Biological systems use a large variety of ions and molecules of different sizes for signaling. Precise electronic regulation of biological systems therefore requires an interface which translates the electronic signals into chemically specific biological signals. One technology for this purpose that has been developed during the last decade is the organic electronic ion pump (OEIP). To date, OEIPs have been fabricated by micropatterning and labor-intensive manual techniques, hindering the potential application areas of this promising technology. Here we show, for the first time, fully screen-printed OEIPs. We demonstrate a large-area printed design with manufacturing yield >90%. Screen-printed cation- and anion-exchange membranes are both demonstrated with promising ion selectivity and performance, with transport verified for both small ions (Na+, K+, Cl–) and biologically-relevant molecules (the cationic neurotransmitter acetylcholine, and the anionic anti-inflammatory salicylic acid). These advances open the ‘iontronics’ toolbox to the world of printed electronics, paving the way for a broader arena for applications.

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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.

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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 microprocessing techniques. Here, the development of an inkjet printable formulation of polyelectrolyte is reported, 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 (PI) substrates. Both i‐AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and the ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by the 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.

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 (Ca 2+ 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.

Biological systems rarely use electrons as signal regulators, most of the transport and communication in these system utilize ions. The discovery of conjugated polymers and polyelectrolytes and their unique properties of mixed ionic electronic properties opened the possibility of using these in the domain of bioelectronics, which paved the way for the field of organic bioelectronics. After the introduction of the organic electronic ion pump (OEIP) in 2007, which utilizes both the ionic properties of conjugated polymers and polyelectrolytes, the new field of "iontronics" evolved. The OEIP is an organic polymer-based delivery system based on electrophoretic transport of biologically relevant and ionically charged species, without fluid flow and with high spatial, temporal, and dosage precision. These devices have been extensively studied for the past 14 years and have found numerous demonstrations in in vivo and in vitro delivery of bio-relevant ions for therapeutic application. This has, in parallel, resulted in the development of custom materials for ion exchange membranes (IEMs) within the OEIP.

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