Recent Trends in Applying Ortho-Nitrobenzyl Esters for the Design of Photo-Responsive Polymer Networks

Polymers with light-responsive groups have gained increased attention in the design of functional materials, as they allow changes in polymers properties, on demand, and simply by light exposure. For the synthesis of polymers and polymer networks with photolabile properties, the introduction o-nitrobenzyl alcohol (o-NB) derivatives as light-responsive chromophores has become a convenient and powerful route. Although o-NB groups were successfully exploited in numerous applications, this review pays particular attention to the studies in which they were included as photo-responsive moieties in thin polymer films and functional polymer coatings. The review is divided into four different sections according to the chemical structure of the polymer networks: (i) acrylate and methacrylate; (ii) thiol-click; (iii) epoxy; and (iv) polydimethylsiloxane. We conclude with an outlook of the present challenges and future perspectives of the versatile and unique features of o-NB chemistry

Development of a direct metalisation method for micro-engineering

This research concentrates on the establishment of a metalisation and micro-patterning technique that eliminates metal evaporation and/or photoresist molding procedures. The process design is chosen from the analysis of the broad field of direct metalisation techniques where novel photocatalysts or photoreducing agents are increasingly employed to create new processes. The new photolithographic process in this study introduces two novel photoreducing agents for additive metal thin film fabrication: methoxy poly(ethylene glycol) and photosystem I. This work proves the concept of using light energy to directly reduce metal ions incorporated within an ion-exchanged polyimide substrate to produce metal thin films. The patterning step can be operated at atmospheric pressure, in a dry environment, using a coating of the photoreducing agent. This process offers a significant improvement to prior related work that relied on a water layer to enable the metalisation. Of particular importance for this process is the influence of light energy dose and heat treatment, which promote silver nanoparticles growth at the cost of degradation of the substrate polymer. The investigation was carried out thoroughly by laser writing experiments for a selected range of laser power and scan speed. To complement the phenomenon observed in the laser experiments, prolonged UV light exposure time and heat treatment experiments were carried out to confirm the hypothesis postulated in this thesis. The morphology of the silver nanoparticles produced, the changes of the substrate surface and the adhesion of electroless plating were characterised. Results indicate that UV irradiation with the energy density required for reasonable production speed causes inevitable molecular damage to the polymer substrate. Photosystem I was found to be able to catalyse the production of visually similar silver thin film by light sources in the blue region. Using a similar light intensity, the exposure time was reduced by an order of magnitude whilst the degradation phenomenon observed during the UV process appears to be eradicated. With the fundamentals of the process established in this thesis, future optimization is suggested for the transition from a proof of concept to industrial implementation

Spatial Surface Functionalization Based on Photo-induced Thiol Reactions

Surface functionalization is important for modern science, technology as well as human¡¯s daily life. To endow different surfaces with various unique properties, lots of effort has been devoted to develop innovative chemical methods utilized for surface functionalization. Due to the controllability both spatially and temporally, photo-based functionalization is one of the most convenient surface modification methods. This doctoral thesis mainly focuses on photo-induced thiol chemistries for surface functionalization. In Chapter 1, an introduction is given to describe the recent progress in the field of surface patterning technologies as well as newly developed photo chemistries. In Chapter 2, a fast (<15 s), initiator-free and versatile surface photopatterning method based on UV-induced thiol-yne click chemistry for creating precise superhydrophobic-superhydrophilic micropatterns is introduced. The method is based on the formation and modification of alkyne-functionalized polymer surfaces with porous structure. This alkyne surface can be modified with variety of thiol-containing chemicals under UV irradiation without any photoinitiator, in different solvents and even in water rapidly. Superhydrophobic-superhydrophilic micropatterns with feature resolution down to 10 ¦Ìm could be created facilely on this polymer surface. Applications for the formation of microarrays of droplets as well as high-density microarrays of cells are also shown in the chapter. In Chapter 3, a simple, rapid and convenient surface functionalization method based on UV-induced thiol-ene click chemistry to create transparent and mechanically robust micropatterns on smooth glass or flexible polymer films is described. These patterns enable the fabrication of high-density arrays of low surface tension liquid microdroplets via discontinuous dewetting. A wide range of organic solvents including ethanol, acetone, DMF, dichloromethane and even hexane (surface tension 18.4 mN/m), could be used to produce such microdroplet arrays with complex shapes. This unique method provides an important solution for ultra high-throughput chemical screening applications. The possibility of parallel addition of different chemicals into the individual organic microdroplets is demonstrated. This approach is also employed to create high-density arrays of polymer microlenses with defined 3D shapes. In addition, this method is uniquely suited to create patterns of hydrophobic nanoparticles that can be only dispersed in organic solvents. In Chapter 4, a UV-induced 1,3-dipolar nucleophilic addition of tetrazoles to thiols is demonstrated. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV-induced tetrazole-thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer--polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site-selective surface functionalization. Superhydrophobic--hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole-functionalized porous polymer surface with hydrophobic and hydrophilic thiols. In addition, a biotin-functionalized surface could be fabricated in aqueous solutions under long-wavelength UV irradiation. In the last part of this thesis, a brief summarz and outlook are present

