Ultra-flexible Electrodes Research Articles

High-Performance Stainless-Steel-Fiber-Reinforced Thick Ultra-flexible Electrode Applicable to 3D Free-Form Batteries

High-Performance Stainless-Steel-Fiber-Reinforced Thick Ultra-flexible Electrode Applicable to 3D Free-Form Batteries

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-μm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stableICMS in awake, behaving mouse models. Invivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.

Longitudinal neural and vascular recovery following ultraflexible neural electrode implantation in aged mice

Flexible neural electrodes improve the recording longevity and quality of individual neurons by promoting tissue-electrode integration. However, the intracortical implantation of flexible electrodes inevitably induces tissue damage. Understanding the longitudinal neural and vascular recovery following the intracortical implantation is critical for the ever-growing applications of flexible electrodes in both healthy and disordered brains. Aged animals are of particular interest because they play a key role in modeling neurological disorders, but their tissue-electrode interface remains mostly unstudied. Here we integrate in-vivo two-photon imaging and electrophysiological recording to determine the time-dependent neural and vascular dynamics after the implantation of ultraflexible neural electrodes in aged mice. We find heightened angiogenesis and vascular remodeling in the first two weeks after implantation, which coincides with the rapid increase in local field potentials and unit activities detected by electrophysiological recordings. Vascular remodeling in shallow cortical layers preceded that in deeper layers, which often lasted longer than the recovery of neural signals. By six weeks post-implantation vascular abnormalities had subsided, resulting in normal vasculature and microcirculation. Putative cell classification based on firing pattern and waveform shows similar recovery time courses in fast-spiking interneurons and pyramidal neurons. These results elucidate how structural damages and remodeling near implants affecting recording efficacy, and support the application of ultraflexible electrodes in aged animals at minimal perturbations to endogenous neurophysiology.

Ultraflexible electrode arrays for months-long high-density electrophysiological mapping of thousands of neurons in rodents.

Penetrating flexible electrode arrays can simultaneously record thousands of individual neurons in the brains of live animals. However, it has been challenging to spatially map and longitudinally monitor the dynamics of large three-dimensional neural networks. Here we show that optimized ultraflexible electrode arrays distributed across multiple cortical regions in head-fixed mice and in freely moving rats allow for months-long stable electrophysiological recording of several thousand neurons at densities of about 1,000 neural units per cubic millimetre. The chronic recordings enhanced decoding accuracy during optogenetic stimulation and enabled the detection of strongly coupled neuron pairs at the million-pair and millisecond scales, and thus the inference of patterns of directional information flow. Longitudinal and volumetric measurements of neural couplings may facilitate the study of large-scale neural circuits.

Chronic co-implantation of ultraflexible neural electrodes and a cranial window.

.Significance: Electrophysiological recording and optical imaging are two prevalent neurotechnologies with complementary strengths, the combined application of which can significantly improve our capacity in deciphering neural circuits. Flexible electrode arrays can support longitudinal optical imaging in the same brain region, but their mechanical flexibility makes surgical preparation challenging. Here, we provide a step-by-step protocol by which an ultraflexible nanoelectronic thread is co-implanted with a cranial window in a single surgery to enable chronic, dual-modal measurements.Aim: The method uses -thick polymer neural electrodes which conform to the site of implantation. The mechanical flexibility of the probe allows bending without breaking and enables long-lasting electrophysiological recordings of single-unit activities and concurrent, high-resolution optical imaging through the cranial window.Approach: The protocol describes methods and procedures to co-implant an ultraflexible electrode array and a glass cranial window in the mouse neocortex. The implantation strategy includes temporary attachment of flexible electrodes to a retractable tungsten-microwire insertion shuttle, craniotomy, stereotaxic insertion of the electrode array, skull fixation of the cranial window and electrode, and installation of a head plate.Results: The resultant implant allows simultaneous interrogation of brain activity both electrophysiologically and optically for several months. Importantly, a variety of optical imaging modalities, including wide-field fluorescent imaging, two-photon microscopy, and functional optical imaging, can be readily applied to the specific brain region where ultraflexible electrodes record from.Conclusions: The protocol describes a method for co-implantation of ultraflexible neural electrodes and a cranial window for chronic, multimodal measurements of brain activity in mice. Device preparation and surgical implantation are described in detail to guide the adaptation of these methods for other flexible neural implants and cranial windows.

