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.

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 typehave 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%.

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 bioti-/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.

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 within a single biocompatible platform remains a challenge. Here, we introduce 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.

Stretchable optoelectronic fibers interrogate spinal cord circuits during free behavior.

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.flexible electronics | semiconductor nanomaterials | stretchable electronics | implantable biomedical devices | cardiac electrophysiology C ardiac arrhythmias occur in all component structures and 3D regions of the heart, resulting in significant challenges in diagnosis and treatment of precise anatomic targets (1). Many common arrhythmias, including atrial fibrillation and ventricular tachycardia, originate in endocardial substrates and then propagate in the transverse direction to affect epicardial regions (1, 2). Characterizing arrhythmogenic activity at specific regions of the heart is thus critical for establishing the basis for definitive therapies such as cardiac ablation (3). Advanced tools that offer sufficient spatial resolution (<1 mm) and intimate mechanical coupling with myocardial tissue, but without undue constraints on natural motions, would therefore be of great clinical importance (4-6). To date, cardiac ablation procedures have largely relied on point ablation catheters deployed in the endocardial space (1, 5, 7-9). Although successful in the treatment of simple arrhythmias originating in and around the pulmonary veins, these devices are poorly suited for treating complex arrhythmias, such as persistent atrial fibrillation (10-13), that arise from various sites inside the left atrium. Other classes of devices have demonstrated the utility of spatiotemporal voltage mapping using various modes of operation, including noninvasive surface mapping designs (14, 15), epicardial voltage-mapping "socks" (16-20), and endocardial contact and noncontact catheters, with densities approaching 64 electrodes (21-31). These solutions all exploit arrays of passive metal wirebased electrodes integrated on wearable vests and socks (14-20) or catheter systems (21-26) for mapping of complex arrhythmias. Building such mesh structures requires manual assembly and is only possible because the individual wires are millimeter scale in diameter and thus sufficiently large to be threaded to form a mesh.Fo...

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.

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