1,721,011 research outputs found
Sodium carbonate mediated synthesis of iron oxide nanoparticles to improve magnetic hyperthermia efficiency and induce apoptosis
No full textIron oxide nanoparticles are a popular choice for many current technologies, especially those with applications in biology and medicine. Novel syntheses that aim to improve their physicochemical properties, or adapt them to distinct practical applications, are constantly being reported. However, the reproducibility of these methods is not commonly studied, leading to promising products that have little chance of being commercially manufactured. Adherence to good manufacturing practice standards is a decisive factor in determining whether a material may be granted regulatory approval for industrial or clinical use. As such, tight control on the synthetic conditions is crucial to obtain consistent products. In this work initial experimentation was focused on the use of sodium carbonate―an environmentally friendly base―for the synthesis of iron oxide nanoparticles. Mild reaction conditions and slow kinetics allowed for the study of the reaction mechanism and led to controllable and reproducible results. However, functionalised suspensions could not be obtained due to the adsorption of carbonate onto the nanoparticle surface. A microwave reactor was then introduced to take advantage of the surface selective heating effect, aiding ligand exchange and enabling the production of nanoparticles with a range of surface functionalities. Their potential for magnetic hyperthermia, a promising therapeutic tool for the treatment of cancer, was investigated. Citric acid-iron oxide nanoparticles exhibited the highest heating performance, with an intrinsic loss power of 4.1 nHm2kg-1, which is 30% better than the best commercially available equivalent. Finally, their potential to treat near-surface or accessible tumours was tested in vitro on a human melanoma DX3 cell model. The results showed a controllable cell death via selective apoptosis or necrosis depending on the field and frequency applied. Time-lapse fluorescent microscopy experiments allowed the first direct observation of magnetic hyperthermia in adherent cells, where total-population cell death by apoptosis was observed
Design, development and testing of a magnetic haemofilter for clinical applications
Get PDFAbstract In this thesis I present the magnetic haemofilter - a novel medical device designed to remove magnetic materials directly from a patient's bloodstream. The haemofilter is a high gradient magnetic separator incorporated into an extra-corporeal loop. A patient's blood is constantly circulated through the device, which magnetically captures and retains target agents while the rest of the blood returns to the patient unharmed. Clinical versions of the device were conceived, designed and modelled. Small scale versions, designed to mimic the performance of the clinical designs, were manufactured using 3D printing and tested in benchtop in vitro experiments. Abstract Many potential applications for the device are envisioned, and justified with an extensive literary review of magnetic labelling, the process of binding magnetic particles to specific targets to enable their separation. The device has significant potential as a platform technology enabling these varied applications. In this project, however, malaria was chosen as the primary application. Malaria infected red blood cells are paramagnetic, so their separation does not require magnetic labelling - the haemofilter simply exploits their naturally occurring magnetic properties. Abstract The haemofilter was tested using samples of malaria infected blood filtered at a variety of flow rates, with a reduction in parasitaemia observed in every experiment at throughputs orders of magnitude higher than any previously reported clinical magnetic haemofiltration device. The results demonstrate that even without further optimisation, the clinical version of the device could halve a child's parasitaemia in less than 90 minutes. The flow rates used in the experiments, and those that could be used in the clinical versions, are orders of magnitude higher than any previously reported clinical magnetic haemofilter. Experiments on samples donated by malaria patients demonstrated that no other blood components are affected by the process. Abstract A commercial evaluation of the haemofilter as a medical device to treat malaria was conducted. The market analysis showed a large potential total addressable market, segmented into three principal patient populations. The product development and manufacturing costs were estimated and shown to be reasonable, while a financial analysis showed that a margin could be earned while still saving customers money. A route-to-market and commercialisation strategy is presented. Abstract I conclude that the magnetic haemofilter has the potential to deliver significant clinical benefits to a wide variety of malaria patients, saving lives in serious cases, providing a treatment option for currently untreatable patients, and speeding up recovery in uncomplicated cases, while improving the efficacy and eliminating the side-effects of pharmaceutical drugs
Applied synthesis and characterisation of nanoparticles
