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Adam Williamson, Marc Ferro, Pierre Leleux, Esma Ismailova, Attila Kaszas, Thomas Doublet, Pascale Quilichini, Jonathan Rivnay, Balázs Rózsa, Gergely Katona, Christophe Bernard,* and George G. Malliaras* The development of new tools to interface with neural networks provides the key for understanding how the brain works. This is part of the most important fundamental endeavor of neuroscience, namely the creation of new technologies to improve the lives of people suffering from neurological conditions including epilepsy and Parkinson’s disease. Over the past decade, the use of organic electronic devices to interface with the biological world has received a great deal of attention and bloomed into a field now called “organic bioelectronics”.[1,2] A prominent example is the organic electrochemical transistor (OECT), which was recently shown to outperform electrodes in recording local field potentials generated by populations of neurons in the brain.[3] In order to advance future brain–machine interfaces, these devices must also be able to stimulate individual neurons, and do so in a minimally invasive manner. Here, we report microfabricated organic electrochemical transistors embedded in a 4 µm thick parylene film, eliciting minimal glial scarring after 1 month in the brain. The transistors can be placed in a target region of the brain using an insertion shuttle from which they delaminate after implantation. We show that current pulses can be injected from the transistor

Dr. A. Williamson, Dr. A. Kaszas, Dr. T. Doublet, Dr. P. Quilichini, Dr. C. Bernard Aix Marseille Université INS, 13005 Marseille, France, Inserm UMR_S 1106, 13005 Marseille, France E-mail: [email protected] M. Ferro, Dr. P. Leleux, Dr. E. Ismailova, Dr. J. Rivnay, Prof. G. G. Malliaras Department of Bioelectronics Ecole Nationale Supérieure des Mines CMP-EMSE, MOC 13541 Gardanne, France E-mail: [email protected] Dr. P. Leleux Microvitae Technologies Hôtel Technologique Europarc Sainte Victoire Bât 6 Route de Valbrillant 13590 Meyreuil, France Dr. B. Rózsa, Dr. G. Katona Institute of Experimental Medicine Hungarian Academy of Sciences Szigony Str. 43, H-1083 Budapest, Hungary Dr. B. Rózsa The Faculty of Information Technology and Bionics Pázmány Péter Catholic University Prater Str. 50, H-1083 Budapest, Hungary

DOI: 10.1002/adma.201500218

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Localized Neuron Stimulation with Organic Electrochemical Transistors on Delaminating Depth Probes

channel to the hippocampus to stimulate targeted populations of neurons with no degradation in transistor performance. In addition, neurons located as close as 20 µm from the transistor were not affected by the drain current flowing in the channel under recording conditions. We have previously reported the fabrication of the OECTs.[3] This communication introduces their new application as local neural network stimulators and their new delivery method based on noninvasive delaminating probes. Our results demonstrate that OECTs can, in principle, be used in place of passive electrodes in all aspects of basic research and clinical use, with improved performance and more seamless interfacing between electronics and the brain. Interfacing with individual neurons for stimulation involves placing OECTs on penetrating probes and implanting them inside the brain to reach specific areas. Present state-of-the-art electrodes for stimulation are made of relatively thick silicon to guarantee that the probe does not flex and deviate from the calculated implantation trajectory.[4,5] Such rigid probes produce large mechanical forces between the implanted probe and the neural tissue. This produces tissue damage, disrupting neuronal networks, in particular as a result of the inflammatory response triggered by the lesion. When left in place, the probe is detected as a foreign body, triggering further reactions. Astrocytes and microglia begin to effectively insulate the recording interface of the probes from the neuronal tissue.[6] In the case of the glial scar, its development is partially due to the unavoidable tissue damage caused during implantation. However, it is also due to these mechanical forces arising between the implanted probe and the neural tissue.[7] Essentially, the probe is rigidly fixed to the skull, but the brain can make microscale movements, causing forces between the probe and the soft tissue. In order to reduce the immune response of the brain, essentially reducing the amount of inflammation and glial scarring, we utilized a 4 µm thick parylene film with embedded OECTs for our depth probes. In previous work, we showed that despite being so thin, such films have adequate mechanical strength to be self-supporting and to be manipulated by a surgeon for electrocorticography measurements.[8] Although such a thin film represents a significant improvement in reducing the mechanical force with neural tissue, it is not possible to precisely penetrate the surface of the cortex with such a flexible material. A rigid shuttle, ideally as thin as possible to limit damage, is still necessary. As seen in Figure 1, we have developed delaminating depth probes carrying OECTs to enable such precise implantations, while simultaneously reducing mechanical force and limiting

