Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Significance statement: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already -established drugs in the fight against hard -to -treat tumors.

Hydrogels are promising materials for medical devices interfacing with neural tissues due to their similar mechanical properties. Traditional hydrogel-based bio-interfaces lack sufficient electrical conductivity, relying on low ionic conductivity, which limits signal transduction distance. Conducting polymer hydrogels offer enhanced ionic and electronic conductivities and biocompatibility but often face challenges in processability and require aggressive polymerization methods. Herein, we demonstrate in situ enzymatic polymerization of pi-conjugated monomers in a hyaluronan (HA)-based hydrogel bioink to create cell-compatible, electrically conductive hydrogel structures. These structures were fabricated using 3D bioprinting of HA-based bioinks loaded with conjugated monomers, followed by enzymatic polymerization via horseradish peroxidase. This process increased the hydrogels' stiffness from about 0.6 to 1.5 kPa and modified their electroactivity. The components and polymerization process were well-tolerated by human primary dermal fibroblasts and PC12 cells. This work presents a novel method to fabricate cytocompatible and conductive hydrogels suitable for bioprinting. These hybrid materials combine tissue-like mechanical properties with mixed ionic and electronic conductivity, providing new ways to use electricity to influence cell behavior in a native-like microenvironment. This study introduces a novel method to enhance hydrogel conductivity and biocompatibility for biomedical applications. By using in situ enzymatic polymerization of pi-conjugated monomers within a hyaluronan-based hydrogel bioink, followed by 3D bioprinting, the resulting hydrogels exhibit improved stiffness, electroactivity, and cytocompatibility. These conductive hydrogels provide a versatile platform for advanced 3D cell culture and neural engineering.image (c) 2024 WILEY-VCH GmbH

Here we propose a strategy to functionalize poly(ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) based organic electrochemical transistors (OECTs) for sensing the inflammatory cytokine interleukin 6 (IL6). For this aim we use diazonium chemistry to couple 4-aminobenzoic acid to sulfonate moieties on the PSS, which can act as anchors for aptamers or other recognition elements (e.g., fluorescent, or redox probes). We investigated this approach with a commercial screen-printable PEDOT:PSS formulation but also studied the effect of PEDOT to PSS ratio as well as the amount of crosslinker in other PEDOT:PSS formulations. For screen printed OECTs, it was possible to distinguish between IL6 and bovine serum albumin (BSA) in buffer solution and detect IL6 when added in bovine plasma in the nanomolar range. Furthermore, functionalization of PEDOT:PSS formulations with higher PSS content (compared to the "standard" solutions used for OECTs) combined with frequency dependent measurements showed the potential to detect IL6 concentrations below 100 pM.

Microbial electrochemical systems (MESs) rely on the microbes' ability to transfer charges from their anaerobic respiratory processes to electrodes through extracellular electron transfer (EET). To increase the generally low output signal in devices, advanced bioelectrical interfaces tend to augment this problem by attaching conducting nanoparticles, such as positively charged multiwalled carbon nanotubes (CNTs), to the base carbon electrode to electrostatically attract the negatively charged bacterial cell membrane. On the other hand, some reports point to the importance of the magnitude of the surface charge of functionalized single-walled CNTs (SWCNTs) as well as the size of functional groups for interaction with the cell membrane, rather than their polarity. To shed light on these phenomena, in this study, we prepared and characterized well-solubilized aqueous dispersions of SWCNTs functionalized by either positively or negatively charged cellulose-derivative polymers, as well as with positively charged or neutral small molecular surfactants, and tested the electrochemical performance of Shewanella oneidensis MR-1 in MESs in the presence of these functionalized SWCNTs. By simple injection into the MESs, the positively charged polymeric SWCNTs attached to the base carbon felt (CF) electrode, and as fluorescence microscopy revealed, allowed bacteria to attach to these structures. As a result, EET currents continuously increased over several days of monitoring, without bacterial growth in the electrolyte. Negatively charged polymeric SWCNTs also resulted in continuously increasing EET currents and a large number of bacteria on CF, although SWCNTs did not attach to CF. In contrast, SWCNTs functionalized by small-sized surfactants led to a decrease in both currents and the amount of bacteria in the solution, presumably due to the detachment of surfactants from SWCNTs and their detrimental interaction with cells. We expect our results will help researchers in designing materials for smart bioelectrical interfaces for low-scale microbial energy harvesting, sensing, and energy conversion applications.

The ability of small lipophilic molecules to penetrate the blood-brain barrier through transmembrane diffusion has enabled researchers to explore new diagnostics and therapies for brain disorders. Until now, therapies targeting the brain have mainly relied on biochemical mechanisms, while electrical treatments such as deep brain stimulation often require invasive procedures. An alternative to implanting deep brain stimulation probes could involve administering small molecule precursors intravenously, capable of crossing the blood-brain barrier, and initiating the formation of conductive polymer networks in the brain through in vivo polymerization. This study examines the aggregation behavior of five water-soluble conducting polymer precursors sharing the same conjugate core but differing in side chains, using spectroscopy and various computational chemistry tools. Our findings highlight the significant impact of side chain composition on both aggregation and spectroscopic response.

Organic electrochemical transistors (OECTs) have emerged as promising candidates for various fields, including bioelectronics, neuromorphic computing, biosensors, and wearable electronics. OECTs operate in aqueous solutions, exhibit high amplification properties, and offer ion-to-electron signal transduction. The OECT channel consists of a conducting polymer, with PEDOT:PSS receiving the most attention to date. While PEDOT:PSS is highly conductive, and benefits from optimized protocols using secondary dopants and detergents, new p-type and n-type polymers are emerging with desirable material properties. Among these, low-oxidation potential oligomers are highly enabling for bioelectronics applications, however the polymers resulting from their polymerization lag far behind in conductivity compared with the established PEDOT:PSS. In this work we show that by careful design of the OECT geometrical characteristics, we can overcome this limitation and achieve devices that are on-par with transistors employing PEDOT:PSS. We demonstrate that the vertical architecture allows for facile electropolymerization of a family of trimers that are polymerized in very low oxidation potentials, without the need for harsh chemicals or secondary dopants. Vertical and planar OECTs are compared using various characterization methods. We show that vOECTs are superior platforms in general and propose that the vertical architecture can be expanded for the realization of OECTs for various applications.