Ultra-flexible light-permeable organic solar cells for the herbal photosynthetic growth

Ultra-flexible light-permeable organic solar cells (LP-OSCs) have attracted great attentions for their potential greenhouse applications. Herein, we reported for the first time the quantitative analysis of medicinal plants, photosynthetic efficiency and content of medicinal active ingredients, to evaluate the overall performance of the ultra-flexible OSC with high-transmission by simulating the greenhouse environment. In addition, ternary active layer strategy consisting of near-infrared (NIR) alloy acceptors was utilized for the LP-OSCs to effectively solve the trade-off between photovoltaic and optical properties. As a result, high efficiency of 15.1% and 12.04% for ultra-flexible opaque cell and devices with were obtained. The LP-OSCs based on ultra-flexible electrode with hierarchically photonic architectures had low incident light angle dependence which was beneficial for complex three-dimensional curved surface applications. Moreover, medicinal plants grown under ultra-flexible LP-OSCs displayed comparable growing tendency and pharmaceutical value with those grown under direct sunlight, which were studied based on the photosynthetic efficiency and content of medicinal active ingredients. This is the first report of the quantitative analysis of the effects of LP-OSCs on plant growth. Those results paved the way for realizing high-performing ultra-flexible LP-OSCs that could selectively absorb and transmit light for power generation and plants growth. The ultra-flexible semi-transparent OSCs with over 12% efficiency and 20% average visible light transmission were realized by using two constructive methods, ternary active layer strategy with an alloy-like NIR acceptor and ultra-flexible electrode with hierarchically photonic architectures. Most importantly, compared with growth under sunlight, medicinal plant showed a comparable growing tendency with similar content of medicinal active ingredients under ultra-flexible ST-OSCs as part of roofs in the simulated greenhouse, which unveiled the application of semi-transparent devices beyond photovoltaic as it could selectively absorb and transmit light for power generation and plants growth, respectively. • Achieved 15% opaque and 12% light-permeable ultra-flexible OSCs with the excellent mechanical stability. • The ultra-flexible light-permeable OSCs exhibits low incident light angle dependence. • The light-permeable OSCs can be simultaneously used for power-generation and photosynthesis.

Ice coating –A new method of brain device insertion to mitigate acute injuries

BackgroundReduction of insertion injury is likely important to approach physiological conditions in the vicinity of implanted devices intended to interface with the surrounding brain. New methodsWe have developed a novel, low-friction coating around frozen, gelatin embedded needles. By introducing a layer of thawing ice onto the gelatin, decreasing surface friction, we mitigate damage caused by the implantation. Results and comparison with existing methodsThe acute effects of a transient stab on neuronal density and glial reactions were assessed 1 and 7 days post stab in rat cortex and striatum both within and outside the insertion track using immunohistochemical staining. The addition of a coat of melting ice to the frozen gelatin embedded needles reduced the insertion force with around 50 %, substantially reduced the loss neurons (i.e. reduced neuronal void), and yielded near normal levels of astrocytes within the insertion track 1 day after insertion, as compared to gelatin coated probes of the same temperature without ice coating. There were negligible effects on glial reactions and neuronal density immediately outside the insertion track of both ice coated and cold gelatin embedded needles. This new method of implantation presents a considerable improvement compared to existing modes of device insertion. ConclusionsAcute brain injuries following insertion of e.g. ultra-flexible electrodes, can be reduced by providing an outer coat of ultra-slippery thawing ice. No adverse effect of lowered implant temperature was found, opening the possibility of locking fragile electrode construct configurations in frozen gelatin, prior to implantation into the brain.

