Yongbai Yin

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines.

Covalent immobilisation of tropoelastin on a plasma deposited interface for enhancement of endothelialisation on metal surfaces

Currently available endovascular metallic implants such as stents exhibit suboptimal biocompatibility in that they re-endothelialise poorly leaving them susceptible to thrombosis. To improve the interaction of these implants with endothelial cells we developed a surface coating technology, enabling the covalent attachment of biomolecules to previously inert metal surfaces. Using horseradish peroxidase as a probe, we demonstrate that the polymerised surface can retain the presentation and activity of an immobilised protein. We further demonstrated the attachment of tropoelastin, an extracellular matrix protein critical to the correct arrangement and function of vasculature. Not only it is structurally important, but it plays a major role in supporting endothelial cell growth, while modulating smooth muscle cell infiltration. Tropoelastin was shown to bind to the surface in a covalent monolayer, supplemented with additional physisorbed multilayers on extended incubation. The physisorbed tropoelastin layers can be washed away in buffer or SDS while the first layer of tropoelastin remains tightly bound. The plasma coated stainless steel surface with immobilised tropoelastin was subsequently found to have improved biocompatibility by promoting endothelial cell attachment and proliferation relative to uncoated stainless steel controls. Tropoelastin coatings applied to otherwise inert substrates using this technology could thus have broad applications to a range of non-polymeric vascular devices.

The immobilization of recombinant human tropoelastin on metals using a plasma-activated coating to improve the biocompatibility of coronary stents

Current endovascular stents have sub-optimal biocompatibility reducing their clinical efficacy. We previously demonstrated a plasma-activated coating (PAC) that covalently bound recombinant human tropoelastin (TE), a major regulator of vascular cells in vivo, to enhance endothelial cell interactions. We sought to develop this coating to enhance its mechanical properties and hemocompatibility for application onto coronary stents. The plasma vapor composition was altered by incorporating argon, nitrogen, hydrogen or oxygen to modulate coating properties. Coatings were characterized for 1) surface properties, 2) mechanical durability, 3) covalent protein binding, 4) endothelial cell interactions and 5) thrombogenicity. The N(2)/Ar PAC had optimal mechanical properties and did not delaminate after stent expansion. The N(2)/Ar PAC was mildly hydrophilic and covalently bound the highest proportion of TE, which enhanced endothelial cell proliferation. Acute thrombogenicity was assessed in a modified Chandler loop using human blood. Strikingly, the N(2)/Ar PAC alone reduced thrombus weight by ten-fold compared to 316L SS, a finding unaltered with immobilized TE. Serum soluble P-selectin was reduced on N(2)/Ar PAC and N(2)/Ar PAC + TE (p < 0.05), consistent with reduced platelet activation. We have demonstrated a coating for metal alloys with multifaceted biocompatibility that resists delamination and is non-thrombogenic, with implications for improving coronary stent efficacy.

CHILDHOOD INCIDENCE OF ACUTE LYMPHOBLASTIC LEUKAEMIA AND EXPOSURE TO BROADCAST RADIATION IN SYDNEY - A SECOND LOOK

Introduction: Recent findings of an apparent association between incidence of childhood leukaemia and radio frequency radiation (RFR) from television transmission antennas in Sydney, NSW, are examined.

Cerenkov-free scintillation dosimetry in external beam radiotherapy with an air core light guide

Plastic scintillators have many advantages for dosimetry in external beam radiotherapy. The current method of transmitting the scintillation light to a remote detector is through a solid core optical fibre. When exposed in a high energy therapeutic radiotherapy beam this fibre is subject to an unwanted background signal from Cerenkov light which can exceed the scintillation signal at characteristic angles. We have constructed a plastic scintillation dosimeter that uses an air core light guide to transport the light from the scintillator to the light detector. We show that there is sufficient signal propagation in the air core light guide to allow the scintillator signal to be carried outside the primary beam of a radiotherapy linear accelerator and for a dosimeter to be constructed using a scintillator inserted into the end of the light guide. Studies of the background light generated in the air core light guide, as a function of the angle between the beam and the fibre axis, show that there is no characteristic Cerenkov peak generated in the air core. Depth dose measurements using the air core scintillation dosimeter with no correction for Cerenkov are compared to ionization chamber measurements for a 6 MV photon beam and a 9 MeV electron beam.

