Surface integrity study for FC300 cast iron using TiAIN ball end mill

Finishing of FC300 gray cast iron predominantly done by manual polishing. Study the surface integrity of FC300 after machining is crucial to investigate the surface characteristics before polishing. This work aims to investigate the surface profiles and subsurface alterations induced by milling of FC300 gray cast iron using TiAlN Ball end mill. Machining trials were performed using CNC variaxis machine in dry condition at the cutting speeds of 66-99 m/min, feed rates of 0.27-0.42 mm/tooth and constant depth of cut of 0.1 mm. The results shows that the surface roughness decreased as the cutting speed increased from 66 m/min to 88 m/min. Smooth and shiny surface profiles appeared at the lower cutting speed of 66 m/min due to effect of lubrication layer that formed from the small fragmented graphite flakes. When the cutting speed increased to 99 m/min, surface profiles appeared with smeared and large graphite flakes probably due to higher rotational impact from the cutting tool. Analysis of subsurface microstructure observed bending effects at the region where worn cutting tool applied. Severe crack nucleation’s were evidence to reflect severe rubbing action from worn cutting tool

Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an external oscillating magnetic field. As a technique, it produces highly sensitive radiation-free tomographic images with absolute quantitation. Coupled with a high contrast, as well as zero signal attenuation at-depth, there are essentially no limitations to where can be imaged within the body. These characteristics enable various biomedical applications of clinical interest. In the opening sections of this review, the principles of image generation are introduced, along with a detailed comparison of the fundamental properties of this technique with other common imaging modalities. The main feature is a presentation on the up-to-date literature for the development of SPIONs tailored for improved imaging performance, and developments in the current and promising biomedical applications of this emerging technique, with a specific focus on theranostics, cell tracking and perfusion imaging. Finally, we will discuss recent progress in the clinical translation of MPI. As signal detection in MPI is almost entirely dependent on the properties of the SPION employed, this work emphasises the importance of tailoring the synthetic process to produce SPIONs demonstrating specific properties and how this impacts imaging in particular applications and MPI’s overall performance

Developing superparamagnetic iron oxide nanoparticles as targeted cancer nanomedicine

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have unique properties with potential application in targeted cancer treatment; including the ability to generate heat when placed in an external alternating magnetic field. However, challenges such as rapid circulatory clearance by the reticuloendothelial system (RES), the need for effective functionalisation with cancer-targeting agents and heterogeneity of SPIONs, remain to be overcome. The work in this thesis aims to develop SPIONs by addressing these challenges. Ferucarbotran (Resovist®), a clinically approved MRI contrast SPION with excellent heating potential was investigated. Three main hypotheses were tested; that RES uptake of SPIONs could be blocked in vitro and in vivo, that specific targeting could be achieved by functionalising SPIONs with non-immunoglobulin cancer-targeting proteins and that product heterogeneity could be addressed by physical separation. Studies included: (i) Interactions of SPIONs with different cell types (ii) Blocking cell uptake using polysaccharide derivatives (iii) Conjugation strategies to link SPIONs to near-infrared dyes to trace their blood levels (iv) Enhancing the circulatory retention of SPIONs via RES blocking (v) Site-specific conjugation methods to functionalise SPIONs with cancer targeting protein (vi) Cellular- and immuno-assays to test the binding of functionalised SPIONs to target antigen (vii) Size exclusion chromatography (SEC) to fractionate SPIONs. Results showed that Ferucarbotran was unspecifically internalised by all tested cell lines. A range of sulfated polysaccharides were shown to block this uptake in vitro and in vivo leading to prolonged circulatory times. Ferucarbotran was successfully functionalised with cancer-targeting protein and bound specifically to target antigen in ELISA. Cellular assays with a range of cell lines revealed the generalised altered behaviour of SPIONs upon surface modification with proteins. SEC successfully fractionated Ferucarbotran into more homogeneous products with improved heating properties. In conclusion, these results are consistent with the proposed hypotheses and form a platform for addressing the challenges of SPIONs-based cancer nanomedicine