A Ternary Fe1−xS@Porous Carbon Nanowires/Reduced Graphene Oxide Hybrid Film Electrode with Superior Volumetric and Gravimetric Capacities for Flexible Sodium Ion Batteries

AbstractSmart construction of ultraflexible electrodes with superior gravimetric and volumetric capacities is still challenging yet significant for sodium ion batteries (SIBs) toward wearable electronic devices. Herein, a hybrid film made of hierarchical Fe1−xS‐filled porous carbon nanowires/reduced graphene oxide (Fe1−xS@PCNWs/rGO) is synthesized through a facile assembly and sulfuration strategy. The resultant hybrid paper exhibits high flexibility and structural stability. The multidimensional paper architecture possesses several advantages, including rendering an efficient electron/ion transport network, buffering the volume expansion of Fe1−xS nanoparticles, mitigating the dissolution of polysulfides, and enabling superior kinetics toward efficient sodium storage. When evaluated as a self‐supporting anode for SIBs, the Fe1−xS@PCNWs/rGO paper electrode exhibits remarkable reversible capacities of 573–89 mAh g−1 over 100 consecutive cycles at 0.1 A g−1 with areal mass loadings of 0.9–11.2 mg cm−2 and high volumetric capacities of 424–180 mAh cm−3 in the current density range of 0.2–5 A g−1. More competitively, a SIB based on this flexible Fe1−xS@PCNWs/rGO anode demonstrates outstanding electrochemical properties, thus highlighting its enormous potential in versatile flexible and wearable applications.

Anisotropic etching in (3 1 1) Si to fabricate sharp resorbable polymer microneedles carrying neural electrode arrays

Polymer microneedles that get resorbed after insertion in the body have several interesting applications, for example in the insertion of ultra-flexible electrode arrays in neural tissue. In this work, we explore the use of molds created by etching in (3 1 1) silicon as a basis for the fabrication of such microneedles. Such molds can be etched anisotropically to much sharper angles compared to standard (1 0 0) silicon. It is demonstrated that sharp poly lactic-co-glycolic acid (PLGA) microneedles can be fabricated using the molds. It is also shown that by simple thermal bonding the fabricated PLGA microneedles can be combined with a ultra-flexible polyimide-based thin-film electrode array.

Chronic neural recording with probes of subcellular cross-section using 0.06 mm² dissolving microneedles as insertion device

Ultra-flexible electrode arrays with a cross-sectional area of only a few μm² show great promise for long-term, high resolution neural interfacing without detrimental scar tissue formation. However, due to their low stiffness, insertion is a challenge. In this work, we investigate microneedles consisting of quickly biodegradable, short-chained, acid terminated PLGA (50:50 lactide:glycolide ratio) as insertion device for a polyimide-based neural electrode array of 1 μm thickness. An upscalable, wafer-level fabrication process is presented. Both separate PLGA microneedles as well as complete, assembled neural probes were tested in vivo for up to 4 months. The arrays allowed to record spontaneous spike activity and evoked local field potentials in the somatosensory cortex of rats on all measured timepoints. Very limited lesion formation, measuring about 20% of the cross sectional area of the original microneedle, was observed. Neurons can be seen to infiltrate the area originally taken up by the dissolving PLGA microneedle. The results indicate that the presented electrode arrays and insertion method are well suitable for application in long-term, high resolution neural recording.

A textile-based SnO2 ultra-flexible electrode for lithium-ion batteries

The advancements in wearable electronic devices make it urgent to develop high-performance flexible lithium-ion batteries (LIBs) with excellent mechanical and electrochemical properties. Herein, we design a new 3D hierarchical hybrid sandwich flexible structure by anchoring SnO2 nanosheets (SnO2-NSs) on flexible carbon cloth and coating with thin amorphous carbon (AC) layer (CF@SnO2-NS@AC). The carbon cloth substrate works as the backbone and the current collector, while the thin AC layer provides extra support during the electrode expansion. The new architecture can be utilised as a binder-free electrode and presents extraordinary mechanical flexibility and outstanding electrical stability under external stresses. The new electrode can deliver a specific capacity as high as 968.6 mA h g−1 after 100 cycles at 85 mA g−1, which also shows remarkable rate capability and an excellent high current cycling stability. The outstanding electrochemical performances combined with the high mechanical flexibility and invariable electrical conductivity during/after different bending cycles make the new structure a promising oxide anode for flexible batteries. With the possibility of using a similar approach to design flexible cathode, the present work opens the door to empower the next-generation wearable devices and smart clothes with a robust and reliable battery.