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Figure 1. Schematic of the OECT probe and corresponding histology. a) Layout of the parylene-part of the probe (the embedded transitor). b) Layout of the entire probe showing the parylene- and the shuttle-parts (top panel), corresponding optical micrograph (bottom panel), and principle of delamination (right panel). c) Histology showing the absence of a noticeable glial scar after a one month long implantation in the rat neocortex. The sections were stained with cresyl violet and the arrows show the track of the probe. “Cx” stands for cortex. Scale bar is 250 µm (50 µm in the inset). Additional comparison of the glial scarring around a d) standard silicon probe and e) delaminating depth probe, both implanted for 1 month. Notice the large tissue activation around the silicon probe’s track and negligible activation for the delaminating probe's track (black arrows indicate example glial cell bodies). These sections were stained with anti-glial fibrillary acidic protein. Scale bar is 50 µm.

tissue damage. The probes consist of an SU-8 shuttle which is 5.3 mm in length from base to tip, 200 µm wide, and 40 µm thick. On it is mounted a flexible 4 µm thick parylene film that delaminates from the shuttle after insertion. Each probe has three OECTs, as seen in Figure 1a and b, embedded in the mechanically neutral plane of the parylene film, with a poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) channel, individually addressable source and drain contacts, and an adjacent electrode, also made of PEDOT:PSS. The latter can be used as a local gate for each transistor, as a sink for stimulation currents, or as a simple recording or stimulation electrode. A schematic of the parylene-part of the probe is shown in Figure 1a. The PEDOT:PSS island on the OECT had an area of 15 × 10 µm2, defining a channel with width of 10 µm and length of 5 µm, while allowing sufficient overlap with the source and drain electrodes. The PEDOT:PSS electrode was square, with a side of 13 µm. In both cases, the PEDOT:PSS film thickness was 100 nm. The parylene film is only weakly adhered to the shuttle by van der Waals forces, and the small changes caused by absorbed water from the cerebrospinal fluid (CSF) are enough to completely separate it from the shuttle, as seen schematically in Figure 1b. The shuttle can then be removed, leaving only the 4 µm parylene film with the embedded organic transistors in the tissue. It was verified that the process of delamination did not affect the electrical characteristics of the transistors. A probe was implanted in the cortex of a rat and remained there for 1 month while the rat was permitted to freely move. Figure 1c,e shows no noticeable glial

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scar formation around the probe, consistent with the use of thin organic materials. Contrary to traditional electrolyte-gated field-effect transistors, in which a physical barrier in the form of an oxide or a nitride separates ionic charge in the electrolyte from electronic charge in the channel,[9] OECTs leverage ion transport across the electrolyte/channel interface as part of their mechanism of operation.[10] The lack of a physical barrier at the interface with the electrolyte creates the opportunity to use the conducting polymer channel as a current source for electrical stimulation, rendering the transistor a bidirectional neural interfacing device. Conducting polymers are known to make efficient stimulation electrodes due to their high capacitance,[11] and the same principle should operate with the channel of OECTs. To test this hypothesis, we measured the electrochemical impedance of an OECT and correlated the results with its stimulation characteristics. For this experiment, we used an OECT made of a PEDOT:PSS film with an area of 50 × 20 µm2 and thickness around 700 nm, in order to be able to capture the voltage transient accurately with equipment available in our laboratory. Figure 2 shows that the impedance of the OECT channel, measured in vitro, in an electrolyte, can be modeled by a standard equivalent circuit consisting of a capacitor C, in parallel with a resistor Rp and all in series with a resistor Rs. Cp was found to be 22 nF, which corresponds to an equivalent capacitance per unit area of 2200 µF cm−2. This value is 440× larger than that of the double layer capacitance (≈5 µF cm−2),[12] consistent with volume-charging of the PEDOT:PSS channel.