Despite a range of available pain therapies, most patients report so-called “breakthrough pain.” Coupled with global issues like opioid abuse, there is a clear need for advanced therapies and technologies for safe and effective pain management. Here the authors demonstrate a candidate for such an advanced therapy: precise and fluid-flow-free electrophoretic delivery via organic electronic ion pumps (OEIPs) of the commonly used anesthetic drug bupivacaine. Bupivacaine is delivered to dorsal root ganglion (DRG) neurons in vitro. DRG neurons are a good proxy for pain studies as they are responsible for relaying ascending sensory signals from nociceptors (pain receptors) in the peripheral nervous system to the central nervous system. Capillary based OEIPs are used due to their probe-like and free-standing form factor, ideal for interfacing with cells. By delivering bupivacaine with the OEIP and recording dose versus response (Ca²⁺ imaging), it is observed that only cells close to the OEIP outlet (≤75 µm) are affected (“anaesthetized”) and at concentrations up to 10s of thousands of times lower than with bulk/bolus delivery. These results demonstrate the first effective OEIP deliveryof a clinically approved and widely used analgesic pharmaceutical, and thus are a major translational milestone for this technology.

The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious micro processing techniques. Here, we report the development of an inkjet printable formulation of polyelectrolyte, based on a custom anionically functionalized hyperbranched polyglycerol (i-AHPG). This polyelectrolyte ink greatly simplifies the fabrication process, and is used in the production of free standing, OEIPs on flexible polyimide substrates. Both i-AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by transport and delivery of the pharmaceutical compound bupivacaine to dorsal root ganglion cells with high spatial precision and effective nerve-blocking, highlighting the applicability of these technologies for biomedical scenarios.

Plant vasculature transports molecules that play a crucial role in plant signaling including systemic responses and acclimation to diverse environmental conditions. Targeted controlled delivery of molecules to the vascular tissue can be a biomimetic way to induce long distance responses, providing a new tool for the fundamental studies and engineering of stress-tolerant plants. Here, a flexible organic electronic ion pump, an electrophoretic delivery device, for controlled delivery of phytohormones directly in plant vascular tissue is developed. The c-OEIP is based on polyimide-coated glass capillaries that significantly enhance the mechanical robustness of these microscale devices while being minimally disruptive for the plant. The polyelectrolyte channel is based on low-cost and commercially available precursors that can be photocured with blue light, establishing much cheaper and safer system than the state-of-the-art. To trigger OEIP-induced plant response, the phytohormone abscisic acid (ABA) in the petiole of intact Arabidopsis plants is delivered. ABA is one of the main phytohormones involved in plant stress responses and induces stomata closure under drought conditions to reduce water loss and prevent wilting. The OEIP-mediated ABA delivery triggered fast and long-lasting stomata closure far away from the delivery point demonstrating systemic vascular transport of the delivered ABA, verified delivering deuterium-labeled ABA.

Organic electrochemical transistors (OECTs) are being researched for various applications, ranging from sensors to logic gates and neuromorphic hardware. To meet the requirements of these diverse applications, the device fabrication process must be compatible with flexible and scalable digital techniques. Here, we report a direct-write additive process to fabricate fully 3D-printed OECTs, using 3D printable conducting, semiconducting, insulating, and electrolyte inks. These 3D-printed OECTs, which operate in the depletion mode, can be fabricated on flexible substrates, resulting in high mechanical and environmental stability. The 3D-printed OECTs have good dopamine biosensing capabilities (limit of detection down to 6 mu M without metal gate electrodes) and show long-term (similar to 1 h) synapse response, indicating their potential for various applications such as sensors and neuromorphic hardware. This manufacturing strategy is suitable for applications that require rapid design changes and digitally enabled direct-write techniques.

Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems. The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging. To address this incompatibility, we developed a method to dynamically create soft substrate-free conducting materials within the biological environment. We demonstrate in vivo electrode formation in zebrafish and leech models, using endogenous metabolites to trigger enzymatic polymerization of organic precursors within an injectable gel, thereby forming conducting polymer gels with long-range conductivity. This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo-fabricated electronics within the nervous system.

We demonstrate an organic electrochemical transistor (OECT) biosensor for the detection of interleukin 6 (IL6), an important biomarker associated with various pathological processes, including chronic inflammation, inflammaging, cancer, and severe COVID-19 infection. The biosensor is functionalized with oligonucleotide aptamers engineered to bind specifically IL6. We developed an easy functionalization strategy based on gold nanoparticles deposited onto a poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) gate electrode for the subsequent electrodeposition of thiolated aptamers. During this functionalization step, the reduction of sulfide bonds allows for simultaneous deposition of a blocking agent. A detection range from picomolar to nanomolar concentrations for IL6 was achieved, and the selectivity of the device was assessed against Tumor Necrosis Factor (TNF), another cytokine involved in the inflammatory processes.

Plants are able to sense and respond to a myriad of external stimuli, using different signal transduction pathways, including electrical signaling. The ability to monitor plant responses is essential not only for fundamental plant science, but also to gain knowledge on how to interface plants with technology. Still, the field of plant electrophysiology remains rather unexplored when compared to its animal counterpart. Indeed, most studies continue to rely on invasive techniques or on bulky inorganic electrodes that oftentimes are not ideal for stable integration with plant tissues. On the other hand, few studies have proposed novel approaches to monitor plant signals, based on non-invasive conformable electrodes or even organic transistors. Organic electrochemical transistors (OECTs) are particularly promising for electrophysiology as they are inherently amplification devices, they operate at low voltages, can be miniaturized, and be fabricated in flexible and conformable substrates. Thus, in this study, we characterize OECTs as viable tools to measure plant electrical signals, comparing them to the performance of the current standard, Ag/AgCl electrodes. For that, we focused on two widely studied plant signals: the Venus flytrap (VFT) action potentials elicited by mechanical stimulation of its sensitive trigger hairs, and the wound response of Arabidopsis thaliana. We found that OECTs are able to record these signals without distortion and with the same resolution as Ag/AgCl electrodes and that they offer a major advantage in terms of signal noise, which allow them to be used in field conditions. This work establishes these organic bioelectronic devices as non-invasive tools to monitor plant signaling that can provide insight into plant processes in their natural environment.

