Studies of neural pathways that contribute to loss and recovery of function following paralyzing spinal cord injury require devices for modulating and recording electrophysiological activity in specific neurons. These devices must be sufficiently flexible to match the low elastic modulus of neural tissue and to withstand repeated strains experienced by the spinal cord during normal movement. We report flexible, stretchable probes consisting of thermally drawn polymer fibers coated with micrometer-thick conductive meshes of silver nanowires. These hybrid probes maintain low optical transmission losses in the visible range and impedance suitable for extracellular recording under strains exceeding those occurring in mammalian spinal cords. Evaluation in freely moving mice confirms the ability of these probes to record endogenous electrophysiological activity in the spinal cord. Simultaneous stimulation and recording is demonstrated in transgenic mice expressing channelrhodopsin 2, where optical excitation evokes electromyographic activity and hindlimb movement correlated to local field potentials measured in the spinal cord.

Despite recent advances in microfabrication and nanofabrication, integrating multiple modes of communication with the brain into a single biocompatible neural probe remains a challenge. These multifunctional neural probes may further our understanding of normal and disrupted functions of neural circuits manifested in neurological conditions, such as Parkinson’s disease. Here, we present a novel family of probes fabricated using a thermal drawing process. In this process, a macroscopic template (preform) containing the desired features is drawn by applying heat and tension into a fiber that conserves the original geometry of the preform but at a much smaller scale. Being composed of soft materials, such as polymers, conductive composites, and low melting temperature metals, fiber based neural probes minimize the damage to the surrounding tissue when implanted. Furthermore, fiber drawing enables straightforward integration features allowing for simultaneous electrical, optical and chemical interrogation of the brain. We demonstrate the utility of these probes for one-step optogenetics, in which a viral vector carrying opsin genes is injected through the same device then used to optically stimulate neurons and record their response as electrical activity. With these probes, we also show, for the first time, recordings of electrical activity in the spinal cord of freely moving mice.

Stretchable optoelectronic fibers interrogate spinal cord circuits during free behavior. Studies of neural pathways that contribute to loss and recovery of function following paralyzing spinal cord injury require devices for modulating and recording electrophysiological activity in specific neurons. These devices must be sufficiently flexible to match the low elastic modulus of neural tissue and to withstand repeated strains experienced by the spinal cord during normal movement. We report flexible, stretchable probes consisting of thermally drawn polymer fibers coated with micrometer-thick conductive meshes of silver nanowires. These hybrid probes maintain low optical transmission losses in the visible range and impedance suitable for extracellular recording under strains exceeding those occurring in mammalian spinal cords. Evaluation in freely moving mice confirms the ability of these probes to record endogenous electrophysiological activity in the spinal cord. Simultaneous stimulation and recording is demonstrated in transgenic mice expressing channelrhodopsin 2, where optical excitation evokes electromyographic activity and hindlimb movement correlated to local field potentials measured in the spinal cord.

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities in a single biocompatible platform remains a challenge. We developed a device composed of an optical waveguide, six electrodes and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes while providing collocated neural recording and optical stimulation. The miniature (<200 μm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity.

Brain function depends on simultaneous electrical, chemical and mechanical signaling at the cellular level. This multiplicity has confounded efforts to simultaneously measure or modulate these diverse signals in vivo. Here we present fiber probes that allow for simultaneous optical stimulation, neural recording and drug delivery in behaving mice with high resolution. These fibers are fabricated from polymers by means of a thermal drawing process that allows for the integration of multiple materials and interrogation modalities into neural probes. Mechanical, electrical, optical and microfluidic measurements revealed high flexibility and functionality of the probes under bending deformation. Long-term in vivo recordings, optogenetic stimulation, drug perturbation and analysis of tissue response confirmed that our probes can form stable brain-machine interfaces for at least 2 months. We expect that our multifunctional fibers will permit more detailed manipulation and analysis of neural circuits deep in the brain of behaving animals than achievable before.

With its diversity of signaling modalities: electrical, chemical and mechanical, nervous system poses demands of multimodality on neural interface technologies. Multimaterial fiber technology may enable minimally invasive multifunctional probing of the complexity of neural circuits.

On page 6594, polymer fibers are designed by P. Anikeeva and co-workers to mimic fibrous geometry of the nerves allow simultaneous optical stimulation and neural recording in the spinal cord. The cover picture illustrates the flexibility of the bifunctional neural probes and their ability to accommodate deformation due to the movement of vertebrae.

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

Restoration of motor and sensory functions in paralyzed patients requires the development of tools for simultaneous recording and stimulation of neural activity in the spinal cord. In addition to its complex neurophysiology, the spinal cord presents technical challenges stemming from its flexible fibrous structure and repeated elastic deformation during normal motion. To address these engineering constraints, we developed highly flexible fiber probes, consisting entirely of polymers, for combined optical stimulation and recording of neural activity. The fabricated fiber probes exhibit low‐loss light transmission even under repeated extreme bending deformations. Using our fiber probes, we demonstrate simultaneous recording and optogenetic stimulation of neural activity in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, optical stimulation of the spinal cord with the polymer fiber probes induces on‐demand limb movements that correlate with electromyographical (EMG) activity.

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation.

Quantifying naturally occurring strains in soft materials, such as those of the human body, requires strain gauges with equal or greater mechanical compliance. This manuscript reports materials and mechanics approaches are reported for an all‐elastomer strain measurement device with gauge factor as high as 29 and with Young's modulus that approaches that of the human epidermis. These systems use thin carbon‐black‐doped poly(dimethylsiloxane) (CB‐PDMS) for the strain gauges due to its high resistivity and strong dependence on strain, and thick carbon‐nanotube‐doped PDMS (CNT‐PDMS) for the interconnects due to its comparatively low resistivity and weak dependence on strain. Devices composed of molded, straight resistors of CB‐PDMS joined by serpentine‐shaped interconnects of CNT‐PDMS, both in a matrix substrate of PDMS, have electrical responses that depend almost entirely on the strain in the CB‐PDMS. Integrated structures of this type have Young's moduli of 244 kPa, which lies within the range of values for the human epidermis. Such sheets can be readily laminated on and form conformal contact to the human skin, with only modest mechanical constraints on natural motions. Strains measured in this mode on the wrist are between 11.2% and 22.6%.

Restoration of motor and sensory functions in paralyzed patients requires the development of tools for simultaneous recording and stimulation of neural activity in the spinal cord. In addition to its complex neurophysiology, the spinal cord presents technical challenges stemming from its flexible fibrous structure and repeated elastic deformation during normal motion. To address these engineering constraints, we developed highly flexible fiber probes, consisting entirely of polymers, for combined optical stimulation and recording of neural activity. The fabricated fiber probes exhibit low-loss light transmission even under repeated extreme bending deformations. Using our fiber probes, we demonstrate simultaneous recording and optogenetic stimulation of neural activity in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, optical stimulation of the spinal cord with the polymer fiber probes induces on-demand limb movements that correlate with electromyographical (EMG) activity.