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Time Time (ms) (ms) Figure 2. Electrical properties of OECT probes. a) Bode plot showing the magnitude of impedance versus frequency for a PEDOT:PSS OECT. The red line is a fit to the R(R//C) circuit shown in the inset. b) Voltage transient (black line) recorded in response to an applied current pulse (blue dashed line) between the channel of an OECT and a gate electrode. The red dashed line corresponds to the theoretical response of the R(R//C) circuit with the values of R and C extracted from the impedance measurement of the same transistor.

A high capacitance is important for stimulation. It can be shown that when an electrode is excited by a current pulse of magnitude i, its response consists of an immediate voltage that is equal to i·Rs and hence follows the shape of the current pulse, together with an “overshoot” voltage that is equal to i·t/C, where t is time.[13] This overshoot voltage, which corresponds to the charging of the interfacial capacitance, can cause undesired electrochemical reactions at the electrode interface. A large capacitance helps minimize this issue. Figure 2b shows that these ideas also apply to OECTs. A transistor was immersed in an electrolyte and a current pulse was applied between its channel (by connecting together the source and drain electrodes) and an Ag/AgCl gate electrode. The obtained voltage response consisted of an instantaneous component, together with a component that increased proportionally with time. The red line corresponds to the transient response of an R(R//C) model, using the parameters extracted from impedance measurements of the same OECT channel. The similarity of the measured and predicted responses shows that an OECT channel behaves as a high

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capacitance electrode, and is therefore suitable for stimulation of neurons. OECTs were subsequently tested in complete extracted hippocampus preparations. This preparation maintains the whole 3D hippocampal architecture, preserving cellular and axonal integrity.[14,15] As seen in Figure 3, we targeted the Schaffer collaterals originating from CA3 pyramidal cells, designated by the colored squares, since their stimulation leads to wellknown responses in the CA1 region, designated by the corresponding colored regions. A recording electrode was placed in the stratum pyramidale of the rightmost section of CA1 along the transverse axis of the hippocampus. Spontaneous oscillations (0.5–2 Hz) can be recorded in the intact hippocampus in physiological conditions.[16] During these oscillations, individual action potentials were resolved by the recording electrode. A probe was implanted in the pyramidal layer to activate CA3 pyramidal cells, and thus Schaffer collaterals, starting in the leftmost section of CA3 along the transverse axis. Monophasic current pulses, ranging between 20 and 40 µA and 20 and 40 µs, were sourced from the channel of an OECT, using the adjacent electrode as a local sink, as seen in Figure 3. We found that this configuration provides the most local stimulation possible, in contrast to a sink placed far away, that would let the current transverse numerous neural networks, activating an uncontrolled number of pathways. Pulses applied from OECTs implanted at sites 1 and 2 did not evoke responses, while pulses applied from OECTs implanted at site 3 systematically evoked network and single cell responses, seen in Figure 3. They were evoked, and not spontaneous, since they occurred for each stimulus in the train. The amplitude of the field response decreased with the number of stimulations, consistent with the known short-term depression that occurs at Schaffer collateral synapses upon repeated activation.[17] This protocol shows that the stimulation was indeed targeted and local, as only pyramidal neurons of the rightmost region of the stimulated CA3 resulted in correspondingly evoked activity in pyramidal neurons of the rightmost region of the CA1, in keeping with the projection zone of CA3 to CA1.[18] The applied stimulation did not cross-stimulate other regions of the CA3, it remained in one targeted region of the CA3, evoking response in one local region of the CA1. Electrical stimulation creates an electric field which directly depolarizes the neuronal membrane, usually at the initial segment of the axon, thus generating an action potential.[19] In order to assess how many neurons can be stimulated using the OECT, we used 3D two-photon imaging[20] of the intact hippocampus implanted with a probe (Figure 4a). This method allows the direct visualization of excited neurons. To assist the two-photon imaging and probe placement in the hippocampus, we used transgenic GIN mice, in which somatostatin-containing interneurons express the marker, green fluorescent protein. The hippocampal tissue was loaded with SR-101 and OGB1-AM, which allow the separation of glial cells from neurons and their Ca2+ imaging, respectively. In Figure 4a, both glial cells (SR-101), and neurons (OGB1-AM), with pyramidal neurons are clearly visible 20 µm directly above the channel of the OECT. Figure 4b shows that single pulses or trains of stimulations consistently evoke a rise in intracellular calcium in imaged neurons. The calcium response is due to the firing