There is increasing demand for direct in situ metabolite monitoring from cell cultures and in vivo using implantable devices. Electrochemical biosensors are commonly preferred due to their low-cost, high sensitivity, and low complexity. Metabolite detection, however, in cultured cells or sensitive tissue is rarely shown. Commonly, glucose sensing occurs indirectly by measuring the concentration of hydrogen peroxide, which is a by-product of the conversion of glucose by glucose oxidase. However, continuous production of hydrogen peroxide in cell media with high glucose is toxic to adjacent cells or tissue. This challenge is overcome through a novel, stacked enzyme configuration. A primary enzyme is used to provide analyte sensitivity, along with a secondary enzyme which converts H2O2 back to O-2. The secondary enzyme is functionalized as the outermost layer of the device. Thus, production of H2O2 remains local to the sensor and its concentration in the extracellular environment does not increase. This "biostack" is integrated with organic electrochemical transistors to demonstrate sensors that monitor glucose concentration in cell cultures in situ. The "biostack" renders the sensors nontoxic for cells and provides highly sensitive and stable detection of metabolites.

Organic electronic ion pumps (OEIPs) have been investigated as a promising solution for precise local delivery of biological signaling compounds. OEIP miniaturization provides several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted devices. One miniaturization route is to develop OEIPs based on polyelectrolyte-filled capillary fibers. These devices can be easily brought into proximity of targeted cells and tissues and could be considered as a starting point for other "iontronic" implants. To date, OEIPs and other such iontronics exhibit a limited electrode capacity as they generally rely on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) electrodes. While this material is well studied and viable in mixed ion-electron systems, its bulk capacitance is limited by eventual redox reactions. Graphene is an excellent alternative for high-performance electrodes and low-cost solution-processed graphene derivatives are particularly promising, exhibiting high charge mobility and ideal structural properties (lightness, flexibility). Here, the application of solution-processed reduced graphene oxide (RGO) as high-performance driving electrodes for OEIPS is presented. RGO electrodes are characterized and compared with standard PEDOT:PSS (and Ag/AgCl) electrodes. The RGO exhibits greater charge storage capacity and thus increased operational lifetime. The graphene-enabled OEIPs exhibit improved neurotransmitter transport, without imposing limitations to the applied current level.

The nervous system poses a grand challenge for integration with modern electronics and the subsequent advances in neurobiology, neuroprosthetics, and therapy which would become possible upon such integration. Due to its extreme complexity, multifaceted signaling pathways, and similar to 1 kHz operating frequency, modern complementary metal oxide semiconductor (CMOS) based electronics appear to be the only technology platform at hand for such integration. However, conventional CMOS-based electronics rely exclusively on electronic signaling and therefore require an additional technology platform to translate electronic signals into the language of neurobiology. Organic electronics are just such a technology platform, capable of converting electronic addressing into a variety of signals matching the endogenous signaling of the nervous system while simultaneously possessing favorable material similarities with nervous tissue. In this review, we introduce a variety of organic material platforms and signaling modalities specifically designed for this role as "translator" , focusing especially on recent implementation in in vivo neuromodulation. We hope that this review serves both as an informational resource and as an encouragement and challenge to the field.

State-of-the-art technology based on organic electronics can be used as a flow-free delivery method for organic substances with high spatial resolution. Such highly targeted drug micro applications can be used in plant research for the regulation of physiological processes on tissue and cellular levels. Here, for the first time, an organic electronic ion pump (OEIP) is reported that can transport an isoprenoid-type cytokinin, N-6-isopentenyladenine (iP), to intact plants. Cytokinins (CKs) are plant hormones involved in many essential physiological processes, including primary root (PR) and lateral root (LR) development. Using the Arabidopsis thaliana root as a model system, efficient iP delivery is demonstrated with a biological output - cytokinin-related PR and LR growth inhibition. The spatial resolution of iP delivery, defined for the first time for an organic compound, is shown to be less than 1 mm, exclusively affecting the OEIP-targeted LR. Results from the application of the high-resolution OIEP treatment method confirm previously published findings showing that the influence of CKs may vary at different stages of LR development. Thus, OEIP-based technologies offer a novel, electronically controlled method for phytohormone delivery that could contribute to unraveling cytokinin functions during different developmental processes with high specificity.

The dimensions of the material serving as the channel in organic electrochemical transistors (OECTs) are important for the overall switching performance. Here, a laser ablation step is included in the OECT manufacturing process, in an attempt to shorten the channel length of the OECT. The source and drain electrodes are formed by laser ablation of a previously screen printed carbon-based rectangle, which in this study resulted in an average channel length equal to 25 mu m. All other processing steps rely on screen printing, allowing for large-area manufacturing of OECTs and OECT-based circuits on flexible substrates. This approach results in a manufacturing yield of 89%; 178 out of a total of 200 OECTs exhibited an ON/OFF ratio exceeding 1000 with a statistical mean value of 28 000 and reproducible switching performance. OECT-based circuits, here demonstrated by a logic inverter, provide a reasonably high voltage gain of 12. The results thus demonstrate another reliable OECT manufacturing process, based on the combination of laser ablation and screen printing.