Magnetic Hyperthermia for the Treatment of Glioblastoma

Introduction: Glioblastoma, the most common primary adult brain malignancy, is an aggressive tumour with median survival of around one year. Despite extensive research there has been minimal improvement in prognosis and innovative new treatments are urgently required. The research within this thesis focussed on designing a novel therapeutic approach using nanotechnology to achieve in-situ immune stimulation mediated by localised hyperthermia and characterising the effects of hyperthermia within the tumour microenvironment (TME). Methods: In-situ heating was generated using superparamagnetic iron-oxide nanoparticles (SPIONs) stimulated by an alternating magnetic field (AMF); a combined process known as magnetic hyperthermia. Candidate SPIONs were first tested for biocompatibility and favourable heating properties. In-vivo experiments utilised the immunocompetent GL261 glioblastoma model and included: (i) Testing reticuloendothelial system blocking, and direct intratumoural injection to obtain sufficient intratumoural SPION concentrations; (ii) Utilising 89Zr-labelled SPIONs to evaluate in-vivo fate using PET-CT Imaging; (iii) Evaluation of SPION in-vivo heating ability using thermal imaging; (iv) Tumour growth and timed immunohistochemical (IHC) response analysis; (v) Flow cytometry analysis of the tumour infiltrating lymphocyte (TIL) populations following treatment and (vi) testing a combination therapeutic approach combining magnetic hyperthermia with immune checkpoint inhibition. Results: Perimag-COOH was identified as the lead candidate SPION, and intratumoural injection chosen as the optimal method to obtain sufficient intratumoural SPION concentrations. Perimag-COOH remained within the tumour following injection and retained ability to generate AMF-induced heat for at least 72 h post injection. Digital image analysis of IHC demonstrated a specific, localised, heat-shock protein response following hyperthermia. Tumour growth inhibition was observed up to one week following treatment and tumour flow cytometry analysis revealed changes in TIL populations suggestive of an immune response, providing a rational for a combination approach with immune checkpoint inhibition. Conclusions: SPION mediated hyperthermia is achievable in-vivo and can generate TME changes suggestive of an anti-tumour immune response

Single-sided magnetic nanoparticles imaging scanner for early detection of breast cancer

Electromagnetic coils form the basis of magnetic particle imaging (MPI) scanners. Previous scanner designs employ Helmholtz coil arrangement which has low sensitivity and high cost of fabrication. Furthermore, the scanners have long signal acquisition time and high memory requirement. This research focuses on developing a simple, low-cost and low memory demanding one-dimensional MPI scanner capable of imaging the position and concentration of magnetic nanoparticles (MNPs), using electromagnetic coils in the form of solenoids. The scanner produces an oscillatory magnetic field to excite the MNPs and a static magnetic field to confine the region of interest. The MNPs reacted with a nonlinear magnetisation response, inducing a voltage signal that was measured with an appropriate gradiometer pickup coil. In Fourier space, the received voltage signal consists of the fundamental excitation frequency and harmonics. This research utilises the second harmonic response of the MNPs to determine their position and concentration. Analogue Bandpass and Bandstop filters were designed for signal excitation and reception. Resovist and Perimag MNPs in liquid and immobilised form were used as tracer materials, which were moved to different spatial positions through the field of view (FOV), to record the induced voltages. The magnitude response of the Bandpass filter with 22.8 kHz fundamental frequency shows a flat amplitude in the passband with a smooth roll-off rate of ±80 dB/pole, while the Bandstop filter efficiently attenuates the fundamental frequency and passed the 45.6 kHz second harmonic frequency. Results of the excitation coil design revealed that a magnetic field within the range of 0.8 mT to 4.4 mT was obtained, while a voltage in microvolts range was induced in the gradiometer pickup coil. The contour maps derived from imaging one and two samples of the MNPs in the XY-plane revealed their position and shape. Additionally, the average threshold of the peak signal amplitude was obtained as 10.63 μV that would indicate the presence of MNPs concentration sufficient for cancer detection. The developed single-sided MPI scanner has a spatial resolution of less than 1 mm, a pixel resolution of 51.5 megapixels and 42.1 ms image acquisition time. Thus, the outcome of this research showed that the developed single-side MPI scanner has a potential in the detection of MNPs, which could help in sentinel lymph node biopsy for breast cancer diagnosis

Microgel iron oxide nanoparticles for tracking of stem cells through magnetic resonance imaging

Ph.DDOCTOR OF PHILOSOPH

Development of reflectance imaging methodologies to investigate super-paramagnetic iron oxide nanoparticles

Engineered nanoparticles, such as super paramagnetic iron oxide nanoparticles (SPIONs) offer significant benefits for the development of various diagnostic and therapeutic strategies. Limitations of existing imaging methodologies in the study of NPs, such as the effects of fluorescent labelling and diffraction limited resolution, and the advantages that visualization of spatial localization can offer in studies, increases the demand for new and optimized imaging routines. Reflectance Confocal Microscopy (RCM) methods were optimized and Reflectance Structured Illumination Microscopy (R-SIM) was introduced, offering a two fold increase in resolution - particularly advantageous for NP quantification and localization studies. Analysis routines were developed to enable the automated quantification of NP presence within cells via the different methodologies. Correlative procedures were also established for imaging the same sample with different reflectance methods and TEM, maximizing the information attainable from a single sample and allowing comparisons between the techniques for specific applications. These aforementioned optimized techniques were then applied to the determination of NP uptake and trafficking in cancer cell lines, and, in combination with siRNA, to ascertain proteins that are involved in the uptake process. Studies were also performed to model the degradative process of SPIONs within cellular compartments. This thesis thus provided several important tools for the future assessment of the efficacy and safety of NPs for clinical use, enabling quantitative analysis of uptake route, sub-cellular localization and NP intracellular fate