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Figure 3. Stimulating pyramidal neurons in intact hippocampal preparations. a) Pyramidal neurons were recorded from the rightmost section of CA1 along the transverse axis of the hippocampus (dark blue). Correspondingly, pyramidal neurons were stimulated using the OECT, as shown, starting from the leftmost section of CA3 (lightest blue to dark blue) along the transverse axis of the hippocampus. Only stimulation from the rightmost section of CA3 (at site 3) resulted in evoked activity. b) Recorded multiunit response during stimulation at sites 1, 2, and 3. Physiological activity is only evoked when stimulation is applied at site 3. Both population spikes and action potentials are evoked between stimulus pulses. The five pulses recorded in all three traces are the typical stimulation artefacts. c) Selected action potential from stimulation at site 3.

of action potentials.[21] With the two-photon system used here, we can recreate a 3D image of the individual neurons stimulated directly above the OECT. In Figure 4c, we see in the right panels the normalized fluorescence values for individual neurons, the left panels are for reference. The OECT is located at the center of the XY-plane, with each sphere corresponding to the center of 1 of the 135 identified individual neuronal somas. Moving in the z-direction, the closest stimulated neurons are located less than 20 µm above the OECT, and the furthest stimulated neurons are not more than 250 µm above the OECT. These results, in combination with the results of Figure 3b, show that the stimulation provided by the OECT remains very local, not exiting neuronal networks more than 300 µm away from the device. Only these excited networks, via their natural biological connectivity, propagate the excitation to networks located further away. It should also be mentioned that, in addition to monitoring neuronal activity during OECT stimulation, calcium imaging can monitor neuronal activity directly above the device during normal transistor operation. A drain current of 900 µA through the transistor channel, corresponding to a drain voltage of 0.6 V, results in no measurable evoked activity from neurons directly

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above the channel (neurons within 20 µm of the channel). This means that when the transistor is in recording mode, it does not disturb the extracellular environment in any way, even though the channel is in direct contact with the extracellular fluid. In this work, we described the application of OECTs on depth probes, yielding devices capable of penetrating the cortex and stimulating neurons. The probes featured a mechanical delamination process which left inside the brain the transistors embedded in a film that was only 4 µm thick, thus considerably reducing probe invasiveness. The ability of the OECTs to deliver targeted stimulation to a specific local population of neurons was demonstrated by using a specific stimulation framework, ensuring that the corresponding biological response was recorded in a separate local population of neurons. Evoked intracellular calcium levels of pyramidal neurons above the transistor channel correlated directly to the applied stimuli. The results shown here, coupled with the ability of OECTs to provide recordings with a high signal-to-noise ratio, pave the way for the application of OECTs in a variety of research and clinical settings as novel, high performance and minimally invasive devices for in vivo electrophysiology. Future work will focus