Get PDFThis thesis covers three areas of development of nanomaterials synthesis; namely the synthesis of superhydrophobic polymer-nanoparticle composites (chapter 3), the synthesis of doped quantum dots for catalysis and photoluminescence enhancement (chapter 4) and the synthesis of magnetic iron oxide nanoparticles from inexpensive, readily available reagents (chapter 5). Details of characterisation and analytical techniques and synthetic methods used are given in chapter 2, and the thesis summarised in chapter 6. Superhydrophobic polymer-nanoparticle composites represent a class of material which combine the superhydrophobicity of the polymer with the functionality of incorporated nanoparticles. Reactive oxygen species generated by photocatalytic nanoparticles degrade organic matter, and thus degrade the polymer, resulting in a loss of superhydrophobicity. In this chapter, a general method for the incorporation of hydrophobically ligated nanoparticles into a superhydrophobic poly(dimethylsiloxane) polymer matrix via AACVD is demonstrated. This resulted in a highly effective, robust titania nanoparticle-poly(dimethylsiloxane) composite for photocatalysis, along with, to the best of the author's knowledge, the first superparamagnetic-superhydrophobic polymer composite. Chapter 4 deals with the synthesis and characterisation of a quantum dot based photoactivated catalyst vector which releases Cu+ via UV irradiation, the first of its kind. The catalytic activity was evaluated using “click” chemistry under UV irradiation, with quantum dots being recoverable and able to undergo several catalytic cycles. A mechanism for the photoluminescence and copper release is also postulated. The copper is incorporated into the shells of quantum dots via the decomposition of single source metal-dithiocarbamates. Chapter 5 details a method for the synthesis of iron oxide nanoparticles for magnetic hyperthermia, but from reagents obtained from the high street. A low cost synthesis was developed and the resulting nanoparticles functionalised with an amphiphilic polymer and tested for magnetic hyperthermia
Anisotropy field measurement in barium ferrite powders by applied field MSssbauer spectroscopy
Get PDFA new method for measuring magnetic anisotropy in ferrimagnetic powders using applied field Mossbauer spectroscopy has been developed. The method is based on using a uniaxial anisotropy mean-field model to calculate the equilibrium spin orientations as a function of applied field and compute the corresponding Mossbauer spectra. A variety of asymmetric broad line profiles are predicted which are sensitively dependent on the magnetization and the exchange and anisotropy terms. In principle the technique enables the determination of individual sublattice anisotropies, although in the case of pure and Co-Ti substituted barium ferrite the sublattice anisotropies are found to be experimentally indistinguishable. A mean anisotropy is obtained which compares favourably with the results of other measurements on barium ferrite
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Using the 'dispersion-retention-formulation method' to estimate clinical and preclinical dosage limits for interstitial nanomedicines or agents
Get PDFWe propose the “DRF method” for estimating dosage limits for interstitially administered therapeutic or diagnostic nanomedicines or agents from three characteristic parameters that can be experimentally determined from in vivo data. These are: (i) the dispersion of the injected fluid around the injection site; (ii) the retention of the injected fluid at the injection site; and (iii) the formulation characteristics of the fluid with respect to local and systemic tolerability. We present formulae that allow dose-limit estimates to be made for any preclinical model, as well as for clinical studies. We illustrate the DRF method for the case of iron-oxide-based magnetic fluids, with reference to the published dose limits of regulatory-body-approved magnetic nanoparticles for MRI contrast enhancement, sentinel node detection, iron replacement therapy, and magnetic thermoablation
Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models
Get PDFWe offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field. We show that under appropriately chosen conditions a therapeutic temperature rise is achievable in clinically relevant situations. We also show that in such cases it may paradoxically be harder to achieve the same therapeutic temperature rise in a preclinical model. We comment on the implications for the evidence-based translation of hyperthermia based interventions from the laboratory to the clinic
Biomedical applications of high gradient magnetic separation: progress towards therapeutic haeomofiltration
Get PDFHigh gradient magnetic separation is a well-established technology in the mineral processing industry, and has been used for decades in the bioprocessing industry. Less well known is the increasing role that high gradient magnetic separation is playing in biomedical applications, for both diagnostic and therapeutic purposes. We review here the state of the art in this emerging field, with a focus on therapeutic haemofiltration, the key enabling technologies relating to the functionalisation of magnetic nanoparticles with target-specific binding agents, and the development of extra-corporeal circuits to enable the in situ filtering of human blood
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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