Objective. A number of tissue penetrating opto-electrodes to simultaneously record and optogenetically influence brain activity have been developed. For experiments at the surface of the brain, such as electrocorticogram (ECoG) recordings and surface optogenetics, fewer devices have been described and no device has found widespread adoption for neuroscientific experiments. One issue slowing adoption is the complexity and fragility of existing devices, typically based on transparent electrode materials like graphene and indium-tin oxide (ITO). We focused here on improving existing processes based on metal traces and polyimide (PI), which produce more robust and cost-effective devices, to develop a multi-electrode array for optophysiology. Approach. The most widely used substrate material for surface electrodes, PI, has seen little use for optophysiologicalμECoG/ECoG arrays. This is due to its lack of transparency at optogenetically relevant short wavelengths. Here we use very thin layers of PI in combination with chrome-gold-platinum electrodes to achieve the necessary substrate transparency and high mechanical flexibility in a device that still rejects light artifacts well. Main results. The manufactured surface arrays have a thickness of only 6.5 µm, resulting in 80% transparency for blue light. We demonstrate immunity against opto-electric artifacts, long term stability and biocompatibility as well as suitability for optical voltage imaging. The biocompatible arrays are capable of recording stable ECoGs over months without any measurable degradation and can be used to map the tonotopic organization of the curved rodent auditory cortex. Significance. Our novel probes combine proven materials and processing steps to create optically near-transparent electrode arrays with superior longevity. In contrast to previous opto-electrodes, our probes are simple to manufacture, robust, offer long-term stability, and are a practical engineering solution for optophysiological experiments not requiring transparency of the electrode sites themselves.

Recording from single neurons in the brain for long periods of time has been a central goal in both basic neuroscience and translational neurology, in order to understand mechanisms underlying brain processes such as learning and to understand the pathogenesis of neurodynamic disease states 1 . Recent advances in materials engineering, digital signal acquisition, and analysis algorithms have brought us closer to achieving this goal, and the possibility has gathered much public attention 2,3 . However, it remains a challenge to record from the same units for weeks to months. Here, we record many high-quality tetrode neuronal signals reliably over long periods of time in both deep and superficial areas of the brain. We achieve this by combining electrochemical roughening and carbon nanotube coating of a flexible platinum/iridium substrate, with materials, packaging, and insertion optimized to minimize tip movement with brain pulsation. This “Magdeburger” probe enables recordings with long-term signal stability and high signal-to-noise ratio at a reasonable cost in both rodent brains and in substantially larger primate brains. Robust tetrode tracking of identified neurons over longer time periods, in multiple independently targeted areas of the brain, will allow fundamental advances in the study of cognitive learning, aging, and pathogenesis, and opens new possibilities for brain interfaces in humans.

The aim of this work is to test and evaluate Poly -(3,4-ethylenedioxythiophene) - poly (styrenesulfonate), simply known by the abbreviation PEDOT:PSS as a possible low cost and transparent electrically conducting polymer for the fabrication of magnetic resonance imaging (MRI) compatible brain stimulation electrodes. During the preliminary testing, the fabricated PEDOT:PSS structures with Polyimide as base layer created no artefacts under MR as well as X-Ray imaging. Additionally, as the thickness of the tested PEDOT:PSS structure was increased from 390nm to approximately 5.80μm by depositing additional material layers, the measured average electrical resistance decreased from 184KΩ to 25.37KΩ.The conventional metal-based electrodes hinder the use of MR or optical imaging during electrophysiological neuroscientific investigations of the brain. Therefore, a hybrid brain stimulation cum recording electrode array fabricated using polyimide as base material and PEDOT:PSS as the transparent electrically conducting material opens the possibility of electrically stimulating brain while simultaneously reaping the benefits of the MR imaging or the optical imaging (e.g. calcium imaging, two-photon microscopy, etc.).