Organic electrochemical transistors formed by in operando electropolymerization of the semiconducting channel are increasingly becoming recognized as a simple and effective implementation of synapses in neuromorphic hardware. However, very few studies have reported the requirements that must be met to ensure that the polymer spreads along the substrate to form a functional conducting channel. The nature of the interface between the substrate and various monomer precursors of conducting polymers through molecular dynamics simulations is investigated, showing that monomer adsorption to the substrate produces an increase in the effective monomer concentration at the surface. By evaluating combinatorial couples of monomers baring various sidechains with differently functionalized substrates, it is shown that the interactions between the substrate and the monomer precursor control the lateral growth of a polymer film along an inert substrate. This effect has implications for fabricating synaptic systems on inexpensive, flexible substrates.

Biomimicry at the hardware level is expected to overcome at least some of the challenges, including high power consumption, large footprint, two-dimensionality, and limited functionality, which arise as the field of artificial intelligence matures. One of the main attributes that allow biological systems to thrive is the successful interpretation of and response to environmental signals. Taking inspiration from these systems, the first demonstration of using multiple environmental inputs to trigger the formation and control the growth of an evolvable synaptic transistor is reported here. The resulting transistor exhibits long-term changes in the channel conductance at a fixed gate voltage. Biomimetic logic circuits are investigated based on this evolvable transistor that implement temperature and pressure inputs to achieve higher order processes like self-regulation of synaptic strength and coincidence detection.

Body area networks (BANs), cloud computing, and machine learning are platforms that can potentially enable advanced healthcare outside the hospital. By applying distributed sensors and drug delivery devices on/in our body and connecting to such communication and decision-making technology, a system for remote diagnostics and therapy is achieved with additional autoregulation capabilities. Challenges with such autarchic on-body healthcare schemes relate to integrity and safety, and interfacing and transduction of electronic signals into biochemical signals, and vice versa. Here, we report a BAN, comprising flexible on-body organic bioelectronic sensors and actuators utilizing two parallel pathways for communication and decision-making. Data, recorded from strain sensors detecting body motion, are both securely transferred to the cloud for machine learning and improved decision-making, and sent through the body using a secure body-coupled communication protocol to auto-actuate delivery of neurotransmitters, all within seconds. We conclude that both highly stable and accurate sensing-from multiple sensors-are needed to enable robust decision making and limit the frequency of retraining. The holistic platform resembles the self-regulatory properties of the nervous system, i.e., the ability to sense, communicate, decide, and react accordingly, thus operating as a digital nervous system.

The organic electronic ion pump (OEIP) delivers ions and charged drugs from a source electrolyte, through a charge-selective membrane, to a target electrolyte upon an electric bias. OEIPs have successfully delivered γ-aminobutyric acid (GABA), a neurotransmitter that reduces neuronal excitations, in vitro, and in brain tissue to terminate induced epileptic seizures. However, during pumping, protons (H+), which exhibit higher ionic mobility than GABA, are also delivered and may potentially cause side effects due to large local changes in pH. To reduce the proton transfer, we introduced proton traps along the selective channel membrane. The traps are based on palladium (Pd) electrodes, which selectively absorb protons into their structure. The proton-trapping Pd-OEIP improves the overall performance of the current state-of-the-art OEIP, namely, its temporal resolution, efficiency, selectivity, and dosage precision.

Implantable bioelectronic devices pave the way for novel biomedical applications operating at high spatiotemporal resolution, which is crucial for neural recording and stimulation, drug delivery, and brain-machine interfaces. Before successful long-term implantation and clinical applications, these devices face a number of challenges, such as mechanical and operational stability, biocompatibility, miniaturization, and powering. To address two of these crucial challenges-miniaturization and powering-the development and characterization of an electrophoretic drug delivery device, manufactured inside fused quartz fibers (outer diameter of 125 mu m), which is self-powered by a flexible piezoelectric energy harvester, are reported. The resulting device-the first integration of piezoelectric charging with "iontronic" delivery-exhibits a high delivery efficiency (number of neurotransmitters delivered per charges applied) and a direct correlation between the piezoelectric charging and the amount delivered (number of dynamic bends versus pmols delivered).

Fibrosis and scar formation is a medical condition observed under various circumstances, ranging from skin wound healing to cardiac deterioration after myocardial infarction. Among other complex interdependent phases during wound healing, fibrosis is associated with an increased fibroblast to myofibroblast transition. A common hypothesis is that decreasing the pH of non-healing, alkaline wounds to a pH range of 6.0 to 6.5 increases healing rates. A new material-based strategy to change the pH by use of electronic ion pumps is here proposed. In contrast to passive acidic wound dressings limited by non-controlled delivery kinetics, the unique electronic ion pump design and operation enables a continuous regulation of pH by H+ delivery over prolonged durations. In an in vitro model, fibroblast to myofibroblast differentiation is attenuated by lowering the physiological pH to an acidic regime of 6.62 +/- 0.06. Compared to differentiated myofibroblasts in media at pH 7.4, gene and protein expression of fibrosis relevant markers alpha-smooth muscle actin and collagen 1 is significantly reduced. In conclusion, myofibroblast differentiation can be steered by controlling the pH of the cellular microenvironment by use of the electronic ion pump technology as new bioelectronic drug delivery devices. This technology opens up new therapeutic avenues to induce scar-free wound healing. (C) 2021 The Authors. Published by Elsevier Ltd.

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Highly controlled drug delivery devices play an increasingly important role in the development of new neuroengineering tools. Stringent - and sometimes contradicting - demands are placed on such devices, ranging from robustness in freestanding devices, to overall device miniaturization, while maintaining precise spatiotemporal control of delivery with high chemical specificity and high on/off ratio. Here, design principles of a hybrid microfluidic iontronic probe that uses flow for long-range pressure-driven transport in combination with an iontronic tip that provides electronically fine-tuned pressure-free delivery are explored. Employing a computational model, the effects of decoupling the drug reservoir by exchanging a large passive reservoir with a smaller microfluidic system are reported. The transition at the microfluidic-iontronic interface is found to require an expanded ion exchange membrane inlet in combination with a constant fluidic flow, to allow a broad range of device operation, including low source concentrations and high delivery currents. Complementary to these findings, the free-standing hybrid probe monitored in real time by an external sensor is demonstrated. From these computational and experimental results, key design principles for iontronic devices are outlined that seek to use the efficient transport enabled by microfluidics, and further, key observations of hybrid microfluidic iontronic probes are explained.