Interactions of the directed plasma from a cathodic arc with electrodes and magnetic fields

Curved magnetic ducts are frequently used to remove macroscopic-sized droplets from the plasma stream of cathodic vacuum arcs. The plasma of a cathodic vacuum arc in a magnetic filter is characterized by a strongly directional ion velocity (corresponding to 20-100 eV) and magnetized electrons. In the first section of this paper the effects of these features on the I-V characteristic curves of planar probes are identified and explained using a simple model. This is then used to interpret the interaction of the plasma with the walls of a biased quarter torus duct. Two small electrodes placed on the outer and inner sections of the curved duct wall show that the I-V characteristic is determined primarily by the electron-ion current balance at the wall on the outside of the curve. The application of a bias to a planar electrode on the outer wall section was found to give the same increase in throughput as a positive bias applied to the entire duct with the advantage of a much smaller electron current being drawn by the biasing power supply. The improvement in duct throughput achievable with positive-biasing of the duct wall was found to depend on both the configuration and strength of the magnetic field in the quarter torus filter. The plasma density profile and potential were unaffected by the application of the bias.

A study of filter transport mechanisms in filtered cathodic vacuum arcs

Ion transport in a magnetically filtered cathodic arc thin film deposition system is investigated. The plasma floating potential, ion current and deposition rate profiles are used to show that the ion density profile is a function of the magnetic field configuration alone although the magnitude of the ion density increases linearly with magnetic field strength. The magnetic mirror effect, electron diffusion and ion centrifugal drift are identified as the dominant loss mechanisms. The results can be used to design optimal filter systems and to control deposition rate profiles. The effect of reactive gas pressure is also examined.

Silvery Fish Skin as an Example of a Chaotic Reflector

The silvery reflectance in fish skin is studied using an idealized model of the two optical components, guanine and cytoplasm. A structure in which the thickness of both components are randomized over an interval gives a calculated reflectance in good agreement with the measured reflectance of two species in the family Trichiuridae, including the behaviour in the infrared. Existing ideas based on quarter-wave stacks, either tuned to different wavelengths or with a progression of optical thickness with depth, have been shown to be unsatisfactory. The random or ‘chaotic’ structure is confirmed by electron microscopy of cross sections of fish skin. The random structure is an example of the phenomenon of optical localization in a biological system.

A prototype scintillation dosimeter customized for small and dynamic megavoltage radiation fields

A prototype plastic scintillation dosimeter has been developed with a small sensitive volume, rapid response and good dosimetric performance. The novelty of this design is the use of an air core light guide to transport the scintillation signal out of the primary radiation field. The significance of this innovation is that it eliminates the Cerenkov background signal that is generated in conventional optical fibres. The dosimeter performance was compared to existing commercial dosimeters in 6 MV and 18 MV photon beams and 6 MeV and 20 MeV electron beams, in both static and dynamic fields. The dosimeter was tested in small static fields and in dynamically delivered fields where the detector volume is shielded, while the stem is irradiated. The depth dose measurements for the photon beams agreed with ionization chamber measurements to within 1.6%, except in the build-up region due to positional uncertainty. For the 6 MeV and 20 MeV electron beams, the percentage depth dose measurements agreed with the ionization chamber measurements to within 3.6% and 4.5%, respectively. For field sizes of 1 cm x 1 cm and greater, the air core dosimeter readings agreed with diamond detector readings to within 1.2%. The air core dosimeter was accurate in dynamically delivered fields and had no measurable stem effect. The air core dosimeter was accurate over a range of field sizes, energies and dose rates, confirming that it is a sensitive and accurate dosimeter with high spatial resolution suitable for use in megavoltage photon and electron beams.

New technology for PACVD

Abstract Plasma-assisted chemical vapour deposition (PACVD) has many advantages for the deposition of thin films. The use of ions for the energetic bombardment of the film during growth is an important technique for producing dense structures. This paper discusses recent progress in the understanding of the effects of energetic bombardment on the stress levels and structure of films produced by plasma deposition processes. Diagnostic equipment, such as the in situ ellipsometer, energy selecting mass spectrometer and residual gas analyser, enables the PACVD process to be closely monitored so that conditions at the growth surface can be accurately controlled. New plasma sources, such as the helicon plasma source, give increased ion fluxes. The cathodic arc source is also an intense source of highly ionized plasma which can be used for PACVD. The deposition of rugate optical structures based on SiO x N y can be carried out using a PACVD process in which the refractive index profile is created by the computer control of gas flows. The helicon plasma source is useful for the deposition of SiO 2 films and has been adapted for use in an ion plating process for the deposition of cubic phase BN. The deposition of amorphous hydrogenated carbon films by PACVD of acetylene in a cathodic arc has been shown to be possible and demonstrates the effect of using a highly ionized plasma for PACVD.