Bioelektronické materiály a systémy

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    Light-Controlled Electric Stimulation with Organic Electrolytic Photocapacitors Achieves Complex Neuronal Network Activation: Semi-Chronic Study in Cortical Cell Culture and Rat Model
    (Wiley, 2024-08-13) Nowakowska, Marta; Jakešová, Marie; Schmidt, Tony; Opančar, Aleksandar; Polz, Mathias; Reimer, Robert; Fuchs, Julia; Patz, Silke; Ziesel, Daniel; Scheruebel, Susanne; Kornmueller, Karin; Rienmüller, Theresa; Derek, Vedran; Glowacki, Eric Daniel; Schindl, Rainer; Üçal, Muammer
    Neurostimulation employing photoactive organic semiconductors offers an appealing alternative to conventional techniques, enabling targeted action and wireless control through light. In this study, organic electrolytic photocapacitors (OEPC) are employed to investigate the effects of light-controlled electric stimulation on neuronal networks in vitro and in vivo. The interactions between the devices and biological systems are characterized. Stimulation of primary rat cortical neurons results in an elevated expression of c-Fos within a mature neuronal network. OEPC implantation for three weeks and subsequent stimulation of the somatosensory cortex leads to an increase of c-Fos in neurons at the stimulation site and in connected brain regions (entorhinal cortex, hippocampus), both in the ipsi- and contralateral hemispheres. Reactivity of glial and immune cells after semi-chronic implantation of OEPC in the rat brain is comparable to that of surgical controls, indicating minimal foreign body response. Device functionality is further substantiated through retained charging dynamics following explantation. OEPC-based, light-controlled electric stimulation has a significant impact on neural responsiveness. The absence of detrimental effects on both the brain and device encourages further use of OEPC as cortical implants. These findings highlight its potential as a novel mode of neurostimulation and instigate further exploration into applications in fundamental neuroscience. Wireless cortical stimulation is an attractive alternative to standard neurostimulation methods. Organic photoactive semiconductors can transduce light into electric signal, even in ultrathin layers, which can be used to stimulate neurons. In this study, light-based stimulation activated complex neuronal networks in vitro and in vivo, including deep brain regions. The devices proved safe and stable over three weeks of implantation. image
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    Choosing the right electrode representation for modeling real bioelectronic interfaces: a comprehensive guide
    (IOP Publishing, 2024-08-01) Opančar, Aleksandar; Glowacki, Eric Daniel; Derek, Vedran
    Objective. Producing realistic numerical models of neurostimulation electrodes in contact with the electrolyte and tissue, for use in time-domain finite element method simulations while maintaining a reasonable computational burden remains a challenge. We aim to provide a straightforward experimental-theoretical hybrid approach for common electrode materials (Ti, TiN, ITO, Au, Pt, IrOx) that are relevant to the research field of bioelectronics, along with all the information necessary to replicate our approach in arbitrary geometry for real-life experimental applications. Approach. We used electrochemical impedance spectroscopy (EIS) to extract the electrode parameters in the AC regime under different DC biases. The pulsed electrode response was obtained by fast amperometry (FA) to optimize and verify the previously obtained electrode parameters in a COMSOL Multiphysics model. For optimization of the electrode parameters a constant phase element (CPE) needed to be implemented in time-domain. Main results. We find that the parameters obtained by EIS can be used to accurately simulate pulsed response only close to the electrode open circuit potential, while at other potentials we give corrections to the obtained parameters, based on FA measurements. We also find that for many electrodes (Au, TiN, Pt, and IrOx), it is important to implement a distributed CPE rather than an ideal capacitor for estimating the electrode double-layer capacitance. We outline and provide examples for the novel time-domain implementation of the CPE for finite element method simulations in COMSOL Multiphysics. Significance. An overview of electrode parameters for some common electrode materials can be a valuable and useful tool in numerical bioelectronics models. A provided FEM implementation model can be readily adapted to arbitrary electrode geometries and used for various applications. Finally, the presented methodology for parametrization of electrode materials can be used for any materials of interest which were not covered by this work.