Bioelectronic devices that convert biochemical signals to electronic readout enable biosensing with high spatiotemporal resolution. These technologies have been primarily applied in biomedicine while in plants sensing is mainly based on invasive methods that require tissue sampling, hindering in-vivo detection and having poor spatiotemporal resolution. Here, we developed enzymatic biosensors based on organic electrochemical transistors (OECTs) for in-vivo and real-time monitoring of sugar fluctuations in the vascular tissue of trees. The glucose and sucrose OECT-biosensors were implanted into the vascular tissue of trees and were operated through a low-cost portable unit for 48hr. Our work consists a proof-of-concept study where implantable OECT-biosensors not only allow real-time monitoring of metabolites in plants but also reveal new insights into diurnal sugar homeostasis. We anticipate that this work will contribute to establishing bioelectronic technologies as powerful minimally invasive tools in plant science, agriculture and forestry.

Introduction: Bone fractures remain a common injury. Nonunion fractures are often a serious complication where delays in tissue regeneration occur. The use of pulsed electromagnetic fields (PEMFs) for treatment has been studied for years, having reportedly been able to enhance bone regeneration. However, as various PEMF parameters can affect cellular properties differently, it is necessary to adjust each PEMF parameter to achieve the optimal regeneration. Methods: Primary rabbit mesenchymal stem cells (rMSCs) were cultured in vitro in two types of media, namely nondifferentiation and osteogenic differentiation media. The effect of various intensities of PEMF was assessed by evaluating properties such as cellular metabolism, proliferation, and osteogenic differentiation at different time points. Results: The findings suggest that PEMFs had no adverse effect on cellular morphology and mineralization. In contrast, increased metabolic activity was observed at higher PEMF intensity, whereas moderate PEMF intensities had the strongest effect on cell proliferation in both types of culture media. A comparison study was also done between the primary rMSCs against the MC3T3-E1 cells from a previously published article. It was shown that PEMFs improved cell metabolism of MSCs, while maintaining the metabolic activity of MC3T3. Conclusions: PEMFs generally improved cell proliferation for both cell types, whereas leaving cell mineralization unaffected. Taken together, it can be understood that the optimal application of PEMF stimulus, along with the right cell types, is indeed crucial in achieving effective bone regeneration in vitro.

Organic electrochemical transistors (OECTs) have gained significant interest in recent years due to their ability to transduce and amplify biochemical signals into easily recorded electrical signals. The magnitude of the amplification offered by an OECT is proportional to its transconductance, gm, making gm an important figure of merit. Much attention has, therefore, been paid to the materials and device geometries, which can maximize an OECT's gm. However, less attention has been paid to the role of the applied potentials and various operational regimes. In this paper, we expand on the seminal Bernards and Malliaras model of the OECT function to include negative gate potentials, allowing prediction of gm and general biosensor performance over a broader application range. The expanded model results in five operational regimes, only two of which were covered by the original model. We find an optimal combination of drain and (negative) gate potentials yielding maximal gm. We also find that reducing the pinch-off potential well below the water-splitting limit can yield larger operational windows at the highest gm. Our expanded model presents a general set of guidelines for OECT operation, yielding the highest possible gm, and, therefore, optimal amplification and associated (bio)sensor performance. 

Supported lipid bilayers (SLBs) serve important roles as minimalistic models of cellular membranes in multiple diagnostic and pharmaceutical applications as well as in the strive to gain fundamental insights about their complex biological function. To further expand the utility of SLBs, there is a need to go beyond simple lipid compositions to thereby better mimic the complexity of native cell membranes, while simultaneously retaining their compatibility with a versatile range of analytical platforms. To meet this demand, we have in this work explored SLB formation on PEDOT:PSS/silica nanoparticle composite films and mesoporous silica films, both capable of transporting ions to an underlying conducting PEDOT:PSS film. The SLB formation process was evaluated by using the quartz crystal microbalance with dissipation (QCM-D) monitoring, total internal reflection fluorescence (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) for membranes made of pure synthetic lipids with or without the reconstituted membrane protein β-secretase 1 (BACE1) as well as cell-derived native lipid vesicles containing overexpressed BACE1. The mesoporous silica thin film was superior to the PEDOT:PSS/silica nanoparticle composite, providing successful formation of bilayers with high lateral mobility and low defect density even for the most complex native cell membranes.

Polymer-based ion exchange membranes (IEMs) are utilized for many applications such as in water desalination, energy storage, fuel cells and in electrophoretic drug delivery devices, exemplified by the organic electronic ion pump (OEIP). The bulk of current research is primarily focused on finding highly conductive and stable IEM materials. Even though great progress has been made, a lack of fundamental understanding of how specific polymer properties affect ionic transport capabilities still remains. This leads to uncertainty in how to proceed with synthetic approaches for designing better IEM materials. In this study, an investigation of the structure-property relationship between polymer size and ionic conductivity was performed by comparing a series of membranes, based on ionically charged hyperbranched polyglycerol of different polymer sizes. Observing an increase in ionic conductivity associated with increasing polymer size and greater electrolyte exclusion, indi-cating an ionic transportation phenomenon not exclusively based on membrane electrolyte uptake. These findings further our understanding of ion transport phenomena in semi-permeable membranes and indicate a strong starting point for future design and synthesis of IEM polymers to achieve broader capabilities for a variety of ion transport-based applications.

