Search

Objective. Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation. Approach. We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis. Main results. A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses. Significance. These approaches can enable studies in small animals that were previously challenging, such as long-term in vivo studies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases. Funding Agencies|European Research Council (ERC) under the European Unions Horizon 2020 research and innovation program (EDG Grant) [949191]; city council of Brno, Czech Republic; European Research Council [834677]; Knut and Alice Wallenberg Foundation; Swedish Research Council; MedTechLabs

Optically driven electronic neuromodulation devices are a novel tool in basic research and offer new prospects in medical therapeutic applications. Optimal operation of such devices requires efficient light capture and charge generation, effective electrical communication across the device’s bioelectronic interface, conformal adhesion to the target tissue, and mechanical stability of the device during the lifetime of the implant—all of which can be tuned by spatial structuring of the device. We demonstrate a 3D structured opto-bioelectronic device—an organic electrolytic photocapacitor spatially designed by depositing the active device layers on an inverted micropyramid-shaped substrate. Ultrathin, transparent, and flexible micropyramid-shaped foil was fabricated by chemical vapour deposition of parylene C on silicon moulds containing arrays of inverted micropyramids, followed by a peel-off procedure. The capacitive current delivered by the devices showed a strong dependency on the underlying spatial structure. The device performance was evaluated by numerical modelling. We propose that the developed numerical model can be used as a basis for the design of future functional 3D design of opto-bioelectronic devices and electrodes.

Nongenetic optical control of neurons is a powerful technique to study and manipulate the function of the nervous system. This research has benchmarked the performance of organic electrolytic photocapacitor (OEPC) optoelectronic stimulators at the level of single mammalian cells: human embryonic kidney (HEK) cells with heterologously expressed voltage-gated K+ channels and hippocampal primary neurons. OEPCs act as extracellular stimulation electrodes driven by deep red light. The electrophysiological recordings show that millisecond light stimulation of OEPC shifts conductance-voltage plots of voltage-gated K+ channels by ≈30 mV. Models are described both for understanding the experimental findings at the level of K+ channel kinetics in HEK cells, as well as elucidating interpretation of membrane electrophysiology obtained during stimulation with an electrically floating extracellular photoelectrode. A time-dependent increase in voltage-gated channel conductivity in response to OEPC stimulation is demonstrated. These findings are then carried on to cultured primary hippocampal neurons. It is found that millisecond time-scale optical stimuli trigger repetitive action potentials in these neurons. The findings demonstrate that OEPC devices enable the manipulation of neuronal signaling activities with millisecond precision. OEPCs can therefore be integrated into novel in vitro electrophysiology protocols, and the findings can inspire in vivo applications.

The use of electronic devices in medical care is one of the main targets of precision medicine. The field of bioelectronic medicine uses electronic devices to diagnose or treat diseases and disorde ...

Successful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) “shielding” of residual tumor cells from promising chemotherapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell‐killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 104‐fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically‐driven organic ion pump (“GemIP”) to achieve controlled, targeted Gem delivery to GBM cells. Thus, GemIP‐mediated Gem delivery is confirmed to be temporally and electrically controllable with pmol min−1 precision and electric addressing is linked to the efficient killing of GBM cell monolayers. Most strikingly, GemIP‐mediated GEM delivery leads to the overt disintegration of targeted GBM tumor spheroids. Electrically‐driven chemotherapy, here exemplified, has the potential to radically improve the efficacy of GBM adjuvant chemotherapy by enabling exquisitely‐targeted and controllable delivery of drugs irrespective of whether these can cross the BBB., An electronically‐driven ion pump is engineered for the targeted delivery of the charged chemotherapeutic gemcitabine to brain cancer cells. Delivery of drug ions over a cation exchange membrane at currents in the nanoampere range triggers brain cancer cell death and microtumor disintegration. Local gemcitabine treatment offers a therapeutical window, in contrast to standard treatment.

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.

Implantable clinical neuroelectronic devices are limited by a lack of reliable, safe, and minimally invasive methods to wirelessly modulate neural tissue. Here, we address this challenge by using organic electrolytic photocapacitors (OEPCs) to perform chronic peripheral nerve stimulation via transduction of tissue-penetrating deep-red light into electrical signals. The operating principle of the OEPC relies on efficient charge generation by nanoscale organic semiconductors comprising nontoxic commercial pigments. OEPCs integrated on an ultrathin cuff are implanted, and light impulses at wavelengths in the tissue transparency window are used to stimulate from outside of the body. Typical stimulation parameters involve irradiation with pulses of 50-1000 μs length (638 or 660 nm), capable of actuating the implant about 10 mm below the skin. We detail how to benchmark performance parameters of OEPCs first ex vivo, and in vivo using a rat sciatic nerve. Incorporation of a microfabricated zip-tie mechanism enabled stable, long-term nerve implantation of OEPC devices in rats, with sustained ability to non-invasively mediate neurostimulation over 100 days. OEPC devices introduce a high performance, ultralow volume (0.1 mm3), biocompatible approach to wireless neuromodulation, with potential applicability to an array of clinical bioelectronics.

