Browsing by Author "Ge, Yi"

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    Improvements in electrochemical glucose biosensors
    (Cranfield University, 2010-09) Fragkou, Vasiliki; Ge, Yi; Piletsky, Sergey A.; Turner, Anthony P. F.
    Diabetes is one of the leading causes of death and disability in the world. Even though insulin was discovered in 1920, an intense research on diabetes has been conducted during the last five decades and this is because of the market size. The huge demand is creating the need for the development of new approaches. This project involved the research aimed at better understanding and improvements in performance of glucose biosensors. In general, high surface area electrodes are desired as the high surface area provides more active sites for electrochemical reactions, and hence higher kinetic rate capability. Therefore, the determination of the active electrochemical surface area of the electrode is very important. A study has been conducted to determine the real electrochemical surface area of the Pelikan screen printed electrodes (SPEs) and a method has been optimised and established by Pelikan for the evaluation of their SPEs. Another very important issue that most of the current blood glucose monitoring tests are facing is the haematocrit effect, since the haematocrit differences observed in the blood samples can significantly affect glucose measurements. Therefore a study has been conducted in order to observe the absorption of the blood samples into the working electrode paste according to the haematocrit level. The second part of the study included the characterisation of the novel conjugated polymer made of N-(N, N’ diethyldicarbamoyl ethyl amido ethyl) aniline (NDDEAEA), the optimization of the conditions for the electrochemical polymerization, their application in grafting and finally the development of NDDEAEA based glucose biosensor. The new conducting polymer, acted as a matrix for the biosensor fabrication in this study, possesses macroiniferter properties and is capable of initiation free radical initiated addition polymerisation after formation of the polyaniline (PANI) material while preserving or even enhancing some of the PANI’s electrochemical properties. This material can potentially be used in the construction of novel Pelikan electrodes with enhanced integration functionalities, e.g. grafting non adhesive polymer coatings to assure that the poor performance in sensors as a result of impact of blood components can be mitigated. The final study included the development and optimisation of the reaction conditions for grafting a hyperbranched polymer onto the surface of the multi walled carbon nanotubes (MWCNT), using the A3 and B2 approach (described below). The aim of this work was achieving further increase in the sensitivity of Pelikan sensors.
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    Nanofunctionalised orthopaedic implants
    (2018-01) Mirza, Farhan A.; Ge, Yi
    Due to an aging population and younger patients presenting with musculoskeletal disorders, there is a need for orthopaedic implants with improved healing rates and longer implant life. Numerous research has developed implant surfaces with micro-topography and biomolecules to imitate the native extra cellular matrix (also known as biomimetic surfaces). This research has utilised such a biomimetic approach by immobilising the cell adhesive peptide, RGD (Arginine-Glycine-Aspartic Acid), to a titanium alloy Ti6Al4V surface. This research polymerised Hyperbranched Polyglycerol (HBPG) from the titanium surface using Ring Opening Multi-Branching Polymerisation (ROMBP). HBPG is a biologically compatible and non-toxic synthetic biopolymer, able to reduce non-specific protein adsorption, increase the titanium surface wetting (hydrophilicity), thereby limiting foreign body reactions. Extensive hydroxyl groups at the periphery of HBPG provides conjugation sites for biomolecule attachment. In this work the RGD peptide was conjugated to the polymer via a siloxane layer. This research developed a novel passivation solution for the preparation of the titanium alloy surface, using a mixture of hydrogen peroxide and nitric acid (a passivation mixture not used in the literature). This novel mixture was shown to etch the titanium surface, producing micro and nano surface features, both of which have been shown to improve cellular function in the literature. The hydrogen peroxide/nitric acid solution showed extensive oxidising ability on titanium, leading to the formation of reactable hydroxyl groups. Contact-angle measurements showed that the novel passivating solution produces a hydrophilic surface similar to that of peroxidation for 12-hours, but achieved in only 2-hours. In conjunction with the etching and oxidising abilities of hydrogen peroxide, the nitric acid reacts with the titanium surface, leading to the formation of a protective titanium oxide layer, enhancing corrosion resistance and improving biocompatibility. Biological investigations with the pre-osteoblast cell line MC3T3-E1 showed greater osteoblast cell attachment and adhesion strength, as well as improved bone matrix mineralisation on the passivated titanium surface functionalised with HBPG and the RGD peptide, compared to the raw and passivated titanium surfaces. Antibacterial testing of HBPG revealed substantially reduced bacterial cell colonies on the passivated/polymerised titanium surface, possibly arising from electrostatic and hydrophobic repulsion. This research has successfully developed a new titanium passivation solution (hydrogen peroxide/nitric acid) that can yield a contact-angle of around 35° in just 2-hours, rivalling the Piranha solution. The successful immobilisation of a cyclic RGD (cyclic-RGDfc) to a titanium surface functionalised with HBPG, has been shown in this research to drastically improve mineralised bone matrix production from the MC3T3-E1 cell line. This indicates earlier osseointegration of the implant may be possible, thereby improving patient healing times.