An overview of cytokine biosensing is provided, with a focus on the opportunities provided by organic electronic platforms for monitoring these inflammation biomarkers which manifest at ultralow concentration levels in physiopathological conditions. Specifically, two of the fields state-of-the-art technologies-organic electrochemical transistors (OECTs) and electrolyte gated organic field effect transistors (EGOFETs)-and their use in sensing cytokines and other proteins associated with inflammation are a particular focus. The overview will include an introduction to current clinical and "gold standard" quantification techniques and their limitations in terms of cost, time, and required infrastructure. A critical review of recent progress with OECT- and EGOFET-based protein biosensors is presented, alongside a discussion onthe future of these technologies in the years and decades ahead. This is especially timely as the world grapples with limited healthcare diagnostics during the Coronavirus disease (COVID-19)pandemic where one of the worst-case scenarios for patients is the "cytokine storm." Clearly, low-cost point-of-care technologies provided by OECTs and EGOFETs can ease the global burden on healthcare systems and support professionals by providing unprecedented wealth of data that can help to monitor disease progression in real time.

Implantable electronically controlled drug delivery devices can provide precision therapeutic treatments by highly spatiotemporally controlled delivery. Iontronic delivery devices rely on the movement of ions rather than liquid, and can therefore achieve electronically controlled precision delivery in a compact setting without disturbing the microenvironment within the tissue with fluid flow. For maximum precision, the delivery device needs to be closely integrated into the tissue, which is challenging due to the mechanical mismatch between the soft tissue and the harder devices. Here we address this challenge by developing a soft and stretchable iontronic delivery device. By formulating an ink based on an in-house synthesized hyperbranched polyelectrolyte, water dispersed polyurethane, and a thickening agent, a viscous ink is developed for stencil patterning of soft ion exchange membranes (IEMs). We use this ink for developing soft and stretchable delivery devices, which are characterized both in the relaxed and stretched state. We find that their functionality is preserved up to 100% strain, with small variations in resistance due to the strain. Finally, we develop a skin patch to demonstrate the outstanding conformability of the developed device. The presented technology is attractive for future soft implantable delivery devices, and the stretchable IEMs may also find applications within wearable energy devices.

Bone exhibits piezoelectric properties. Thus, electrical stimulations such as pulsed electromagnetic fields (PEMFs) and stimuli-responsive piezoelectric properties of scaffolds have been investigated separately to evaluate their efficacy in supporting osteogenesis. However, current understanding of cells responding under the combined influence of PEMF and piezoelectric properties in scaffolds is still lacking. Therefore, in this study, we fabricated piezoelectric scaffolds by functionalization of polycaprolactone-tricalcium phosphate (PCL-TCP) films with a polyvinylidene fluoride (PVDF) coating that is self-polarized by a modified breath-figure technique. The osteoinductive properties of these PVDF-coated PCL-TCP films on MC3T3-E1 cells were studied under the stimulation of PEMF. Piezoelectric and ferroelectric characterization demonstrated that scaffolds with piezoelectric coefficient d(33) = -1.2 pC/N were obtained at a powder dissolution temperature of 100 degrees C and coating relative humidity (RH) of 56%. DNA quantification showed that cell proliferation was significantly enhanced by PEMF as low as 0.6 mT and 50 Hz. Hydroxyapatite staining showed that cell mineralization was significantly enhanced by incorporation of PVDF coating. Gene expression study showed that the combination of PEMF and PVDF coating promoted late osteogenic gene expression marker most significantly. Collectively, our results suggest that the synergistic effects of PEMF and piezoelectric scaffolds on osteogenesis provide a promising alternative strategy for electrically augmented osteoinduction. The piezoelectric response of PVDF by PEMF, which could provide mechanical strain, is particularly interesting as it could deliver local mechanical stimulation to osteogenic cells using PEMF.

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 10(4)-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.

The organic electrochemical transistor (OECT) has attracted interest for use in biosensor technology due to its ability to transduce ionic to electronic signals and operate in aqueous environments. While OECTs have been broadly applied for biosensing and impedance characterization of biological systems, there is still no consensus on the ideal geometries, relative capacitances, and operational conditions for specific sensing scenarios. Here it is shown that for impedance sensing with a capacitive layer on the gate, gate-limited OECTs produce the largest sensor response. An equivalent circuit model is used to study frequency response with non-permeable and ion-permeable membranes added to the gate and found that the transistor configuration, with respect to gate and channel capacitances, able to produce the largest sensor signal is determined by the capacitance to be sensed as well as the membrane permeability. The findings are applied to design a gold gate OECT capable of detecting formation of a lipid bilayer on the gate. The results indicate that high transconductance OECTs typically considered attractive do not deliver the largest sensor signals when used for impedance sensing. Results are presented in settings similar to those used in practical experiments, thereby providing guidance on how to best design OECTs for impedance biosensing.

Low-cost, minimally invasive sensors able to provide real-time monitoring of wound infection can enable the optimization of healthcare resources in chronic wounds management. Here, a novel printed organic electrochemical transistors (OECT) biosensor for monitoring uric acid (UA), a bacterial infection biomarker in wounds, is demonstrated in artificial wound exudate. The sensor exploits the enzymatic conversion of UA to 5-hydroxyisourate, catalyzed by Uricase entrapped in a dual-ionic-layer hydrogel membrane casted onto the gate. The sensor response is based on the catalytic oxidation of the hydrogen peroxide, generated as part of the Uricase regeneration process, at the Pt modified gate. The proposed dual membrane avoids the occurrence of nonspecific faradic reactions as, for example, the direct oxidation of UA or other electroactive molecules that would introduce a potentially false negative response. The biosensor is robust and its response is reproducible both in phosphate buffer saline and in complex solutions mimicking the wound exudate. The sensor has a high sensitivity in the range encompassing the pathological levels of UA in wounds (<200 mu m) exhibiting a limit of detection of 4.5 mu m in artificial wound exudate. All these characteristics make this OECT-based biosensor attractive for wound monitoring interfaced to the patient.