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., Microfabricated electrochemical devices that precisely control oxygen and hydrogen peroxide gradients for biological experiments are presented.

Article Open Access Published: 30 July 2019 Wireless organic electronic ion pumps driven by photovoltaics Marie Jakešová, Theresia Arbring Sjöström, Vedran Đerek, David Poxson, Magnus Berggren, Eric Daniel Głowacki & Daniel T. Simon npj Flexible Electronics volume 3, Article number: 14 (2019) Cite this article 1676 Accesses 1 Citations 8 Altmetric Metricsdetails Abstract The organic electronic ion pump (OEIP) is an emerging bioelectronic technology for on-demand and local delivery of pharmacologically active species, especially targeting alkali ions, and neurotransmitters. While electrical control is advantageous for providing precise spatial, temporal, and quantitative delivery, traditionally, it necessitates wiring. This complicates implantation. Herein, we demonstrate integration of an OEIP with a photovoltaic driver on a flexible carrier, which can be addressed by red light within the tissue transparency window. Organic thin-film bilayer photovoltaic pixels are arranged in series and/or vertical tandem to provide the 2.5–4.5 V necessary for operating the high- resistance electrophoretic ion pumps. We demonstrate light-stimulated transport of cations, ranging in size from protons to acetylcholine. The device, laminated on top of the skin, can easily be driven with a red LED emitting through a 1.5-cm-thick finger. The end result of our work is a thin and flexible integrated wireless device platform.

Electronics implemented on biocompatible ultrathin substrates like polyethylene terephthalate, polyimide, or parylene enabled a wide range of conformable, lightweight smart wearables and implantables. However, applications in such dynamic environments require robust devices that adjust and stretch while maintaining their functionality. Universal approaches that unite scalable, low-cost fabrication with high performance and versatile, space-efficient design are sparse. Here, stretchable architectures of parylene enabled by Origami-inspired folds at the micrometer scale are demonstrated. Parylene is directly deposited onto anisotropically etched silicon molds to greatly reduce bending stress, allowing folds with bending radii of a few micrometers. 50-nm-thick gold conductors fabricated on the folded parylene facilitate electronics with a stretchability of up to 55% tensile strain. The conductors sustain a resistance below 20 omega during reversible stretching of more than 10 000 cycles, enabling long-term operation in practical settings. This method presents a versatile tool for the microfabrication of stretchable devices with tunable properties. Funding Agencies|European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programEuropean Research Council (ERC) [949191, 757931]; Erasmus+ scholarship program of the European Commission; Croatian Science Foundation [UIP-2019-04-1753]; Knut and Alice Wallenberg Foundation in SwedenKnut & Alice Wallenberg Foundation

Research on semiconductor photocatalysts for the conversion of solar energy into chemical fuels has been at the forefront of renewable energy technologies. Water splitting to produce H2 and CO2 reduction to hydrocarbons are the two prominent approaches. A lesser-known process, the conversion of solar energy into the versatile high-energy product H2O2 via reduction of O2 has been proposed as an alternative concept. Semiconductor photoelectrodes for the direct photosynthesis of H2O2 from O2 have not been applied up to now. Photoelectrocatalytic oxygen reduction to peroxides in aqueous electrolytes by hydrogen-bonded organic semiconductor is observed photoelectrodes. These materials have been found to be remarkably stable operating in a photoelectrochemical cell converting light into H2O2 under constant illumination for at least several days, functioning in a pH range from 1 to 12. This is the first report of a semiconductor photoelectrode for H2O2 production, with catalytic performance exceeding prior reports on photocatalysts by one to two orders of magnitude in terms of peroxide yield/catalyst amount/time. The combination of a strongly reducing conduction band energy level with stability in aqueous electrolytes opens new avenues for this widely available materials class in the field of photo(electro) catalysis.