Nanofabricated Ultraflexible Electrode Arrays for High-Density Intracortical Recording.

Understanding brain functions at the circuit level requires time‐resolved simultaneous measurement of a large number of densely distributed neurons, which remains a great challenge for current neural technologies. In particular, penetrating neural electrodes allow for recording from individual neurons at high temporal resolution, but often have larger dimensions than the biological matrix, which induces significant damage to brain tissues and therefore precludes the high implant density that is necessary for mapping large neuronal populations with full coverage. Here, it is demonstrated that nanofabricated ultraflexible electrode arrays with cross‐sectional areas as small as sub‐10 µm2 can overcome this physical limitation. In a mouse model, it is shown that these electrodes record action potentials with high signal‐to‐noise ratio; their dense arrays allow spatial oversampling; and their multiprobe implantation allows for interprobe spacing at 60 µm without eliciting chronic neuronal degeneration. These results present the possibility of minimizing tissue displacement by implanted ultraflexible electrodes for scalable, high‐density electrophysiological recording that is capable of complete neuronal circuitry mapping over chronic time scales.

Fluidic Microactuation of Flexible Electrodes for Neural Recording.

Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire scaffolds have expanded the family of ultraflexible microelectrodes that can bend and flex with the natural movement of the brain, reduce the inflammatory response, and improve the stability of long-term neural recordings. However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that temporarily increase the electrode size and stiffness thus aggravating neural damage during implantation, which can lead to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve. A method to deliver thin, ultraflexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultraflexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these "fluidic microdrives" allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the implantation site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultraflexible neural electrodes.

Ultraflexible nanoelectronic probes form reliable, glial scar-free neural integration.

Implanted brain electrodes construct the only means to electrically interface with individual neurons in vivo, but their recording efficacy and biocompatibility pose limitations on scientific and clinical applications. We showed that nanoelectronic thread (NET) electrodes with subcellular dimensions, ultraflexibility, and cellular surgical footprints form reliable, glial scar-free neural integration. We demonstrated that NET electrodes reliably detected and tracked individual units for months; their impedance, noise level, single-unit recording yield, and the signal amplitude remained stable during long-term implantation. In vivo two-photon imaging and postmortem histological analysis revealed seamless, subcellular integration of NET probes with the local cellular and vasculature networks, featuring fully recovered capillaries with an intact blood-brain barrier and complete absence of chronic neuronal degradation and glial scar.

Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers.

Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved.

An array of highly flexible electrodes with a tailored configuration locked by gelatin during implantation-initial evaluation in cortex cerebri of awake rats.

Background: A major challenge in the field of neural interfaces is to overcome the problem of poor stability of neuronal recordings, which impedes long-term studies of individual neurons in the brain. Conceivably, unstable recordings reflect relative movements between electrode and tissue. To address this challenge, we have developed a new ultra-flexible electrode array and evaluated its performance in awake non-restrained animals.Methods:An array of eight separated gold leads (4 × 10 μm), individually flexible in 3D, were cut from a gold sheet using laser milling and insulated with Parylene C. To provide structural support during implantation into rat cortex, the electrode array was embedded in a hard gelatin based material, which dissolves after implantation. Recordings were made during 3 weeks. At termination, the animals were perfused with fixative and frozen to prevent dislocation of the implanted electrodes. A thick slice of brain tissue, with the electrode array still in situ, was made transparent using methyl salicylate to evaluate the conformation of the implanted electrode array.Results: Median noise levels and signal/noise remained relatively stable during the 3 week observation period; 4.3–5.9 μV and 2.8–4.2, respectively. The spike amplitudes were often quite stable within recording sessions and for 15% of recordings where single-units were identified, the highest-SNR unit had an amplitude higher than 150 μV. In addition, high correlations (>0.96) between unit waveforms recorded at different time points were obtained for 58% of the electrode sites. The structure of the electrode array was well preserved 3 weeks after implantation.Conclusions: A new implantable multichannel neural interface, comprising electrodes individually flexible in 3D that retain its architecture and functionality after implantation has been developed. Since the new neural interface design is adaptable, it offers a versatile tool to explore the function of various brain structures.