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    Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor
    (Springer Nature, 2021-11-22) Ejneby, Malin Silver; Jakešová, Marie; Ferrero, Jose J.; Migliaccio, Ludovico; Sahalianov, Ihor; Zhao, Zifang; Berggren, Magnus; Khodagholy, Dion; Derek, Vedran; Gelinas, Jennifer N.; Glowacki, Eric Daniel
    Implantable devices for the wireless modulation of neural tissue need to be designed for reliability, safety and reduced invasiveness. Here we report chronic electrical stimulation of the sciatic nerve in rats by an implanted organic electrolytic photocapacitor that transduces deep-red light into electrical signals. The photocapacitor relies on commercially available semiconducting non-toxic pigments and is integrated in a conformable 0.1-mm(3) thin-film cuff. In freely moving rats, fixation of the cuff around the sciatic nerve, 10 mm below the surface of the skin, allowed stimulation (via 50-1,000-mu s pulses of deep-red light at wavelengths of 638 nm or 660 nm) of the nerve for over 100 days. The robustness, biocompatibility, low volume and high-performance characteristics of organic electrolytic photocapacitors may facilitate the wireless chronic stimulation of peripheral nerves. An organic electrolytic photocapacitor transducing deep-red light into electrical signals and implanted within a thin cuff around the sciatic nerve of rats allows for wireless electrical stimulation of the nerve for over 100 days.
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    Faradaic Pixels for Precise Hydrogen Peroxide Delivery to Control M-Type Voltage-Gated Potassium Channels
    (Wiley, 2022-01-01) Abudllaeva, Oliya S.; Sahalianov, Ihor; Ejneby, Malin Silver; Jakešová, Marie; Zozoulenko, Igor; Liin, Sara I.; Glowacki, Eric Daniel
    H2O2 plays a significant role in a range of physiological processes where it performs vital tasks in redox signaling. The sensitivity of many biological pathways to H2O2 opens up a unique direction in the development of bioelectronics devices to control levels of reactive-oxygen species (ROS). Here a microfabricated ROS modulation device that relies on controlled faradaic reactions is presented. A concentric pixel arrangement of a peroxide-evolving cathode surrounded by an anode ring which decomposes the peroxide, resulting in localized peroxide delivery is reported. The conducting polymer (poly(3,4-ethylenedioxythiophene) (PEDOT), is exploited as the cathode. PEDOT selectively catalyzes the oxygen reduction reaction resulting in the production of hydrogen peroxide (H2O2). Using electrochemical and optical assays, combined with modeling, the performance of the devices is benchmarked. The concentric pixels generate tunable gradients of peroxide and oxygen concentrations. The faradaic devices are prototyped by modulating human H2O2-sensitive Kv7.2/7.3 (M-type) channels expressed in a single-cell model (Xenopus laevis oocytes). The Kv7 ion channel family is responsible for regulating neuronal excitability in the heart, brain, and smooth muscles, making it an ideal platform for faradaic ROS stimulation. The results demonstrate the potential of PEDOT to act as an H2O2 delivery system, paving the way to ROS-based organic bioelectronics.
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    State-of-the-Art Electronic Materials for Thin Films in Bioelectronics
    (Wiley, 2023-08-01) Gablech, Imrich; Glowacki, Eric Daniel
    This review is dedicated to electronics materials enabling thin-film-based neural interface and bioelectronics devices. First-generation bioelectronic medicine devices feature hand-crafted bulk interface electrodes, wires and interconnects, and insulators. This review discusses how modern materials science, especially know-how repurposed from semiconductor and microdevice technologies, enables next-generation bioelectronics. Those are divided into two subgroups: second and third generation. The former refers to rigid microscaled devices, while the latter is defined as soft, ultrathin, and flexible microdevices. A critical assessment of different biointerface electrodes, conductors for interconnects, and insulators for substrates, passivation, and encapsulation layers is made. The goal is not to give an exhaustive account of every use-example of given materials, but to point out specific aspects that are relevant to making the right choices for materials for a given device or application. Unique advantages of specific materials are highlighted, while also focusing on weaker points and caveats that those materials may have. The goal is to have an up-to-date handbook for persons entering the field which also points out tips and tricks as well as challenging problems that researchers can be inspired to confront and overcome.