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COMMUNICATION Figure 4. Two-photon image of the OECT probe implanted directly beneath the soma of pyramidal neurons in an intact hippocampus preparation. a) The neurons seen in green (OGB1-AM) and glial cells seen in red (SR-101) are located 20 µm above the transistor channel. b) Averaged change in fluorescence in neurons following stimulation, corresponding to a rise in intracellular calcium due to the genesis of action potentials. The blue trace is the average response to a 10 Hz pulse train, the red trace is the average response to single pulses. c) XY-plane image of the implanted probe (left panels) and the corresponding fluorescence profile of the surrounding neuronal population (right panels), before (top) and during (bottom) stimulation. Each sphere is the center of 1 of the 135 identified individual neuronal soma above the OECTs.

on the integration of organic electronic ion pumps for localized drug delivery onto the same depth probes. Such probes would be able to combine electrical recording/stimulation with biochemical stimulation, creating a novel tool for neuroscience research. They will merge the flexibility of lab-on-a-chip style in vitro devices, with the level of neuronal tissue access only provided by in vivo depth probes, essentially creating the era of lab-on-a-probe.

Experimental Section Probe Fabrication: Some of the details of the fabrication of the parylene probes with OECTs have been discussed in previous work.[3] The fabrication process involved the deposition and patterning of parylene-C, gold, and PEDOT:PSS films. Parylene was deposited using an

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SCS Labcoater 2 to a thickness of 2 µm on a glass substrate. These films were patterned using a 4.6 mm thick layer of AZ9260 (MicroChemicals) photoresist and reactive ion etching in an O2 plasma (160 W, 50 sccm O2, and 15 min) using an Oxford 80 plus plasma etcher. Metal pads and interconnects were patterned by a lift-off process. A photoresist, S1813 (Shipley), was spin-coated on the parylene film at 3500 rpm, baked at 110 °C for 60 s, exposed to UV light (150 mJ cm−2) using an SUSS MJB4 contact aligner, and then developed using MF 26 developer. This was followed by the deposition of 5 nm of titanium for adhesion enhancement and 100 nm of gold using a metal evaporator (Alliance Concept EVA450). Lift-off was performed using a 1165 stripper. For the preparation of the PEDOT:PSS films, the formulation of aqueous dispersion (PH 1000 from H.C. Stark) included 5% (v/v) of ethylene glycol, 0.5 µL mL−1 of dodecyl benzene sulfonic acid and 1 wt% of 3-glycidoxypropyltrimethoxysilane, and the resulting dispersion was spun cast at 3000 rpm. The films were subsequently baked at 140 °C for 1 h and were immersed in deionized water to remove any excess low molecular weight compounds. Multiple depositions were used to achieve thicker films. They were patterned using the parylene peel-off

