos. Noutro trabalho, uma bomba pulsada em que cada pulso tem um comprimento de onda sintonizável serve como base a um novo conversor de sinal óptico com multiplexagem no domínio temporal para um sinal óptico com multiplexagem no comprimento de onda. A bomba é misturada com o sinal óptico de entrada através de um processo não linear paramétrico numa fibra óptica com parâmetro não linear elevado. Todos os dispositivos fotónicos de processamento de sinal linear ou não linear propostos são experimentalmente validados. São também modelados teoricamente ou através de simulação, com a excepção dos que envolvem mistura de sinais ópticos. Uma análise qualitativa é suficiente nestes últimos dispositivos.

SWORD: an intelligent vibratory wearable device to improve rehabilitation in stroke patients

Anualmente ocorrem cerca de 16 milhões AVCs em todo o mundo. Cerca de metade dos sobreviventes irá apresentar défice motor que necessitará de reabilitação na janela dos 3 aos 6 meses depois do AVC. Nos países desenvolvidos, é estimado que os custos com AVCs representem cerca de 0.27% do Produto Interno Bruto de cada País. Esta situação implica um enorme peso social e financeiro. Paradoxalmente a esta situação, é aceite na comunidade médica a necessidade de serviços de reabilitação motora mais intensivos e centrados no doente. Na revisão do estado da arte, demonstra-se o arquétipo que relaciona metodologias terapêuticas mais intensivas com uma mais proficiente reabilitação motora do doente. Revelam-se também as falhas nas soluções tecnológicas existentes que apresentam uma elevada complexidade e custo associado de aquisição e manutenção. Desta forma, a pergunta que suporta o trabalho de doutoramento seguido inquire a possibilidade de criar um novo dispositivo de simples utilização e de baixo custo, capaz de apoiar uma recuperação motora mais eficiente de um doente após AVC, aliando intensidade com determinação da correcção dos movimentos realizados relativamente aos prescritos. Propondo o uso do estímulo vibratório como uma ferramenta proprioceptiva de intervenção terapêutica a usar no novo dispositivo, demonstra-se a tolerabilidade a este tipo de estímulos através do teste duma primeira versão do sistema apenas com a componente de estimulação num primeiro grupo de 5 doentes. Esta fase validará o subsequente desenvolvimento do sistema SWORD. Projectando o sistema SWORD como uma ferramenta complementar que integra as componentes de avaliação motora e intervenção proprioceptiva por estimulação, é descrito o desenvolvimento da componente de quantificação de movimento que o integra. São apresentadas as diversas soluções estudadas e o algoritmo que representa a implementação final baseada na fusão sensorial das medidas provenientes de três sensores: acelerómetro, giroscópio e magnetómetro. O teste ao sistema SWORD, quando comparado com o método de reabilitação tradicional, mostrou um ganho considerável de intensidade e qualidade na execução motora para 4 dos 5 doentes testados num segundo grupo experimental. É mostrada a versatilidade do sistema SWORD através do desenvolvimento do módulo de Tele-Reabilitação que complementa a componente de quantificação de movimento com uma interface gráfica de feedback e uma ferramenta de análise remota da evolução motora do doente. Finalmente, a partir da componente de quantificação de movimento, foi ainda desenvolvida uma versão para avaliação motora automatizada, implementada a partir da escala WMFT, que visa retirar o factor subjectivo da avaliação humana presente nas escalas de avaliação motora usadas em Neurologia. Esta versão do sistema foi testada num terceiro grupo experimental de cinco doentes.

Fuzzy rule extraction from input/output data

Several alternative approaches have been discussed: Levenberg-Marquardt - no satisfactory convergence speed + local minimum, Bacterial algorithm - problems with large dimensionality (speed), Clustering - no safe criterion for number of clusters + dimentionality problem.

Microextração adsortiva em barra (BAuE) : fundamentos avanços e aplicações na análise vestigial de compostos emergentes em matrizes reais

Tese de doutoramento, Química (Química Analítica), Universidade de Lisboa, Faculdade de Ciências, 2014

Enhancing extractive summarization with automatic post-processing

Tese de doutoramento, Informática (Ciência da Computação), Universidade de Lisboa, Faculdade de Ciências, 2015