Polymer-coated iron oxide nanoparticles for medical imaging

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 144-157).One of the most versatile and safe materials used in medicine are polymer-coated iron oxide nanoparticles. This dissertation describes several formulations for in vivo imaging applications. The paramagnetic polymer-coated iron oxide nanoparticle aminoSPARK is used as a fluorescence-mediated tomography (FMT) imaging agent for stratification of prostate cancer tumors. This is achieved by conjugating it to a peptide that targets SPARC (secreted protein acidic rich in cysteine), a biomarker protein associated with aggressive forms of prostate cancer. Several types of polymer coatings for iron oxide nanoparticles have been systematically explored using a novel high-throughput screening technique to optimize coating chemistries and synthetic conditions to produce nanoparticles with maximum stability and ability to lower T2 contrast for MR imaging (R2, or relaxivity). Carboxymethyl dextran emerged from the screen as an ideal coating for superparamagnetic iron oxide nanoparticles. A commercially available, FDA-approved nanoparticle with similar surface chemistry, Feraheme, was chosen as a platform nanoparticle for further development. This work presents the first instance of chemical modification of Feraheme, making it more amenable to bioconjugation by converting its free carboxyl groups to free amine groups. This amine-functionalized Feraheme nanoparticle (amino-FH) is then used as a base nanoparticle to which various targeting and reporting functionalities can be added. A FH-based nanoparticle that can be used for cell loading is synthesized by covalently combining Feraheme with protamine, a pharmaceutical that also acts as a membrane translocating agent. A rhodamine-protamine conjugate is synthesized and then covalently bound to amino-FH using carbodiimide (CDI) chemistry. This results in a magnetofluorescent cell-labeling nanoparticle (ProRho-FH) that is readily taken up by mouse mesenchymal stem cells and U87 glioma cells. ProRho-FH can be used to non-invasively track cells for development and monitoring of cell-based therapies or for further investigation of biological mechanisms such as cell migration, tumor growth, and metastasis. This combination of two FDA-approved, commercially available materials to yield a superparamagnetic and fluorescent cell labeling nanoparticle is an excellent alternative to the recently discontinued Feridex. All polymer-coated iron oxide nanoparticles used in this dissertation were thoroughly characterized to fully understand their physicochemical and magnetic properties.by Suelin Chen.Ph.D

High-Resolution 1.5-Tesla Magnetic Resonance Imaging for Tissue-Engineered Constructs: A Noninvasive Tool to Assess Three-Dimensional Scaffold Architecture and Cell Seeding

International audienceTissue-engineered scaffolds are made of biocompatible polymers with various structures, allowing cell seeding, growth, and differentiation. Noninvasive imaging methods are needed to study tissue-engineered constructs before and after implantation. Here, we show that high-resolution magnetic resonance imaging (MRI) performed on a clinical 1.5-T device is a reliable technique to assess three-dimensional structures of porous scaffolds and to validate cell-seeding procedures. A high-temperature superconducting detection coil was used to achieve a resolution of 30Â30Â30 mm 3 when imaging the scaffolds. Three types of structures with tuneable architectures were prepared from naturally derived polysaccharides and evaluated as scaffolds for mesenchymal stem cell (MSC) culture. To monitor cell seeding, MSCs were magnetically labeled using simple incubation with anionic citrate-coated iron-oxide nanoparticles for 30 min. Iron uptake was quantified using single-cell magnetophoresis, and cell proliferation was checked for 7 days after labeling. Three-dimensional (3D) microstructures of scaffolds were assessed using MRI, revealing lamellar or globular porous organization according to the scaffold preparation process. MSCs with different iron load (5, 12 and 31 pg of iron per cell) were seeded on scaffolds at low density (132 cells=mm 3) and detected on 3D gradient-echo MR images according to phase distortions and areas of intensely low signal, whose size increased with cell iron load and echo time. Overall signal loss in the scaffold correlated with the number of seeded cells and their iron load. Different organizations of cells were observed depending on the scaffold architecture. After subcutaneous implantation in mice, scaffolds seeded with labeled cells could be distinguished in vivo from scaffold with nonlabeled cells by observation of signal and phase heterogeneities and by measuring the global signal loss. High-resolution 1.5-T MRI combined with efficient intracellular contrast agents shows promise for noninvasive 3D visualization of tissue-engineered constructs before and after in vivo implantation