It is well established that cells, tissues, and organisms exposed to low doses of ionizing radiation can induce effects in non-irradiated neighbors (non-targeted effects or NTE), but the mechanisms ...remain unclear. This is especially true of the initial steps leading to the release of signaling molecules contained in exosomes. Voltage-gated ion channels, photon emissions, and calcium fluxes are all involved but the precise sequence of events is not yet known. We identified what may be a quantum entanglement type of effect and this prompted us to consider whether aspects of quantum biology such as tunneling and entanglement may underlie the initial events leading to NTE. We review the field where it may be relevant to ionizing radiation processes. These include NTE, low-dose hyper-radiosensitivity, hormesis, and the adaptive response. Finally, we present a possible quantum biological-based model for NTE.
Gold is the most widely used electrode material for bioelectronic applications due to its high electrical conductivity, good chemical stability and proven biocompatibility. However, it adheres only ...weakly to widely used substrate materials such as glass and silicon oxide, typically requiring the use of a thin layer of chromium between the substrate and the metal to achieve adequate adhesion. Unfortunately, this approach can reduce biocompatibility relative to pure gold films due to the risk of the underlying layer of chromium becoming exposed. Here we report on an alternative adhesion layer for gold and other metals formed from a thin layer of the negative-tone photoresist SU-8, which we find to be significantly less cytotoxic than chromium, being broadly comparable to bare glass in terms of its biocompatibility. Various treatment protocols for SU-8 were investigated, with a view to attaining high transparency and good mechanical and biochemical stability. Thermal annealing to induce partial cross-linking of the SU-8 film prior to gold deposition, with further annealing after deposition to complete cross-linking, was found to yield the best electrode properties. The optimized glass/SU8-Au electrodes were highly transparent, resilient to delamination, stable in biological culture medium, and exhibited similar biocompatibility to glass.
We characterize for the first time the emission of acoustic waves from cultured cells irradiated with X-ray photon radiation.
Human cancer cell lines (MCF-7, HL-60) and control cell-free media were ...exposed to 1 Gy X-ray photons while recording the sound generated before, during and after irradiation using custom large-bandwidth ultrasound transducer. The effects of dose rate and cell viability were investigated.
We report the first recorded acoustic signals captured from a collective pressure wave response to ionizing irradiation in cell culture. The acoustic signal was co-terminous with the radiation pulse, its magnitude was dependent on radiation dose rate, and live and dead cells showed qualitatively and quantitatively different acoustic signal characteristics. The signature of the collective acoustic peaks was temporally wider and with higher acoustic power for irradiated HL-60 than for irradiated MCF-7.
We show that X-ray irradiation induces two cultured cancer cell types to emit a characteristic acoustic signal for the duration of the radiation pulse. The rapid decay of the signal excludes acoustic emissions themselves from contributing to the inter-organism bystander signal previously reported in intact animals, but they remain a potential component of the bystander process in tissues and cell cultures. This preliminary study suggests that further work on the potential role of radiation-induced acoustic emission (RIAE) in the inter-cellular bystander effect is merited.
The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale ...data sets are processed, analyzed, and interpreted. The 67
th
Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications. This article summarizes three of those presentations regarding recent developments for metadata processing and ontological formalization, data mining for radiation outcomes in pediatric oncology, and imaging in lung cancer.
Conjugated polymers are increasingly exploited for biomedical applications. In this work, we explored the optical characteristics of conjugated polymers of variable chemical structures at multiple ...levels relevant to biological interfacing, from fluorescence yield to their influence on cellular membrane potential. We systematically compared the performance of conjugated polymer as cast thin films and as nanoparticles stabilized with amphiphilic polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA). We assessed in both the dark and under illumination the stability of key optoelectronic properties in various environments, including air and biologically relevant physiological saline solutions. We found that photoreduction of oxygen correlates with nanoparticle and film degradation in physiologically relevant media. Using patch-clamp recordings in cell lines and primary neurons, we identified two broad classes of membrane potential response, which correspond to photosensitizer- and photothermal-mediated effects. Last, we introduced a metric named OED
50
(optical energy for 50% depolarization), which conveys the phototoxic potency of a given agent and thereby its operational photo-safety profile.
