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Glioblastoma is a highly aggressive brain tumor, very invasive and thus difficult to eradicate with standard oncology therapies. Bioelectric treatments based on pulsed electric fields have proven to be a successful method to treat cancerous tissues. However, they rely on stiff electrodes, which cause acute and chronic injuries, especially in soft tissues like the brain. Here we demonstrate the feasibility of delivering pulsed electric fields with flexible electronics using an in ovo vascularized tumor model. We show with fluorescence widefield and multiphoton microscopy that pulsed electric fields induce vasoconstriction of blood vessels and evoke calcium signals in vascularized glioblastoma spheroids stably expressing a genetically encoded fluorescence reporter. Simulations of the electric field delivery are compared with the measured influence of electric field effects on cell membrane integrity in exposed tumor cells. Our results confirm the feasibility of flexible electronics as a means of delivering intense pulsed electric fields to tumors in an intravital 3D vascularized model of human glioblastoma. more...

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Bacterial identification is of first importance in clinic nowadays. For few years, electrochemistry appears as a reliable route for characterizations outside of laboratories. Nowadays, researchers mainly focus on the opportunistic pathogen Pseudomonas aeruginosa because of its production of the Pyocyanin toxin which has an electrochemical case study behavior. Other P. aeruginosa secreted molecules are also studied in a lesser extent. This work deals with the systematic electrochemical characterizations in aprotic and protic solvents of 4 main metabolites of this bacterium in the view of multispecies detection of P. aeruginosa. We report here the behavior of the 2-Heptyl-4(1H)-quinolone (HHQ), Pseudomonas Quinolone Signal (PQS), Pyocyanin (PYO) and the 2′aminoacetophenone (2-AA). All the mentioned species are clearly visible by using electrochemical techniques (cyclic and square wave voltammetries). The 2 most suitable species for electrochemical detection appear to be PQS and PYO because of their detection at low potential. more...

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug-delivery systems. more...

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. more...

© 2018 IOP Publishing Ltd. Objective. Neural electrophysiology is often conducted with traditional, rigid depth probes. The mechanical mismatch between these probes and soft brain tissue is unfavorable for tissue interfacing. Making probes compliant can improve biocompatibility, but as a consequence, they become more difficult to insert into the brain. Therefore, new methods for inserting compliant neural probes must be developed. Approach. Here, we present a new bioresorbable shuttle based on the hydrolytically degradable poly(vinyl alcohol) (PVA) and poly(lactic-co-glycolic acid) (PLGA). We show how to fabricate the PVA/PLGA shuttles on flexible and thin parylene probes. The method consists of PDMS molding used to fabricate a PVA shuttle aligned with the probe and to also impart a sharp tip necessary for piercing brain tissue. The PVA shuttle is then dip-coated with PLGA to create a bi-layered shuttle. Main results. While single layered PVA shuttles are able to penetrate agarose brain models, only limited depths were achieved and repositioning was not possible due to the fast degradation. We demonstrate that a bilayered approach incorporating a slower dissolving PLGA layer prolongs degradation and enables facile insertion for at least several millimeters depth. Impedances of electrodes before and after shuttle preparation were characterized and showed that careful deposition of PLGA is required to maintain low impedance. Facilitated by the shuttles, compliant parylene probes were also successfully implanted into anaesthetized mice and enabled the recording of high quality local field potentials. Significance. This work thereby presents a solution towards addressing a key challenge of implanting compliant neural probes using a two polymer system. PVA and PLGA are polymers with properties ideal for translation: commercially available, biocompatible with FDA-approved uses and bioresorbable. By presenting new ways to implant compliant neural probes, we can begin to fully evaluate their chronic biocompatibility and performance compared to traditional, rigid electronics. more...

The vapor phase polymerization (VPP) technique is used to produce thin films of poly(3,4-ethylenedioxythiopene) (PEDOT) in which the Fe(III)Tosylate oxidant is altered. The oxidant is changed with the addition of an amphiphilic co-polymer having different molecular weights, namely 2800 Da. and 5800 Da. Resulting PEDOT films produce conductivities of ≈1500 and ≈3000 S cm−1 respectively. Small angle X-ray diffraction (SA-XRD) indicates that the oxidant incorporating the larger molecular weight co-polymer possesses ordered structure and that this in turn helps “template” the PEDOT during film formation. The structure and composition of the bottom (i.e. initial film formation) and top (i.e. final film formation) PEDOT surfaces are studied using surface sensitive analytical techniques; small angle X-ray diffraction (SA-XRD), ultraviolet photoelectron spectroscopy (UPS), 2D grazing incidence X-ray diffraction (2D-GIXD), metastable induced electron spectroscopy (MIES) and neutral impact collision ion scattering spectroscopy (NICISS). The results indicate that the increase in conductivity using the larger molecular weight co-polymer additive is due to the film having larger lamella- and π-stacking regions in addition to doping levels which remain unchanged throughout film formation. These conclusions are further supported by results obtained on a model PEDOT:Tosylate system using density functional theory (DFT) calculations Refereed/Peer-reviewed more...