Recent developments in the field of neuroprosthetics have created a demand for cost-effective advanced bonding techniques to mount polymer-based, thin-film, multi-electrode arrays onto PCBs. Low thicknesses of polymer substrates present challenges for common packaging technologies. Here we implemented a cost-effective direct bonding process of polyimide thin-film electrode arrays using vapor phase soldering. Our polymer foil is composed of PI-2611 and contains embedded gold/platinum/chromium traces. Contact pads are platinum coated and no under bump metallization is required. Instead of using wire bonding techniques, the contact pads are flip-chip bonded directly onto the PCB using a lead free solder paste. Transfer of the foil is carried out by vacuum placement. Soldering is subsequently performed in a vapor phase soldering oven. In contrast to wire bonding on flexible substrate materials, vapor phase soldering results in enhanced contact yield of approximately 99%. The landing area of the thin-film electrode, containing the soldered contact pads, is then passivated with a low-shrinkage epoxy in a pin-transfer process. Using such a low-shrinkage material is paramount to achieve sufficient long-term stability of the solder connections and to stabilize the thin polyimide substrate.

Event Abstract Back to Event A 3D-Capable, Flexible, Hybrid µECoG Optrode Martin Deckert1*, Michael T. Lippert2, Kentaroh Takagaki3, Andreas Brose4, Sanchit Rathi5, Bertram Schmidt6 and Frank W. Ohl3 1 Otto-von-Guericke University of Magdeburg, Institute of Micro and Sensor Systems, Germany 2 Leibniz Institute for Neurobiology Magdeburg, Department Systems Physiology, Germany 3 Leibniz Institute for Neurobiology Magdeburgt, Department Systems Physiology, Germany 4 Otto-von-Guericke-University Magdeburg, Institute of Micro and Sensor Systems, Germany 5 Otto von Guericke University Magdeburg, Institute of Micro and Sensor Systems, Germany 6 Otto-von-Guerricke-University Magdeburg, Institute of Micro and Sensor Systems, Germany I. MOTIVATION Extracellular recordings at the mesoscopic scale are of great interdisciplinary interest for basic and clinical neuroscience as well as for brain-machine-interfaces [1-3]. Recent developments in the field of optogenetics have created a demand for advanced engineering tools to not only record neuronal activity, but stimulate it using light [4-5]. II. MATERIALS AND METHODS Here we present a 3D-capable µECoG optrode array for simultaneous electrophysiological recording and optical stimulation in rodents. The array is based on a polyimide substrate (PI-2611, HD MicroSystems) embedding sputtered metallic traces and electrodes. The metal layer is lithographically patterned in a lift-off process to form a 450 nm thick chromium/gold/platinum thin film and encompasses 32 electrode sites (Fig. A) with their respective connecting traces and contact landing pads (Fig. D). The resulting array has a thickness of only 8.5 µm, which makes it optically near transparent and highly flexible. Electrode sites are 50 µm in diameter and were manufactured with spacings from 250 µm to 1 mm. On the backside of the array, 50 µm thick SMD µLEDs (190 x 190 µm², C470UT190-0314-31, Cree) are mounted, delivering distinct optical stimulation (Fig. F, G, I-K). The LEDs are hermetically sealed by a 2 µm and pinhole free CVD deposited parylene C coating by Specialty Coating Systems (SCS). To contact the electrode array onto a PCB harboring a fine-pitch connector, flip-chip bonding and vapor phase soldering was used (Figure B-D, K). The LEDs were contacted via aerosol jet direct writing (Optomec AJ 300 system). III. RESULTS The resulting electrode array is distinguished by typical impedances of 225.8 ± 5.2 kΩ at 1 kHz, sufficient for neural recordings. We successfully tested it in gerbil (Meriones unguiculatus) and rat (Rattus norvegicus, Fig. L-O). Sample traces from gerbil visual cortex are shown in Figure R. Owing to its low thickness, the array was sufficiently transparent (transmittance: 93% at 470 nm measured with TE Cooled CCD spectroscope, Edmund Optics) to allow optogenetic stimulation from the rear-mounted LEDs (Figure Q), and thus effectively forming a read-write neural interface. As apparent in Figure R, stimulation artifacts accompany LED switching. Over the course of a two-month chronic implantation in rats, we found no signs of neural degeneration around the polymer or electrode structures (Figure O). IV. DISCUSSION We successfully developed a thin-film optrode array for application in rodent cortex. It was able to record ongoing LFP in gerbil and rat cortex and emit 10 mW of blue light for optogenetic stimulation. Currently, the optogenetic response is difficult to isolate from the capacitive stimulation artifact, which we plan to reduce further through charge balanced drivers, co-axial shielding and signal processing. V. CONCLUSION A highly flexible µECoG optrode array based on a PI sandwich structure and rear-mounted SMD LEDs was developed. The array is able to record and stimulate at the mesoscopic scale in rodent neocortex, while simultaneous recording and stimulation is still limited by stimulation artifacts. REFERENCES [1] M. E. J. Obien, K. Deligkaris, T. Bullmann, D. J. Bakkum, and U. Frey, “Revealing neuronal function through microelectrode array recordings,” Frontiers in Neuroscience, vol. 8, pp. 1-30, Jan. 2015. [2] J. Ordonez, M. Schuettler, C. Boehler, T. Boretius, and T. Stieglitz, “Thin films and microelectrode arrays for neuroprosthetics,” MRS Bulletin, vol. 37, pp. 590-598, June 2012. [3] G. Buzsáki, C. A. Anastassiou, and C. Koch, “The origin of extracellular fields and currents – EEG, ECoG, LFP and spikes,” Nature Reviews Neuroscience, vol. 13, pp. 407-420, June 2012. [4] K. Y. Kwon, H.