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Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed electric fields (PEFs) are promising for the improvement of treatment efficiency. However, they rely on rigid electrodes that cause acute and chronic damage, especially in soft tissues such as the brain. In this work, flexible electronics were used to deliver PEFs to tumors and the biological response was evaluated with fluorescent microscopy. Interdigitated gold electrodes on a thin, transparent parylene-C substrate were coated with the conducting polymer PEDOT:PSS, resulting in a conformable and biocompatible device. The effects of PEFs on tumors and their microenvironment were examined using various biological models. First, monolayers of glioblastoma cells were cultured on top of the electrodes to investigate phenomena in vitro. As an intermediate step, an in ovo model was developed where engineered tumor spheroids were grafted in the embryonic membrane of a quail. Due to the absence of an immune system, this led to highly vascularized tumors. At this early stage of development, embryos have no immune system, and tumors are not recognized as foreign bodies. Thus, they can develop fast while developing their own vessels from the existing embryo vascular system, which represents a valuable 3D cancer model. Finally, flexible electrode delivery of PEFs was evaluated in a complete organism with a functional immune system, using a syngenic, orthograft (intracranial) mouse model. Tumor spheroids were grafted into the brain of transgenic multi-fluorescent mice prior to the implantation of flexible organic electrode devices. A sealed cranial window enabled multiphoton imaging of the tumor and its microenvironment during treatment with PEFs over a period of several weeks.

Glioblastoma Multiforme is a highly lethal form of brain cancer, resistant to traditional therapeutic approaches and oftentimes hardly resectable. The application of pulsed electric fields (PEF) is gaining prominence as a highly effective approach for combating malignant tumors. However, PEF application at high voltages can generate reactive oxygen species through electrochemical events at electrodes, which can greatly affect intracellular processes and damage healthy cells. Here, we present an in depth study on the cellular impact of coating metal electrodes with an organic polymer PEDOT:PSS. We compared the effect of PEF application through coated and uncoated gold electrodes on the U87 human glioblastoma cell line. The results show that PEF application using PEDOT:PSS-coated electrodes does not induce intracellular ROS generation, even at high voltages, contrary to that observed with uncoated electrodes. PEF delivery with PEDOT:PSS coated electrodes results in minimal cell electroporation and a lower intracellular calcium response than uncoated metal electrodes. The application of the antioxidant MnTBAP allowed us to establish that superoxide generation is partially responsible for the higher intracellular calcium response observed in uncoated metal electrodes. The results demonstrate that PEDOT-coated electrodes allow for PEF application without intracellular ROS generation, with the trade-off being a diminished electroporation efficiency. These electrodes could therefore be useful for PEF application in ROS-sensitive tissues, as well as for disentangling the effect of PEFs on cells from the metabolic impact of electrolytic events arising from the electrode material.

The combination of Ca

The combination of Ca2+ ions and electroporation has gained attention as potential alternative to electrochemotherapy. Ca2+ is an important component of the cell membrane repair system and its presence directly influences the dynamics of the pore cycle after electroporation which can be exploited for cancer therapies. Here, the influence of Ca2+ concentration is investigated on small molecule electrotransfer and release of Calcein from 4T1, MX-1, B16F10, U87 cancer cells after cell exposure to microsecond electric pulses. Moreover, we investigated simultaneous molecule electrotransfer and intracellular calcium ion influx when media was supplemented with different Ca2+ concentrations. Results show that increased concentrations of calcium ions reduce the electrotransfer of small molecules to different lines of cancer cells as well as the release of Calcein. These effects are related with an enhanced membrane repair mechanism. Overall, we show that the efficiency of molecular electrotransfer can be controlled by regulating Ca2+ concentration in the electroporation medium. For the first time, the cause of cancer cell death in vitro from 1 mM CaCl2 concentrations is related to the irreversible loss of Ca2+ homeostasis after cell electroporation. Our findings provide fundamental insight on the mechanisms of Ca2+ electroporation that might lead to improved therapeutic outcomes.

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.This research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.

We demonstrate the ability to excite atoms at well-defined, programmable locations in a magneto-optical trap, either to the continuum (ionisation), or to a Rydberg state. To this end, excitation laser light is shaped into arbitrary intensity patterns with a spatial light modulator. These optical patterns are sensitive to aberrations of the phase of the light field, occuring while traversing the optical beamline. These aberrations are characterised and corrected without observing the actual light field in the vacuum chamber., 5 pages, 5 figures

A.L.R. acknowledges support from the Whitaker International Scholars Program and the European Commission’s Horizon 2020 Marie Sklodowska-Curie Individual Fellowship BRAIN CAMO (No. 797506). G.D. acknowledges support from the European Commission through the project of OrgBIO-ITN 607896.