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www.MaterialsViews.com technique.[22] The shuttles were prepared on a separate wafer. A layer of antiadhesive (1% soap solution diluted in distillate water) was first spincoated and dried on a hot plate for 1 min at 110 °C. A 40 micrometers thick layer of SU8-50 (MicroChemicals) was then spin-coated and cured following the recommendations of the manufacturer. The film was then exposed to filtered UV light (SUSS MJB4 contact aligner equipped with 365 nm filter) with a dose of 200 mJ cm−2. Post exposure bake was then performed to complete the crosslinking. The shuttles were then developed and peeled-off form the substrate by immersion in SU8 Developer (MicroChemicals). In Vitro Probe Characterization: Electrochemical impedance spectra were acquired with a potentiostat (Autolab PGSTAT128N) in a three electrode configuration, using platinum and Ag/AgCl as counter and reference electrodes, respectively. 100 × 10−3 M of NaCl in DI water was used as the electrolyte, and the data were analyzed using the associated software. Stimulation profiles were also obtained in the same electrolyte using a current stimulator from Digitimer Ltd. The transient voltage response was measured using an NI PXI-6289 modular instrument. Electrophysiological Recordings in Intact Hippocampal Preparations: All the protocols have been approved by the Institutional Animal Care and Use Committee of INSERM. Electrophysiological recordings were made in the CA1 of the mouse hippocampus. After decapitation of anesthetized male GIN mice (postnatal day 14 to 18), brains were rapidly extracted, and separated into left and right hemispheres. Intact hippocampal preparations were removed from each hemisphere as previously described.[14–16] Each freshly-removed hippocampus preparation was placed in a holding chamber containing oxygenated (95% O2/5% CO2) artificial cerebrospinal fluid (ACSF) (126 × 10−3 M NaCl, 3.5 × 10−3 M KCl, 2 × 10−3 M CaCl2, 1.3 × 10−3 M MgCl2, 1.2 × 10−3 M NaH2PO4, 26.2 × 10−3 M NaHCO3, and 10 × 10−3 M glucose). After 1 h of recovery at room temperature, preparations were transferred to a submerged recording chamber for stimulation and imaging or a submerged chamber for stimulation only, and were continuously perfused with oxygenated ACSF warmed at 33 °C. The probe with OECTs for stimulation was placed in the CA3 region, connected to a current stimulator (Digitimer Ltd). A tungsten electrode (with a tip resistance of 1–3 MΩ) was positioned in the CA1 region of the hippocampus. Recordings were made with a World Precision Instruments DAM80 AC amplifier, and acquired using an analog-to-digital converter (Digidata 1322B or Digidata1440A, Molecular Devices). Analysis was performed using Clampfit (Molecular Devices) and Matlab (Mathworks)-based software. Two Photon Imaging: Multicell loadings of neuronal populations in the intact hippocampus preparations were performed as described previously.[23] Briefly, neurons were stained with Oregon Green BAPTA1 AM (1 × 10−3 M OGB1-AM, Life Technologies), while glial cells could be identified using the astrocytic marker Sulforhodamine-101 (300 × 10−6 M SR-101).[24] Neuronal somata were selected in a 3D space using a cell finder algorithm[20] after acquiring a reference z-stack of the volume on a custom-built 3D fast acousto-optical (3D-AO) trajectory scanning microscope (Femto3D-AO, Femtonics Ltd, Budapest, Hungary) with a femtosecond pulsed laser tuned to 830 nm (Mai Tai HP, SpectraPhysics, Mountain View, CA, USA). The selected neurons were imaged with 33 kHz point−1. The control of imaging and the analysis of data was done using the MES software package (Femtonics Ltd, Budapest, Hungary) based on Matlab (Mathworks). Electrophysiological recording was synchronized to the start of the imaging sessions. All imaging sessions have been conducted with the temperature set to 32 °C. All chemicals and drugs, unless otherwise noted, were purchased from Sigma. Histology: It was carried out according to the protocol described before.[3]

Acknowledgements A.W., A.K., M.F., P.L., and E.I., contributed equally to this work. This work was funded by the European Union’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 602102 (EPITARGET), the A*MIDEX project MIDOE (A_M-AAP-ID-13-24-130531-16.31-BERNARD-HLS), the ANR through

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the project PolyProbe (ANR-13-BSV5-0019-01), the Fondation pour la Recherche Médicale under Grant Agreement No. DBS20131128446, Fondation de l’Avenir, the Region PACA, Orthogonal, Inc., and Microvitae Technologies. A.K. was sponsored by the Fondation pour la Recherche Medicale postdoctoral fellowship under Grant Agreement No. SPF20130526842. J.R. was supported by Marie Curie Postdoctoral Fellowship. The authors thank Gaelle Rondeau and the staff of the clean room at CMP for technical support during the devices fabrication. Finally, A.W. sincerely thanks Robert Charles Williamson for inspiration. Received: January 15, 2015 Revised: April 23, 2015 Published online: June 30, 2015