Current neural interfaces rely on electrical stimulation pulses to affect neural tissue. The development of a chemical delivery technology, which can stimulate neural tissue with the bodys own set of signaling molecules, would provide a new level of sophistication in neural interfaces. Such technology should ideally provide highly local chemical delivery points that operate at synaptic speed, something that is yet to be accomplished. Here, the development of a miniaturized ionic polarization diode that exhibits many of the desirable properties for a chemical neural interface technology is reported. The ionic diode shows proper diode rectification and the current switches from off to on in 50 mu s at physiologically relevant electrolyte concentrations. A device model is developed to explain the characteristics of the ionic diode in more detail. In combination with experimental data, the model predicts that the ionic polarization diode has a delivery delay of 5 ms to reach physiologically relevant neurotransmitter concentrations at subcellular spatial resolution. The model further predicts that delays of amp;lt;1 ms can be reached by further miniaturization of the diode geometry. Altogether, the results show that ionic polarization diodes are a promising building block for the next generation of chemical neural interfaces.

Extracellular electron transfer (EET) denotes the process of microbial respiration with electron transfer to extracellular acceptors and has been exploited in a range of microbial electrochemical systems (MESs). To further understand EET and to optimize the performance of MESs, a better understanding of the dynamics at the microscale is needed. However, the real-time monitoring of EET at high spatiotemporal resolution would require sophisticated signal amplification. To amplify local EET signals, a miniaturized bioelectronic device, the so-called organic microbial electrochemical transistor (OMECT), is developed, which includes Shewanella oneidensis MR-1 integrated onto organic electrochemical transistors comprising poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) combined with poly(vinyl alcohol) (PVA). Bacteria are attached to the gate of the transistor by a chronoamperometric method and the successful attachment is confirmed by fluorescence microscopy. Monitoring EET with the OMECT configuration is achieved due to the inherent amplification of the transistor, revealing fast time-responses to lactate. The limits of detection when using microfabricated gates as charge collectors are also investigated. The work is a first step toward understanding and monitoring EET in highly confined spaces via microfabricated organic electronic devices, and it can be of importance to study exoelectrogens in microenvironments, such as those of the human microbiome.

Biosensors based on organic electrochemical transistors (OECT) are attractive devices for real-time monitoring of biological processes. The direct coupling between the channel of the OECT and the electrolyte enables intimate interfacing with biological environments at the same time bringing signal amplification and fast sensor response times. So far, these devices are mainly applied to mammalian systems; cells or body fluids for the development of diagnostics and various health status monitoring technology. Yet, no direct detection of biomolecules from cells or organelles is reported. Here, an OECT glucose sensor applied to chloroplasts, which are the plant organelles responsible for the light-to-chemical energy conversion of the photosynthesis, is reported. Real-time monitoring of glucose export from chloroplasts in two distinct metabolic phases is demonstrated and the transfer dynamics with a time resolution of 1 min is quantified, thus reaching monitoring dynamics being an order of magnitude better than conventional methods.

Energy harvesting from photosynthetic membranes, proteins, or bacteria through bio-photovoltaic or bio-electrochemical approaches has been proposed as a new route to clean energy. A major shortcoming of these and solar cell technologies is the underutilization of solar irradiation wavelengths in the IR region, especially those in the far IR region. Here, a biohybrid energy-harvesting device is demonstrated that exploits IR radiation, via convection and thermoelectric effects, to improve the resulting energy conversion performance. A composite of nanocellulose and the conducting polymer system poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is used as the anode in biohybrid cells that includes thylakoid membranes (TMs) and redox mediators (RMs) in solution. By irradiating the conducting polymer electrode by an IR light-emitting diode, a sixfold enhancement in the harvested bio-photovoltaic power is achieved, without compromising stability of operation. Investigation of the output currents reveals that IR irradiation generates convective heat transfer in the electrolyte bulk, which enhances the redox reactions of RMs at the anode by suppressing diffusion limitations. In addition, a fast-transient thermoelectric component, originating from the PEDOT:PSS-nanocellulose-electrolyte interphase, further increases the bio-photocurrent. These results pave the way for the development of energy-harvesting biohybrids that make use of heat, via IR absorption, to enhance energy conversion efficiency.

Transcranial electrical stimulation is a noninvasive neurostimulation technique with a wide range of therapeutic applications. However, current electrode materials are typically not optimized for this abiotic/biotic interface which requires high charge capacity, operational stability, and conformability. Here, a plant-based composite electrode material based on the combination of aloe vera (AV) hydrogel and a conducting polymer (CP; poly(3,4-ethylenedioxythiophene):polystyrene sulfonate, PEDOT:PSS) is reported. This material system is fabricated into films and provides biocompatibility, conformability, and stability, while offering desirable electrical properties of the PEDOT:PSS. AVCP films are also molded onto the rough surface of the skull leading to a mechanically stable and robust interface. The in vivo efficacy of the AVCP films is verified to function as stimulating and recording electrodes by placing them on the skull of a rat and concomitantly inducing focal seizures and acquiring the evoked neural activity. AVCP films pave the way for high-quality biological interfaces that are broadly applicable and can facilitate advances in closed-loop responsive stimulation devices.

During the last decades, tremendous efforts have been carried out to develop flexible electronics for a vast array of applications. Among all different applications investigated in this area, flexible displays have gained significant attention, being a vital part of large-area devices, portable systems and electronic labels etc electrophoretic (EP) ink displays have outstanding properties such as a superior optical switch contrast and low power consumption, besides being compatible with flexible electronics. However, the EP ink technology requires an active matrix-addressing scheme to enable exclusive addressing of individual pixels. EP ink pixels cannot be incorporated in low cost and easily manufactured passive matrix circuits due to the lack of threshold voltage and nonlinearity, necessities to provide addressability. Here, we suggest a simple method to introduce nonlinearity and threshold voltage in EP ink display cells in order to make them passively addressable. Our method exploits the nonlinearity of an organic ferroelectric capacitor that introduces passive addressability in display cells. The organic ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) is here chosen because of its simple manufacturing protocol and good polarizability. We demonstrate that a nonlinear EP cell with bistable states can be produced by depositing a P(VDF-TrFE) film on the bottom electrode of the display cell. The P(VDF-TrFE) capacitor and the EP ink cell are separately characterized in order to match the surface charge at their respective interfaces and to achieve and optimize bistable operation of display pixels.