Organic electronic materials enable a simple optoelectronic device for wireless electrical stimulation of single cells., Optical control of the electrophysiology of single cells can be a powerful tool for biomedical research and technology. Here, we report organic electrolytic photocapacitors (OEPCs), devices that function as extracellular capacitive electrodes for stimulating cells. OEPCs consist of transparent conductor layers covered with a donor-acceptor bilayer of organic photoconductors. This device produces an open-circuit voltage in a physiological solution of 330 mV upon illumination using light in a tissue transparency window of 630 to 660 nm. We have performed electrophysiological recordings on Xenopus laevis oocytes, finding rapid (time constants, 50 μs to 5 ms) photoinduced transient changes in the range of 20 to 110 mV. We measure photoinduced opening of potassium channels, conclusively proving that the OEPC effectively depolarizes the cell membrane. Our results demonstrate that the OEPC can be a versatile nongenetic technique for optical manipulation of electrophysiology and currently represents one of the simplest and most stable and efficient optical stimulation solutions.

Hydrogen peroxide is one of the most important industrial chemicals and there is great demand for the production of H

An efficient nanoscale semiconducting optoelectronic system is reported, which is optimized for neuronal stimulation: the organic electrolytic photocapacitor. The devices comprise a thin (80 nm) trilayer of metal and p-n semiconducting organic nanocrystals. When illuminated in physiological solution, these metal-semiconductor devices charge up, transducing light pulses into localized displacement currents that are strong enough to electrically stimulate neurons with safe light intensities. The devices are freestanding, requiring no wiring or external bias, and are stable in physiological conditions. The semiconductor layers are made using ubiquitous and nontoxic commercial pigments via simple and scalable deposition techniques. It is described how, in physiological media, photovoltage and charging behavior depend on device geometry. To test cell viability and capability of neural stimulation, photostimulation of primary neurons cultured for three weeks on photocapacitor films is shown. Finally, the efficacy of the device is demonstrated by achieving direct optoelectronic stimulation of light-insensitive retinas, proving the potential of this device platform for retinal implant technologies and for stimulation of electrogenic tissues in general. These results substantiate the conclusion that these devices are the first non-Si optoelectronic platform capable of sufficiently large photovoltages and displacement currents to enable true capacitive stimulation of excitable cells.

Low-cost semiconductor photocatalysts offer unique possibilities for industrial chemical transformations and energy conversion applications. We report that a range of organic semiconductors are capable of efficient photocatalytic oxygen reduction to H2O2 in aqueous conditions. These semiconductors, in the form of thin films, support a 2-electron/2-proton redox cycle involving photoreduction of dissolved O-2 to H2O2, with the concurrent photooxidation of organic substrates: formate, oxalate, and phenol. Photochemical oxygen reduction is observed in a pH range from 2 to 12. In cases where valence band energy of the semiconductor is energetically high, autoxidation competes with oxidation of the donors, and thus turnover numbers are low. Materials with deeper valence band energies afford higher stability and also oxidation of H2O to O-2. We found increased H2O2 evolution rate for surfactant-stabilized nanoparticles versus planar thin films. These results evidence that photochemical O-2 reduction may be a widespread feature of organic semiconductors, and open potential avenues for organic semiconductors for catalytic applications. Funding Agencies|Wallenberg Center for Molecular Medicine at Linkoping University; "Aufbruch Bayern" initiative of the state of Bavaria

Successful formation of electronic interfaces between living cells and semiconductors hinges on being able to obtain an extremely close and high surface-area contact, which preserves both cell viability and semiconductor performance. To accomplish this, we introduce organic semiconductor assemblies consisting of a hierarchical arrangement of nanocrystals. These are synthesised via a colloidal chemical route that transforms the nontoxic commercial pigment quinacridone into various biomimetic three-dimensional arrangements of nanocrystals. Through a tuning of parameters such as precursor concentration, ligands and additives, we obtain complex size and shape control at room temperature. We elaborate hedgehog-shaped crystals comprising nanoscale needles or daggers that form intimate interfaces with the cell membrane, minimising the cleft with single cells without apparent detriment to viability. Excitation of such interfaces with light leads to effective cellular photostimulation. We find reversible light-induced conductance changes in ion-selective or temperature-gated channels., Nanomaterials that form a bioelectronic interface with cells are fascinating tools for controlling cellular behavior. Here, the authors photostimulate single cells with spiky assemblies of semiconducting quinacridone nanocrystals, whose nanoscale needles maximize electronic contact with the cells.

Correction for ‘Organic semiconductor perylenetetracarboxylic diimide (PTCDI) electrodes for electrocatalytic reduction of oxygen to hydrogen peroxide’ by Magdalena Warczak et al., Chem. Commun., 2018, 54, 1960–1963.