[1] M. Berggren, A. Richter-Dahlfors, Adv. Mater. 2007, 19, 3201. [2] J. Rivnay, R. M. Owens, G. G. Malliaras, Chem. Mater. 2014, 26, 679. [3] D. Khodagholy, T. Doublet, P. Quilichini, M. Gurfinkel, P. Leleux, A. Ghestem, E. Ismailova, T. Hervé, S. Sanaur, C. Bernard, G. G. Malliaras, Nat. Commun. 2013, 4, 1575. [4] D. A. Henze, Z. Borhegyi, J. Csicsvari, A. Mamiya, K. D. Harris, G. Buzsaki, J. Neurophysiol. 2000, 84, 390. [5] P. Barthó, H. Hirase, L. Monconduit, M. Zugaro, K. D. Harris, G. Buzsáki, J. Neurophysiol. 2004, 92, 600. [6] V. S. Polikov, P. A. Tresco, W. M. Reichert, J. Neurosci. Methods 2005, 148, 1. [7] G. Lind, C. E. Linsmeier, J. Schouenborg, Sci. Rep. 2013, 3, 2942. [8] D. Khodagholy, T. Doublet, M. Gurfinkel, P. Quilichini, E. Ismailova, P. Leleux, T. Herve, S. Sanaur, C. Bernard, G. G. Malliaras, Adv. Mater. 2011, 23, H268. [9] P. Fromherz, in Nanoelectronics and Information Technology (Ed: R. Waser), Wiley-VCH Verlag, Berlin 2003, 781. [10] D. A. Bernards, G. G. Malliaras, Adv. Funct. Mater. 2007, 17, 3538. [11] S. Venkatraman, J. Hendricks, Z. A. King, A. J. Sereno, S. Richardson-Burns, D. Martin, J. M. Carmena, IEEE Trans. Neural Sys. Rehabil. Eng. 2011, 19, 307. [12] S. H. Kim, K. Hong, W. Xie, K. H. Lee, S. Zhang, T. P. Lodge, C. D. Frisbie, Adv. Mater. 2013, 25, 1822. [13] A. J. Bard, L. R. Faulkner, Electrochemical Methods: Fundamentals and Applications, 2nd ed., Wiley, New York, 2000. [14] I. Khalilov, M. Esclapez, I. Medina, D. Aggoun, K. Lamsa, X. Leinekugel, R. Khazipov, Y. Ben-Ari, Neuron 1997, 19, 743. [15] M. L. Davies, S. A. Kirov, R. D. Andrew, J. Neurosci. Methods 2007, 166, 203. [16] R. Goutagny, J. Jackson, S. Williams, Nat. Neurosci. 2009, 12, 1491. [17] D. Debanne, B. H. Gahwiler, S. M. Thompson, J. Physiol. 1998, 507, 237. [18] C. Bernard, H. V. Wheal, Hippocampus 1994, 4, 497. [19] F. Rattay, Neuroscience 1999, 89, 335. [20] G. Katona, G. Szalay, P. Maak, A. Kaszas, M. Veress, D. Hillier, B. Chiovini, E. S. Vizi, B. Roska, B. Rozsa, Nat. Methods 2012, 9, 201. [21] D. S. Greenberg, J. N. D. Kerr, J. Neurosci. Meth. 2009, 176, 1. [22] M. Sessolo, D. Khodagholy, J. Rivnay, F. Maddalena, M. Gleyzes, E. Steidl, B. Buisson, G. G. Malliaras, Adv. Mater. 2013, 25, 2135. [23] C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, Proc. Nat. Acad. Sci. USA 2003, 100, 7319. [24] A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, F. Helmchen, Nat. Methods 2004, 1, 31.

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Adv. Mater. 2015, 27, 4405–4410

Localized Neuron Stimulation with Organic Electrochemical Transistors on Delaminating Depth Probes.

Organic electrochemical transistors are integrated on depth probes to achieve localized electrical stimulation of neurons. The probes feature a mechan...
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