Novel multifunctional materials based on ionic liquids: on demand micro-valve actuation for lab-on-a-chip applications

We present the fabrication, characterization and performance as a micro-valve of four novel materials, ionogels, consisting in a polymeric structure with benzospiro-pyran units and phosphonium based ionic liquids. Each inonogel is photopolymerised in the channels of a poly(methyl methacrylate) microfluidic device generating four different micro-valves. The micro-valves are actuated by simply applying local white light irradiation and each of the micro-valves opens specifically at one particular time. Therefore, flows can be independently controlled by one single light source while the synthesis of ionogels with different ionic liquids enables distinct valve ac-tuation. Moreover, the microfluidic device can be reusable many times

Ionogel-based light-actuated valves for controlling liquid flow in micro-fluidic manifolds

We present the fabrication, characterisation and performance of four novel ionic liquid polymer gels (ionogels) as photo-actuated valves incorporated into micro-fluidic manifolds. The ionogels incorporate benzospiropyran units and phosphonium-based ionic liquids. Each ionogel is photo-polymerised in situ in the channels of a poly(methyl methacrylate) micro-fluidic device, generating a manifold incorporating four different micro-valves. The valves are actuated by simply applying localised white light irradiation, meaning that no physical contact between the actuation impulse (light) and the valve structure is required. Through variation of the composition of the ionogels, each of the micro-valves can be tuned to open at different times under similar illumination conditions. Therefore, flows through the manifold can be independently controlled by a single light source. At present, the contraction process to open the channel is relatively rapid (seconds) while the recovery (expansion) process to re-close the channel is relatively slow (minutes), meaning that the valve, in its current form, is better suited for single-actuation events

Peptide-Polymer Conjugates for Therapeutic Applications

Over the last ten years the attention of the pharmaceutical industry has shifted away from small molecules to focus on new biologics such as antibodies, proteins and therapeutic peptides. Herein, peptides have emerged as a particularly interesting category that fills a niche between small molecule chemicals and the larger proteins. Although they have great potential for drug development, their use is still limited due to their intrinsic low systemic stability, rapid renal elimination and poor membrane permeability. Various formulations have been developed to take advantage of their therapeutic properties, one of the most promising strategies being chemical conjugation to a polymer. Peptide-polymer conjugates are hybrid materials that consist of one or more synthetic polymers covalently attached to one or more peptide fragments. The aim of this thesis was to provide an insight into the requirements for the design of peptide-polymer conjugates for therapy. Chapter 1 illustrates the state of the art in the development of peptides for therapeutic applications, exemplifies the different architectures and structures of peptide-polymer conjugates and discusses ongoing efforts to improve and diversify the range and applications of these conjugates. Chapter 2 describes a novel synthetic strategy to prepare PHPMA based peptide-polymer conjugates via thiol chemistry starting from poly(pentafluorophenyl methacrylate). By varying the feed composition, the extent of side chain modification could be controlled. Further modification of the reactive copolymer scaffolds led to the site specific attachment of model peptides. This method was used to synthesize stable as well as pH and redox sensitive peptide-polymer conjugates and the release of the peptide from the polymer backbone was studied in acidic and redox conditions. In Chapter 3, the aim was to construct a peptide-polymer conjugate that could serve to promote intracellular delivery and drug release but also play a role in the intracellular trafficking of the drug. To this end, coiled coil peptides E3/K3 was attached to a PHPMA polymer backbone and was used to facilitate release from the backbone at acidic pH and further endosomal escape. Initially, the membrane lytic properties of E3/K3 and three newly designed E3/K3X motifs on model membranes were investigated as a function of pH. Secondly, the potential application of E3/K3 peptide-polymer conjugate for cytoplasmic delivery was evaluated in vitro. Chapter 4 explores the synthesis and in vitro therapeutic activity of synthetic peptide-polymer conjugates focusing on the inhibition of an oncogenic transcription factor (AP-1). To this end, AFosW peptide, a peptide binder that can interfere with AP-1 formation was attached to a polymer backbone via a redox or pH sensitive linker using a strategy developed in Chapter 2. Fluorescent microscopy and flow cytometry provided an insight into the cellular uptake of these conjugates. Their ability to interfere with AP-1 formation in vitro was quantified. Chapter 5 describes the synthesis of a second generation of peptide-polymer conjugates for AP-1 inhibition that along the FosW dominant negative peptide also incorporates a motif that facilitates endosomal escape and a nuclear localization sequence. To investigate the potential application for therapy, the conjugates were evaluated and compared with regard to their ability to inhibit AP-1 formation in living cells

Effect of RF Power on the Physical Properties of Sputtered ZnSe Nanostructured Thin Films for Photovoltaic Applications

Zinc selenide (ZnSe) thin films were deposited by RF magnetron sputtering in specific conditions, onto optical glass substrates, at different RF plasma power. The prepared ZnSe layers were afterwards subjected to a series of structural, morphological, optical and electrical characterizations. The obtained results pointed out the optimal sputtering conditions to obtain ZnSe films of excellent quality, especially in terms of better optical properties, lower superficial roughness, reduced micro-strain and a band gap value closer to the one reported for the ZnSe bulk semiconducting material. Electrical characterization were afterwards carried out by measuring the current–voltage (I-V) characteristics at room temperature, of prepared “sandwich”-like Au/ZnSe/Au structures. The analysis of I-V characteristics have shown that at low injection levels there is an Ohmic conduction, followed at high injection levels, after a well-defined transition voltage, by a Space Charge Limited Current (SCLC) in the presence of an exponential trap distribution in the band gap of the ZnSe thin films. The results obtained from all the characterization techniques presented, demonstrated thus the potential of ZnSe thin films sputtered under optimized RF plasma conditions, to be used as alternative environmentally-friendly Cd-free window layers within photovoltaic cells manufacturing