International audience; Inkjet-printed PEDOT:PSS electrodes are shown to record cutaneous electrophysiological signals such as electrocardiograms via a simple finger-to-electrode contact. The recordings are of high quality and show no deterioration over a 3 month period, paving the way for the development of the next generation of low-cost, convenient-to-use healthcare monitoring devices. more...

International audience; Continuous and long-term monitoring of cellular and micro-organ activity is required for new insights intophysiology and novel technologies such as Organs-on-Chip. Moreover, recent advances in stem cell technologyand especially in the field of diabetes call for non-invasive approaches in quality testing of the large quantities ofsurrogate pancreatic islets to be generated. Electrical activity of such a micro-organ results in single cell actionpotentials (APs) of high frequency and in low frequency changes in local field potentials (slow potentials or SPs),reflecting coupled cell activity and overall organ physiology. Each of them is indicative of different physiologicalstages in islet activation. Action potentials in islets are of small amplitude and very difficult to detect. The use ofPEDOT:PSS to coat metal electrodes is expected to reduce noise and results in a frequency-dependent change inimpedance, as shown here. Whereas detection of high-frequency APs improves, low frequency SPs are less welldetected which is, however, an acceptable trade off in view of the strong amplitude of SPs. Using a dedicatedsoftware, recorded APs and SPs can be automatically diagnosed and analyzed. Concomitant capture of the twosignals will considerably increase the diagnostic power of monitoring islets and islet surrogates in fundamentalresearch as well as drug screening or the use of islets as biosensors. more...

Recent applications of organic electrochemical transistors (OECTs) in bioelectronics motivate the search for new materials with mixed electronic and ionic conductivity. We investigate the characteristics of a series of poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials with a new class of anionic polyelectrolytes used as dopants and stabilizers, replacing the traditionally used poly(styrene sulfonate) (PSS). We show that the backbone of the polyanion plays a major role in determining device performance, while its molecular weight and the counter ion used during PEDOT synthesis play a less important role. We find that transconductance increases with the degree of swelling of the film, consistent with enhanced ion transport. Finally, we identify a polymer that offers performance close to the state-of-the-art. This work highlights the importance of the polyanion phase as a means to control OECT performance. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 147–151 more...

Transistors with tunable transconductance allow high-quality recordings of human brain rhythms., Despite recent interest in organic electrochemical transistors (OECTs), sparked by their straightforward fabrication and high performance, the fundamental mechanism behind their operation remains largely unexplored. OECTs use an electrolyte in direct contact with a polymer channel as part of their device structure. Hence, they offer facile integration with biological milieux and are currently used as amplifying transducers for bioelectronics. Ion exchange between electrolyte and channel is believed to take place in OECTs, although the extent of this process and its impact on device characteristics are still unknown. We show that the uptake of ions from an electrolyte into a film of poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) leads to a purely volumetric capacitance of 39 F/cm3. This results in a dependence of the transconductance on channel thickness, a new degree of freedom that we exploit to demonstrate high-quality recordings of human brain rhythms. Our results bring to the forefront a transistor class in which performance can be tuned independently of device footprint and provide guidelines for the design of materials that will lead to state-of-the-art transistor performance. more...

Organic electrochemical transistors are integrated on depth probes to achieve localized electrical stimulation of neurons. The probes feature a mechanical delamination process which leaves only a 4 μm thick film with embedded transistors inside the brain. This considerably reduces probe invasiveness and correspondingly improves future brain-machine interfaces. more...

International audience; Fully printed electrodes consisting of a conducting polymer and an ionic liquid gel are fabricated on a stretchable textile. They are shown to record cardiac activity while the wearer is moving and for long periods of time, paving the way for the development of low-cost devices for continuous health monitoring. more...

Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk. As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (µFIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The γ-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control. As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset. more...

Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques. Funding Agencies|European Research Council (ERC) under the European Union [716867, 949191]; City Council of Brno, Czech Republic; European Research Council [834677]; Swedish Research Council; MedTechLabs more...