Investigation of light-addressable potentiometric sensors for electrochemical imaging based on different semiconductor substrates

PhDLight-addressable potentiometric sensors (LAPS) and scanning photo-induced impedance microscopy (SPIM) have been extensively applied as chemical sensors and biosensors. This thesis focuses on the investigation of LAPS and SPIM for electrochemical imaging based on two different semiconductor substrates, silicon on sapphire (SOS) and indium tin oxide (ITO) coated glass. Firstly, SOS substrates were modified with 1,8-nonadiyne self-assembled organic monolayers (SAMs), which served as the insulator. The resultant alkyne terminals provided a platform for the further functionalization of the sensor substrate with various chemicals and biomolecules by Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) ‘click’ reactions. The CuAAC reaction combined with microcontact printing (μCP) was successfully used to create chemical patterns on alkyne-terminated SOS substrates. The patterned monolayers were found to be contaminated with the copper catalyst used in the click reaction as visualized by LAPS and SPIM. Different strategies for avoiding copper contamination were tested. Only cleaning of the silicon surfaces with an ethylenediaminetetraacetic acid tetrasodium salt (EDTA) solution containing trifluoroacetic acid after the ‘click’ modification proved to be an effective method as confirmed by LAPS and SPIM results, which allowed, for the first time, the impedance of an organic monolayer to be imaged. Furthermore, the 1,8-nonadiyne modified SOS substrate was functionalized and patterned with an RGD containing peptide, which was used to improve the biocompatibility of the substrate and cell adhesion. By seeding cells on the peptide patterned sensor substrate, cell patterning was achieved. Single cell imaging using LAPS and SPIM was attempted on the RGD containing peptide modified SOS substrate Finally, an ITO coated glass substrate was used as a LAPS substrate for the first time. The photocurrent response, the pH response, LAPS and SPIM imaging and its lateral resolution using ITO coated glass without any modification were investigated. Importantly, single cell images were obtained with this ITO-based LAPS systemChina Scholarship Council and Queen Mary University of Londo

Uni-axial Stretching Generated Poly (E-caprolactone) Film for Human Vascular Tissue Engineering Application

Ph.DDOCTOR OF PHILOSOPH

DIRECT PATTERNING OF NATURE-INSPIRED SURFACES FOR BIOINTERFACIAL APPLICATIONS

There are three major challenges for the design of patterned surfaces for biointerfacial applications: (i) durability of antibacterial/antifouling mechanisms, (ii) mechanical durability, and (iii) lifetime of the master mold for mass production of patterned surfaces. In this dissertation, we describe our contribution for the development of each of these challenges. The bioinspired surface, Sharklet AFTM, has been shown to reduce bacterial attachment via a biocide-free structure-property relationship effectively. Unfortunately, the effectiveness of polymer-based sharkskin surfaces is challenged over the long term by both eventual bacteria accumulation and a lack of mechanical durability. To address these common modes of failure, hard, multifunctional, antifouling, and antibacterial shark-skin patterned surfaces were fabricated via a solvent-assisted imprint patterning technique. A UV-crosslinkable adhesive material was loaded with titanium dioxide (TiO2)nanoparticles (NPs) from which shark skin microstructures were imprinted on a polyethylene terephthalate substrate. Furthermore, hard, multifunctional, antifouling, and antibacterial shark skin patterned surfaces were fabricated using inks comprised of zirconium dioxide (ZrO2) NPs and TiO2 NPs. The ZrO2 NPs provide an extremely hard and durable matrix in the final structure, while the TiO2 NPs provide active antibacterial functionality in the presence of UV light via photooxidation. The dynamic water contact angle, mechanical, antibacterial, and antifouling characteristics of the shark skin patterned surfaces were investigated as a function of TiO2 content. We then demonstrated the multifunctional shark skin system’s suitability for use as an antifouling biosensor. Lastly, we described the design of a durable, hard master mold for pattern transfer. The lifetime of many of the current molds is limited by a lack of mechanical durability as well as cost. In this study, ZrO2 NPs were imprinted on a variety of substrates using a solvent-assisted patterning technique and subsequently annealed to increase the mechanical durability of the mold. Polymer replications were demonstrated using the hard ZrO2 mold with thermal and UV nanoimprinting lithography techniques, and injection molding. After up to 115,000 injection molding cycles, there was no delamination or breakage in the ZrO2 mold. The high hardness and durability, as demonstrated through the many replication cycles, suggests that the ZrO2 mold has excellent potential for use in the mass production of patterned polymer replicas. We also explored the nanopatterning of stainless steel using the ZrO2 mold. The solution-processability and simple patterning technique of ZrO2 NPs enable large-area and cost-effective fabrication of the hard molds which can be used for the variety of nano and micro-replication technologies

