Imperceptible augmentation of living systems with organic bioelectronic fibres.

The functional and sensory augmentation of living structures, such as human skin and plant epidermis, with electronics can be used to create platforms for health management and environmental monitoring. Ideally, such bioelectronic interfaces should not obstruct the inherent sensations and physiological changes of their hosts. The full life cycle of the interfaces should also be designed to minimize their environmental footprint. Here we report imperceptible augmentation of living systems through in situ tethering of organic bioelectronic fibres. Using an orbital spinning technique, substrate-free and open fibre networks-which are based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate-can be tethered to biological surfaces, including fingertips, chick embryos and plants. We use customizable fibre networks to create on-skin electrodes that can record electrocardiogram and electromyography signals, skin-gated organic electrochemical transistors and augmented touch and plant interfaces. We also show that the fibres can be used to couple prefabricated microelectronics and electronic textiles, and that the fibres can be repaired, upgraded and recycled.

Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions.

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

The rise of bioelectronic medicine.

Bioelectronic Medicine (BEM), which uses implantable electronic medical devices to interface with electrically active tissues, aspires to revolutionize the way we understand and fight disease. By leveraging knowledge from microelectronics, materials science, information technology, neuroscience and medicine, BEM promises to offer novel solutions that address unmet clinical needs and change the concept of therapeutics. This perspective communicates our vision for the future of BEM and presents the necessary steps that need to be taken and the challenges that need to be faced before this new technology can flourish.

In vivo photopharmacological inhibition of hippocampal activity via multimodal probes - perspective and opening steps on experimental and computational challenges.

Neurological conditions such as epilepsy can have a significant impact on people's lives. Here, we discuss a new perspective for the study/treatment of these conditions using photopharmacology. A multimodal, intracranial implant that incorporates fluidic channels for localised drug delivery, electrodes for recording and stimulation, and a light source for photoswitching is used for in vivo administration and deactivation of a photoresponsive AMPA antagonist. We review current advancements in the relevant disciplines and show experimentally that the inhibition of seizure-like events induced in the hippocampus by electrical stimulation can be altered upon switching the drug with light. We discuss the interconnection of the drug's photopharmacological properties with the design of the device by modelling light penetration into the rat brain with Monte Carlo simulations. This work delivers a new perspective, including initial experimental and computational efforts on in vivo photopharmacology to understand and eventually treat neurological conditions.

NeuroRoots, a bio-inspired, seamless brain machine interface for long-term recording in delicate brain regions.

Scalable electronic brain implants with long-term stability and low biological perturbation are crucial technologies for high-quality brain-machine interfaces that can seamlessly access delicate and hard-to-reach regions of the brain. Here, we created "NeuroRoots," a biomimetic multi-channel implant with similar dimensions (7 µm wide and 1.5 µm thick), mechanical compliance, and spatial distribution as axons in the brain. Unlike planar shank implants, these devices consist of a number of individual electrode "roots," each tendril independent from the other. A simple microscale delivery approach based on commercially available apparatus minimally perturbs existing neural architectures during surgery. NeuroRoots enables high density single unit recording from the cerebellum in vitro and in vivo. NeuroRoots also reliably recorded action potentials in various brain regions for at least 7 weeks during behavioral experiments in freely-moving rats, without adjustment of electrode position. This minimally invasive axon-like implant design is an important step toward improving the integration and stability of brain-machine interfacing.

Highly stretchable dynamic hydrogels for soft multilayer electronics.

Recent progress in the development of synthetic polymer networks has enabled the next generation of hydrogel-based machines and devices. The ability to mimic the mechanical and electrical properties of human tissue gives great potential toward the fields of bioelectronics and soft robotics. However, fabricating hydrogel devices that display high ionic conductivity while maintaining high stretchability and softness remains unmet. Here, we synthesize supramolecular poly(ionic) networks, which display high stretchability (>1500%), compressibility (>90%), and rapid self-recovery (<30 s), while achieving ionic conductivities of up to 0.1 S cm -1. Dynamic cross-links give rise to inter-layer adhesion and a stable interface is formed on account of ultrahigh binding affinities (>1013 M-2). Superior adherence between layers enabled the fabrication of an intrinsically stretchable hydrogel power source, paving the way for the next generation of multi-layer tissue mimetic devices.

Subsurface Profiling of Ion Migration and Swelling in Conducting Polymer Actuators with Modulated Electrochemical Atomic Force Microscopy.

Understanding the dynamics of ion migration and volume change is crucial to studying the functionality and long-term stability of soft polymeric materials operating at liquid interfaces, but the subsurface characterization of swelling processes in these systems remains elusive. In this work, we address the issue using modulated electrochemical atomic force microscopy as a depth-sensitive technique to study electroswelling effects in the high-performance actuator material polypyrrole doped with dodecylbenzenesulfonate (Ppy:DBS). We perform multidimensional measurements combining local electroswelling and electrochemical impedance spectroscopies on microstructured Ppy:DBS actuators. We interpret charge accumulation in the polymeric matrix with a quantitative model, giving access to both the spatiotemporal dynamics of ion migration and the distribution of electroswelling in the electroactive polymer layer. The findings demonstrate a nonuniform distribution of the effective ionic volume in the Ppy:DBS layer depending on the film morphology and redox state. Our findings indicate that the highly efficient actuation performance of Ppy:DBS is caused by rearrangements of the polymer microstructure induced by charge accumulation in the soft polymeric matrix, increasing the effective ionic volume in the bulk of the electroactive film for up to two times the value measured in free water.

Origami-inspired soft fluidic actuation for minimally invasive large-area electrocorticography.

Electrocorticography is an established neural interfacing technique wherein an array of electrodes enables large-area recording from the cortical surface. Electrocorticography is commonly used for seizure mapping however the implantation of large-area electrocorticography arrays is a highly invasive procedure, requiring a craniotomy larger than the implant area to place the device. In this work, flexible thin-film electrode arrays are combined with concepts from soft robotics, to realize a large-area electrocorticography device that can change shape via integrated fluidic actuators. We show that the 32-electrode device can be packaged using origami-inspired folding into a compressed state and implanted through a small burr-hole craniotomy, then expanded on the surface of the brain for large-area cortical coverage. The implantation, expansion, and recording functionality of the device is confirmed in-vitro and in porcine in-vivo models. The integration of shape actuation into neural implants provides a clinically viable pathway to realize large-area neural interfaces via minimally invasive surgical techniques.

Simple dynamic cell culture system reduces recording noise in microelectrode array recordings.

Microelectrode arrays (MEAs) have applications in drug discovery, toxicology, and basic research. They measure the electrophysiological response of tissue cultures to quantify changes upon exposure to biochemical stimuli. Unfortunately, manual addition of chemicals introduces significant noise in the recordings. Here, we report a simple-to-fabricate fluidic system that addresses this issue. We show that cell cultures can be successfully established in the fluidic compartment under continuous flow conditions and that the addition of chemicals introduces minimal noise in the recordings. This dynamic cell culture system represents an improvement over traditional tissue culture wells used in MEAs, facilitating electrophysiology measurements.