Visual electrophysiology measurements are important for ophthalmic diagnostic testing. Electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. Here we report the fabrication of soft graphene contact lens electrodes (GRACEs) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (ERG) from cynomolgus monkeys. The GRACEs give higher signal amplitude than conventional ERG electrodes in recordings of various full-field ERG responses. High-quality topographic mapping of multifocal ERG under simultaneous fundus monitoring is realized. A conformal and tight interface between the GRACEs and cornea is revealed. Neither corneal irritation nor abnormal behavior of the animals is observed after ERG measurements with GRACEs. Furthermore, spatially resolved ERG recordings on rabbits with graphene multi-electrode array reveal a stronger signal at the central cornea than the periphery. These results demonstrate the unique capabilities of the graphene-based electrodes for in vivo visual electrophysiology studies.

Simultaneous deep brain stimulation (DBS) and functional magnetic resonance imaging (fMRI) constitutes a powerful tool for elucidating brain functional connectivity, and exploring neuromodulatory mechanisms of DBS therapies. Previous DBS-fMRI studies could not provide full activation pattern maps due to poor MRI compatibility of the DBS electrodes, which caused obstruction of large brain areas on MRI scans. Here, we fabricate graphene fiber (GF) electrodes with high charge-injection-capacity and little-to-no MRI artifact at 9.4T. DBS-fMRI with GF electrodes at the subthalamic nucleus (STN) in Parkinsonian rats reveal robust blood-oxygenation-level-dependent responses along the basal ganglia-thalamocortical network in a frequency-dependent manner, with responses from some regions not previously detectable. This full map indicates that STN-DBS modulates both motor and non-motor pathways, possibly through orthodromic and antidromic signal propagation. With the capability for full, unbiased activation pattern mapping, DBS-fMRI using GF electrodes can provide important insights into DBS therapeutic mechanisms in various neurological disorders.

Soft and magnetic resonance imaging (MRI) compatible neural electrodes enable stable chronic electrophysiological measurements and anatomical or functional MRI studies of the entire brain without electrode interference with MRI images. These properties are important for many studies, ranging from a fundamental neurophysiological study of functional MRI signals to a chronic neuromodulatory effect investigation of therapeutic deep brain stimulation. Here we develop soft and MRI compatible neural electrodes using carbon nanotube (CNT) fibers with a diameter from 20 μm down to 5 μm. The CNT fiber electrodes demonstrate excellent interfacial electrochemical properties and greatly reduced MRI artifacts than PtIr electrodes under a 7.0 T MRI scanner. With a shuttle-assisted implantation strategy, we show that the soft CNT fiber electrodes can precisely target specific brain regions and record high-quality single-unit neural signals. Significantly, they are capable of continuously detecting and isolating single neuronal units from rats for up to 4−5 months without electrode repositioning, with greatly reduced brain inflammatory responses as compared to their stiff metal counterparts. In addition, we show that due to their high tensile strength, the CNT fiber electrodes can be retracted controllably postinsertion, which provides an effective and convenient way to do multidepth recording or potentially selecting cells with particular response properties. The chronic recording stability and MRI compatibility, together with their small size, provide the CNT fiber electrodes unique research capabilities for both basic and applied neuroscience studies.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Magnetic resonance imaging (MRI) compatible neural electrodes are important for combining high-resolution electrophysiological measurements with more global MRI mapping of brain activity, which is critical for fundamental neuroscience studies, as well as clinical evaluation and monitoring. Copper is a favorable material to use in MRI because it has magnetic susceptibility close to water and tissues. However, the cytotoxicity of copper precludes its direct implantation for neural recording. Here, we overcome this limitation by developing a graphene encapsulated copper (G-Cu) microelectrode. The toxicity of copper is largely eliminated, as evidenced by the in vitro cell tests and in vivo histology studies. Local field potentials and single-unit spikes were recorded from rodent brains with the G-Cu microelectrodes. Notably, the G-Cu microelectrodes show no image artifacts in a 7.0 T MRI scanner, indicating minimal magnetic field distortion in their vicinity. This high MRI compatibility of our G-Cu probes would open up new opportunities for fundamental brain activity studies and clinical applications requiring continuous MRI and electrophysiological recordings.

architecture, diversity, and electrophysiology of the human brain at early stages. [7,8] Brain organoids thus provide a reliable and easily accessible platform to study human brain development and neurodevelopmental diseases, [9][10][11][12] bridging the gap between animal research and human clinical study.However, long-term stable recording of single-cell electrophysiology in developing brain organoids is still a challenge. The recording technology not only needs to form minimally invasive and long-term stable electrical interfaces with individual neurons 3D distributed across brain organoids but also needs to accommodate the rapid volume change occurring during the organoid organogenesis and cortical expansion. Optical imaging coupled with fluorescence dyes [13] or calcium indicators [14] has been used to visualize the neuron activities in 3D. They, however, are limited by temporal resolution, penetration depth, and long-term signal stability. Electrical measurement techniques such as 2D multielectrode arrays (MEA) [15,16] and patch-clamp [17,18] have been applied to measure the functional development of brain organoids, but they can only capture the activities from the bottom surface of brain organoids [1,19,20] or assay one cell at a time with cell membrane disruption. The recent development of 3D bioelectronics enables 3D interfaces with brain organoids. [21][22][23][24][25][26][27] However, they either only contact organoids at the surface by flexible electronics, [21][22][23] where noncorrelated and 3D-distributed single-unit action potentials cannot be recorded, or penetrate organoids invasively by rigid probes, [25] which cannot further accommodate volume and morphological changes of brain organoids during development. It has also been shown that organoids can grow around a suspended array of electrodes, [26,27] but the electrodes cannot deform to adapt to the morphological changes of the organoid. To date, it is still a challenge to noninvasively probe neuron activity at single-cell, single-spike spatiotemporal resolution across the 3D volume of brain organoids, and over the time course of development. This constraint prevents further understanding of the functional development in brain organoids and standardizing culture conditions and protocols for brain organoid generation based on their electrical functions.Recently, we developed a cyborg organoid platform by integrating "tissue-like" stretchable mesh nanoelectronics with 2D stem cell sheets. Leveraging the 2D-to-3D reconfiguration Human induced pluripotent stem cell derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution of the electrical properties of brain organoids during development is currently limited by the measurement techniques, which cannot provide long-term stable 3D bioelectrical interfaces with developing brain organoids. Here, a cyborg brain organoid platform is reported, in which "tissue-like" stretchable mesh nanoelectronics are designed...

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