Application of advanced surface patterning techniques to study cellular behavior

Surface manipulation for the fabrication of chemical or topographic micro- and nanopatterns, has been central to the evolution of in vitro biology research. A high variety of surface patterning methods have been implemented in a wide spectrum of applications, including fundamental cell biology studies, development of diagnostic tools, biosensors and drug delivery systems, as well as implant design. Surface engineering has increased our understanding of cell functions such as cell adhesion and cell-cell interaction mechanics, cell proliferation, cell spreading and migration. From a plethora of existing surface engineering techniques, we use standard microcontact printing methods followed by click chemistry to study the role of intercellular contacts in collective cancer cell migration. Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). The spreading of these colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts. We find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that in cancer cell migration, cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration. Despite the remarkable progress in surface engineering technology and its applications, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photo-immobilization technique, comprising a light-dose dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable pattering step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes, and that our innovative approach has a great potential for further applications in cell science. In summary, this work introduces two novel and versatile paradigms of surface patterning for studying different aspects of cell behaviour in different cell types. The reliability of both setups is experimentally confirmed, providing new insight into the role of cell-cell contacts during collective cancer cell migration as well as the tip/stalk switch behaviour during angiogenesis

Light-addressable potentiometric sensors based on self-assembled organic monolayer modified silicon on sapphire substrates

PhDLight-addressable potentiometric sensors (LAPS) have become attractive in many chemical and biological sensor applications. This thesis introduces the use of self-assembled organic monolayers (SAMs) as the insulator in LAPS and scanning photo-induced impedance microscopy (SPIM) for the first time. Two types of monolayer assemblies with alkenes (1-octadecene or undecylenic acid) and alkynes (1, 8-nonadiyne) were immobilised on hydrogenated silicon on sapphire (SOS) or silicon through thermal hydrosilylation. Further derivations were performed on the 1, 8-nonadiyne monolayers via “click” reactions. The monolayers were characterised by water contact angle, ellipsometry and X-ray photoelectron spectroscopy (XPS). LAPS/SPIM measurements with SAM-modified SOS showed the same good spatial resolution that was previously obtained with a conventional SiO2 insulator on SOS, but also a significant improvement in the accuracy of LAPS and the sensitivity of SPIM. Surface potential imaging using LAPS insulated by SAMs was validated by studying micropatterns of poly(allylamine hydrochloride) (PAH), poly(styrene sulfonate) (PSS) and DNA on a PAH template. Two potential strategies for chemically patterning SAMs on oxide-free SOS or Si substrates were investigated and compared. Microcontact printing (μCP) followed by “click” chemistry is a mild and efficient means of modifying the surface, whereas the combination of photolithography and “click” chemistry is not. LAPS was also shown to be extremely sensitive to surface contamination. LAPS/SPIM insulated by SAMs can also generate impedance images with high resolution and high sensitivity. Microcapsules labelled with gold nanoparticles (AuNPs) integrated with a femtosecond laser were used for the validation. In contrast, capsules without AuNPs showed no SPIM response at all, indicating that the impregnation with AuNPs can significantly increase the impedance of microcapsules. Finally, new instrumentation to integrate two-photon fluorescence microscopy with LAPS/SPIM was proposed. Preliminary results have shown that the new technique is promising to produce two-dimensional electrochemical images and two-photon fluorescent images of the cell-attachment area with subcellular resolutionChina Scholarship Council Queen Mary University of London

Polymer-based device fabrication and applications using direct laser writing technology

Polymer materials exhibit unique properties in the fabrication of optical waveguide devices, electromagnetic devices, and bio-devices. Direct laser writing (DLW) technology is widely used for micro-structure fabrication due to its high processing precision, low cost, and no need for mask exposure. This paper reviews the latest research progresses of polymer-based micro/nano-devices fabricated using the DLW technique as well as their applications. In order to realize various device structures and functions, different manufacture parameters of DLW systems are adopted, which are also investigated in this work. The flexible use of the DLW process in various polymer-based microstructures, including optical, electronic, magnetic, and biomedical devices are reviewed together with their applications. In addition, polymer materials which are developed with unique properties for the use of DLW technology are also discussed