An evolvable organic electrochemical transistor (OECT), operating in the hybrid accumulation-depletion mode is reported, which exhibits short-term and long-term memory functionalities. The transistor channel, formed by an electropolymerized conducting polymer, can be formed, modulated, and obliterated in situ and under operation. Enduring changes in channel conductance, analogous to long-term potentiation and depression, are attained by electropolymerization and electrochemical overoxidation of the channel material, respectively. Transient changes in channel conductance, analogous to short-term potentiation and depression, are accomplished by inducing nonequilibrium doping states within the transistor channel. By manipulating the input signal, the strength of the transistor response to a given stimulus can be modulated within a range that spans several orders of magnitude, producing behavior that is directly comparable to short- and long-term neuroplasticity. The evolvable transistor is further incorporated into a simple circuit that mimics classical conditioning. It is forecasted that OECTs that can be physically and electronically modulated under operation will bring about a new paradigm of machine learning based on evolvable organic electronics.

Organic electronics, in combination with custom polyelectrolytes, enables solid- and hydrogel-state circuit components using ionic charges in place of the electrons of traditional electronics. This growing field of iontronics leverages anion- and cation-exchange membranes as analogs to n-type and p-type semiconductors, and conjugated polymer electrodes as ion-to-electron converters. To date, the iontronics toolbox includes ionic resistors, ionic diodes, ionic transistors, and analog and digital circuits comprised thereof. Here, an ionic capacitor based on mixed electron-ion conductors is demonstrated. The ionic capacitor resembles the structure of a conventional electrochemical capacitor that is inverted, with an electronically conducting core and two electrolyte ionic conductors. The device is first verified as a capacitor, and then demonstrated as a smoothing element in an iontronic diode bridge circuit driving an organic electronic ion pump (ionic resistor). The ionic capacitor complements the existing iontronics toolbox, enabling more complex and functional ionic circuits, and will thus have implications in a variety of mixed electron-ion conduction technologies.

Organic electronic ion pumps (OEIPs) are versatile tools for electrophoretic delivery of substances with high spatiotemporal resolution. To date, OEIPs and similar iontronic components have been fabricated using thin-film techniques and often rely on laborious, multistep photolithographic processes. OEIPs have been demonstrated in a variety of in vitro and in vivo settings for controlling biological systems, but the thin-film form factor and limited repertoire of polyelectrolyte materials and device fabrication techniques unnecessarily constrain the possibilities for miniaturization and extremely localized substance delivery, e.g., the greater range of pharmaceutical compounds, on the scale of a single cell. Here, we demonstrate an entirely new OEIP form factor based on capillary fibers that include hyperbranched polyglycerols (dPGs) as the selective electrophoretic membrane. The dPGs enable electrophoretic channels with a high concentration of fixed charges and well-controlled cross-linking and can be realized using a simple one-pot fluidic manufacturing protocol. Selective electrophoretic transport of cations and anions of various sizes is demonstrated, including large substances that are difficult to transport with other OEIP technologies. We present a method for tailoring and characterizing the electrophoretic channels fixed charge concentration in the operational state. Subsequently, we compare the experimental performance of these capillary OEIPs to a computational model and explain unexpected features in the ionic current for the transport and delivery of larger, lower-mobility ionic compounds. From this model, we are able to elucidate several operational and design principles relevant to miniaturized electrophoretic drug delivery technologies in general. Overall, the compactness of the capillary OEIP enables electrophoretic delivery devices with probelike geometries, suitable for a variety of ionic compounds, paving the way for less-invasive implantation into biological systems and for healthcare applications.

In the emerging field of organic bioelectronics, conducting polymers and ion-selective membranes are combined to form resistors, diodes, transistors, and circuits that transport and process both electronic and ionic signals. Such bioelectronics concepts have been explored in delivery devices that translate electronic addressing signals into the transport and dispensing of small charged biomolecules at high specificity and spatiotemporal resolution. Manufacturing such "iontronic" devices generally involves classical thin film processing of polyelectrolyte layers and insulators followed by application of electrolytes. This approach makes miniaturization and integration difficult, simply because the ion selective polyelectrolytes swell after completing the manufacturing. To advance such bioelectronics/iontronics and to enable applications where relatively larger molecules can be delivered, it is important to develop a versatile material system in which the charge/size selectivity can be easily tailormade at the same time enabling easy manufacturing of complex and miniaturized structures. Here, we report a one-pot synthesis approach with minimal amount of organic solvent to achieve cationic hyperbranched polyglycerol films for iontronics applications. The hyperbranched structure allows for tunable pre multi-functionalization, which combines available unsaturated groups used in crosslinking along with ionic groups for electrolytic properties, to achieve a one-step process when applied in devices for monolithic membrane gel formation with selective electrophoretic transport of molecules.

Electronic control of biological processes with bioelectronic devices holds promise for sophisticated regulation of physiology, for gaining fundamental understanding of biological systems, providing new therapeutic solutions, and digitally mediating adaptations of organisms to external factors. The organic electronic ion pump (OEIP) provides a unique means for electronically-controlled, flow-free delivery of ions, and biomolecules at cellular scale. Here, a miniaturized OEIP device based on glass capillary fibers (c-OEIP) is implanted in a biological organism. The capillary form factor at the sub-100 mu m scale of the device enables it to be implanted in soft tissue, while its hyperbranched polyelectrolyte channel and addressing protocol allows efficient delivery of a large aromatic molecule. In the first example of an implantable bioelectronic device in plants, the c-OEIP readily penetrates the leaf of an intact tobacco plant with no significant wound response (evaluated up to 24 h) and effectively delivers the hormone abscisic acid (ABA) into the leaf apoplast. OEIP-mediated delivery of ABA, the phytohormone that regulates plants tolerance to stress, induces closure of stomata, the microscopic pores in leafs epidermis that play a vital role in photosynthesis and transpiration. Efficient and localized ABA delivery reveals previously unreported kinetics of ABA-induced signal propagation.