-M. Lee, M. Ghovanloo, A. Weber, and W. Li, “Design, fabrication, and packaging of an integrated, wirelessly-powerded optrode array for optogenetics application,” Frontiers in Systems Neuroscience, vol. 9, article 69 (pp. 1-12), May 2015. [5] R. Pashaie, P. Anikeeva, J. H. Lee, R. Prakash, O. Yizhar, M. Prigge, D. Chander, T. J. Richer, and J. Williams, “Optogenetic Brain Interfaces,” IEEE Reviews in Biomedical Engineering, vol. 7, pp. 1-30, April 2014. FIGURE LEGEND (A) 3D-capable µECoG-MEA portfolio. (B) 1st generation flip-chip bonding onto customized PCBs with isotropic conductive adhesive (ICA) via pin transfer of H20E-FC, Epotec. (C, D) 2nd generation flip-chip bonding by stencil printing of lead free solder paste SAC305 from Heraeus and a vapor phase soldering process [overall yield 97%]. (E) Impedance spectroscopy measured in 0.9% NaCl for different packaging techniques. (F) Model of optrode backside with surface mounted µLEDs. (G) Aerosol jet (AJ) directly written conductive paths utilizing ultrasonic atomization (US) of silver ink AG25TE from UT Dots for µLEDs contact. Low stress Ag25TE curing is achieved at 200°C for 1 h in nitrogen atmosphere. (H) Characterization of ICA bump printing manufactured by pneumatic AJ deposition of epoxy E8074 from Acura. (I) Optical microscope image of as-fabricated optrode without passivation, whereas EP 601-LV from Polytec is deployed to be the µLED underfiller and µLED top contact is accomplished by US AJ deposition and curing of E8074. (J) Back side contact by US AJ direct writing of E8074 and curing at 200°C for 1 h in vacuum atmosphere. (K) Parylene C passivated optrode: side view. (L-O) In-vivo chronic implantation and long term stability test in rats over a period of two month. (P) Functional demonstration of optrode on agar phantom. (Q) Optogenetic mesoscopic stimulation in a rodent cortex and simultaneous electrophysiological recording using the hybrid µECoG optrode. (R) Ongoing LFP and reaction to optogenetic stimulation in gerbil neocortex. Figure 1 Acknowledgements The work has been funded by the Priority Program 1665 of the DFG with the support code “DFG/OH 69/1-1” and by the BMBF in the framework of Forschungscampus STIMULATE with the support code “03FO16102A” as well as by the state of Saxony-Anhalt (sup. code “I 60”). Keywords: stimulation, electrocorticography, packaging, MEMS, optrode Conference: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016. Presentation Type: Poster Presentation Topic: MEA Meeting 2016 Citation: Deckert M, Lippert MT, Takagaki K, Brose A, Rathi S, Schmidt B and Ohl FW (2016). A 3D-Capable, Flexible, Hybrid µECoG Optrode. Front. Neurosci. Conference Abstract: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays. doi: 10.3389/conf.fnins.2016.93.00125 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2016; Published Online: 24 Jun 2016. * Correspondence: Dr. Martin Deckert, Otto-von-Guericke University of Magdeburg, Institute of Micro and Sensor Systems, Magdeburg, Germany, martin.deckert@ovgu.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Martin Deckert Michael T Lippert Kentaroh Takagaki Andreas Brose Sanchit Rathi Bertram Schmidt Frank W Ohl Google Martin Deckert Michael T Lippert Kentaroh Takagaki Andreas Brose Sanchit Rathi Bertram Schmidt Frank W Ohl Google Scholar Martin Deckert Michael T Lippert Kentaroh Takagaki Andreas Brose Sanchit Rathi Bertram Schmidt Frank W Ohl PubMed Martin Deckert Michael T Lippert Kentaroh Takagaki Andreas Brose Sanchit Rathi Bertram Schmidt Frank W Ohl Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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The microfabrication and packaging of novel, three-dimensional, polyimide-based, highly flexible, microscale electrocorticography multi-electrode arrays for enhanced epicortical recording of local field potentials is presented. A polyimide foil embeds metallic structures relating to 32 taper-type electrode sites, contact pads as well as interconnecting conductor paths which are integrated in the planar portion of the electrode substrate material. Circular exposed and, thus, active electrode sites are 50 μm in diameter and employed center-to-center pitches range from 250 μm to 1 mm, respectively. As-fabricated 3D-μECoG-MEAs provide taper heights of approximately 4 μm as well as 59 μm being distinguished by characteristic impedances of about 368.9 kΩ at 1 kHz measured in saline electrolyte. The applied packaging strategies favor flip-chip bonding and vapor phase soldering of the polymer substrates to customized printed circuit boards.