Optogenetics combines optics and genetics to enable minimally invasive cell-type-specific stimulation in living tissue. For the purposes of bio-implantation, there is a need to develop soft, ...flexible, transparent and highly biocompatible light sources. Organic semiconducting materials have key advantages over their inorganic counterparts, including low Young's moduli, high strain resistances, and wide color tunability. However, until now it has been unclear whether organic light emitting diodes (OLEDs) are capable of providing sufficient optical power for successful neuronal stimulation, while still remaining within a biologically acceptable temperature range. Here we investigate the use of blue polyfluorene- and orange poly(p-phenylenevinylene)-based OLEDs as stimuli for blue-light-activated Sustained Step Function Opsin (SFFO) and red-light-activated ChrimsonR opsin, respectively. We show that, when biased using high frequency (multi-kHz) drive schemes, the OLEDs permit safe and controlled photostimulation of opsin-expressing neurons and were able to control neuronal firing with high temporal-resolution at operating temperatures lower than previously demonstrated.
π-Conjugated polymer nanoparticles (CPNs) are under investigation as photoluminescent agents for diagnostics and bioimaging. To determine whether the choice of surfactant can improve CPN properties ...and prevent protein adsorption, five nonionic polyethylene glycol alkyl ether surfactants were used to produce CPNs from three representative π-conjugated polymers. The surfactant structure did not influence size or yield, which was dependent on the nature of the conjugated polymer. Hydrophobic interaction chromatography, contact angle, quartz crystal microbalance, and neutron reflectivity studies were used to assess the affinity of the surfactant to the conjugated polymer surface and indicated that all surfactants were displaced by the addition of a model serum protein. In summary, CPN preparation methods which rely on surface coating of a conjugated polymer core with amphiphilic surfactants may produce systems with good yields and colloidal stability in vitro, but may be susceptible to significant surface alterations in physiological fluids.
We report optical brain imaging using a semi-transparent organic light-emitting diode (OLED) based on the orange light-emitting polymer (LEP) Livilux PDO-124. The OLED serves as a compact, extended ...light source which is capable of uniformly illuminating the cortical surface when placed across a burr hole in the skull. Since all layers of the OLED are substantially transparent to photons with energies below the optical gap of the LEP, light emitted or reflected by the cortical surface may be efficiently transmitted through the OLED and into the objective lens of a low magnification microscope ('macroscope'). The OLED may be placed close to the cortical surface, providing efficient coupling of incident light into the brain cavity; furthermore, the macroscope may be placed close to the upper surface of the OLED, enabling efficient collection of reflected/emitted light from the cortical surface. Hence the use of a semi-transparent OLED simplifies the optical setup, while at the same time maintaining high sensitivity. The OLED is applied here to one of the most demanding forms of optical brain imaging, namely extrinsic optical imaging involving a voltage sensitive dye (VSD). Specifically, we carry out functional imaging of the primary visual cortex (V1) of a rat, using the voltage sensitive dye RH-1691 as a reporter. Imaging through the OLED light-source, we are able to resolve small (~ 0.1 %) changes in the fluorescence intensity of the dye due to changes in the neuronal membrane potential following a visual stimulus. Results are obtained on a single trial basis -- i.e. without averaging over multiple measurements -- with a time-resolution of ten milliseconds.
Prototype fully biocompatible organic light-emitting diodes are investigated, with a view to creating a suitable and high-performance light source as a medical implant device. A selection of organic ...LED materials that have potential suitability for the biological environment are examined. First, the biocompatibility of selected OLED materials was evaluated by the study of cell adhesion and cytotoxicity of HeLa cells cultured on the candidate materials. Thus it was possible to design a device structure composed entirely of biocompatible materials. Second, the characterization of the electroluminescence properties of the prototype OLED is shown and its limitation evaluated. Third, the aqueous stability of the fully biocompatible light source is examined. There is strong evidence that fully biocompatible and stable light-emitting implant devices can be easily constructed. This is the first time a fully biocompatible organic light-emitting diode, albeit embryonic, is reported, with the hope that it may lead to further research to optimize the device performance. Some suggestions on suitable device properties towards in vivo transition are provided.
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