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    Studies of PLGA Nanoparticles for Pharmaceutical Applications
    (Cranfield University, 2014-08) Sun, Yanqi; Ge, Yi
    PLGA have already been successfully applied for controlled drug delivery systems by the pharmaceutical industry due to its biocompatibility, biodegradability and ease of processing. It has recently further been developed and formulated into a form of nanoparticle. The single emulsion evaporation method was used to prepare nanoparticles in this study. By varying different parameters such as the concentration of regents, the type of surfactant and emulsion method, different particle sizes and size distribution of PLGA nanoparticles could be obtained. The stability of PLGA nanoparticles was further investigated by assessing their thermal property over a certain period of time using DSC. The decrease of Tg confirmed the hydration and degradation of PLGA polymers and nanoparticles. The changes of surface morphology showed that the nanoparticles were in spherical shape and maintained smooth surface before the storage, whereas they started to lose their original shapes as well as agglomerate to each other after 2-week storage. These results suggested that there was an erosion and degradation of PLGA nanoparticles during storage. Ibuprofen-loaded PLGA nanoparticles have been successfully prepared by o/w single emulsion evaporation method. During the stability study, a faster degradation rate compared to non-loaded PLGA nanoparticles was exhibited, showing that Ibuprofen increased the degradation rate of PLGA nanoparticles. According to the results of drug releasing study, PLGA nanoparticles exhibiting a slower drug release rate than pure drug which proved that drug-nanoparticule system could effectively increase the stability of drugs. PLGA polymer is a potential material for drug delivery system.
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    Too large to fit? Recent developments in macromolecular imprinting.
    (Elsevier Science B.V., Amsterdam., 2008-04-01T00:00:00Z) Ge, Yi; Turner, Anthony P. F.
    Molecular imprinting involves the synthesis of polymers in the presence of a template to produce complementary binding sites with specific recognition ability. The technique has been successfully applied as a measurement and separation technology, producing a uniquely robust and antibody-like polymeric material. Low molecular weight molecules have been extensively exploited as imprint templates, leading to significant achievements in solid-phase extraction, sensing and enzyme-like catalysis. By contrast, macromolecular imprinting remains underdeveloped, principally because of the lack of binding site accessibility. In this review, we focus on the most recent developments in this area, not only covering the widespread use of biological macro-templates but also highlighting the emerging use of synthetic macro-templates, such as dendrimers and hyperbranched polymers.
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    Toxicity evaluation and medical application of multi-walled carbon nanotubes
    (Cranfield University, 2015-01) Zhou, Lulu; Ge, Yi; Lunec, Joseph
    Carbon nanotubes (CNTs) are of special interest to industry and they have been increasingly utilised as advanced nanovectors in drug/gene delivery systems. They possess significant advantages including high surface area, welldefined morphologies, unique optical property, superior mechanical strength and thermal conductivity. However, despite their unique and advanced physicochemical properties, the low compatibility of some of those materials [e.g. multiwalled CNTs (MWCNTs)] in most biological and chemical environments has also generated some serious health and environment concerns. Chemical functionalization broadens CNT applications, conferring new functions, and at the same time was found potentially altering toxicity. Although considerable experimental data related to functionalised CNT toxicity, at the molecular and cellular levels, have been reported, there is very limited information available for the corresponding mechanism involved (e.g. cell apoptosis, genotoxicity. The toxicity of carbon nanotubes has been confirmed on many cell lines including A549 (lung cancer cell line) and MRC-5 (lung fibroblasts). However, the sensitivity of each cell line in terms of cellular morphology, apoptosis and DNA damage are still unknown. In this report the different levels of cellular response to oxidative stress and phagocytosis have been investigated in A549, MCF-7 and MRC-5 cell lines to better understand the mechanisms of the toxicity pathway. siRNA as an ideal personalized therapeutics can specifically regulate gene expression, but efficient delivery of siRNA is difficult while it has been shown that MWCNTs protect siRNA, facilitate entry into cells. In this study, we comprehensively evaluated the in vitro cytotoxicity of pristine and functionalized (-OH, -COOH) multi-wall carbon nanotubes (MWCNTs), via cell viability test, reactive oxygen species (ROS) generation test, cell apoptosis and DNA mutation detection, to investigate the non-toxic dose and influence of functional group in A549, MCF-7 and MRC-5 cells exposed to 1-1000 μg/mL MWCNTs from 6 to 72 hours. In addition, 84 toxicity related genes have been detected to investigate the change of RNA regulation after treatment with MWCNTs. The research findings suggest that functionalized MWCNTs are more genotoxic compared to their pristine form, and the level of both dose and dispersion in the matrix used should be taken into consideration before applying further clinical applications of MWCNTs. Among all three cell lines, MCF-7 was the most sensitive to cell death and DNA damage induced by pristine carbon nanotubes. The majority of MCF-7 cell death was in necrotic. In A549 cells, apoptosis played a notable role in cytotoxicity. MRC-5 didn’t show significant cell loss or membrane damage, which might be explained by its low cell growth rate, notably however, a great reduction of the F-actin and attachment points was observed after treatment which indicates that MRC-5 cells are under very unhealthy condition and less attached to the bottom of flasks. Despite their toxicity, which is still being researched, carbon nanotubes have a great potential in clinical medicine. Thus, understanding the sensitivity of different cell lines could offer a more individualized approach for future treatment regimes. In regards to gene delivery, MWCNTs were found to be less toxic than chemical agents (positive control) without weakening the delivery efficiency, which proves that MWCNTs have a good potential in medicine area.