The main aim of the proposed work is to review and develop a theoretical background for analysis of different types of neuromodulation techniques. Neuromodulation is a clinical therapeutic tool to modify the neuronal activities in order to address the disorders associated with the nervous system. The most recent development in neuromodulation tools is optogenetics. Being a form of gene therapy, optogenetics combines genetic engineering with optics as stimulation as well as inhibition to observe and control the function of genetically targeted groups of cells with light, often in intact animals.

Open MR scanners with an improved patient access are well-suited for minimal-invasive interventions. Considering that instruments like catheters appear hypointense in the MR image due to their signal-loss artefact, suitable visualization techniques like passive resonant circuits tuned to the Larmor frequency are required for generating a hyperintense change of the signal intensity. Within this paper various microsystems technologies for fabricating resonant markers will be compared in order to estimate their potential for a subsequent application.

The technology of hot embossing is an established process for many years in the realization of electrical and optical conductors. The ability of this method is the realization of robust and reliable structures. In connection with the studies presented here, these skills are applied to the three-dimensional shape of a catheter or other instruments in the field of medical imaging. We generate as an example resonant circuits with the hot embossing technology. The use of hot-embossing technology improves the mechanical stability of the electrical conductor of the resonant circuits through the improved anchoring of the realized structures. The structural resolution is less than 100 microns and the structure height up to 1000 microns with very good reproducibility. The idea for the use of hot embossing is here pursued in two directions. Firstly, for the creation of channels that will later be functionalized by the addition of metal fillers to electrical conductors. For this solution we fill the embossed structures with polymer thick film paste materials. On the other hand, the known from the 3D-MID technology equipment will be used to emboss foil to create three-dimensional structures. As third way we use a classical FPC and laminate this to the surface of the three-dimensional shape with the help of hot embossing technology. All different solution ways will be characterized electrically with the needed values and their visibility in MR image process. The focus of the work, however, lies in the improvement of the mechanical properties of the resonant circuit. Due to the possibilities of the hot embossing technology we can transfer the ideas to other instruments and tools in the medical image processing. A final testing with accelerated temperature storage will be give a detailed answer to the mechanical behavior, because all tools are used under difficult conditions.