Optogenetics allows rapid, temporally specific control of neuronal activity via targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose significant physical constraints on natural behaviors. In this report we bypass these limitations using novel technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliques that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain.

Summary Paragraph The fast-growing field of bioelectronic medicine aims to develop engineered systems that relieve clinical conditions through stimulation of the peripheral nervous system (PNS) 1 – 5 . Technologies of this type rely largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis/bladder pain syndrome 4 , 6 , 7 . Conventional, continuous stimulation protocols, however, cause discomfort and pain, particularly when treating symptoms that can be intermittent in nature (e.g. sudden urinary urgency) 8 . Direct physical coupling of electrodes to the nerve can lead to injury and inflammation 9 – 11 . Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. This paper introduces a miniaturized bio-optoelectronic implant that avoids these limitations, via the use of (1) an optical stimulation interface that exploits microscale inorganic light emitting diodes (μ-ILEDs) to activate opsins, (2) a soft, precision biophysical sensor system that allows continuous measurements of organ function, and (3) a control module and data analytics approach that allows coordinated, closed-loop operation of the system to eliminate pathological behaviors as they occur in real-time. In an example reported here, a soft strain gauge yields real-time information on bladder function. Data analytics algorithms identify pathological behavior, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalize bladder function in the context of acute cystitis. This all-optical scheme for neuromodulation offers chronic stability and the potential for cell-type-specific stimulation.

Summary In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable LEDs, with the ability to operate at wavelengths ranging from ultraviolet to blue, green/yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications.

We report on the fabrication of a biaxially stretchable array of high performance microsupercapacitors (MSCs) on a deformable substrate. The deformable substrate is designed to suppress local strain applied to active devices by locally implanting pieces of stiff polyethylene terephthalate (PET) films within the soft elastomer of Ecoflex. A strain suppressed region is formed on the top surface of the deformable substrate, below which PET films are implanted. Active devices placed within this region can be isolated from the strain. Analysis of strain distribution by finite element method confirms that the maximum strain applied to MSC in the strain suppressed region is smaller than 0.02%, while that on the Ecoflex film is larger than 250% under both uniaxial strain of 70% and biaxial strain of 50%. The all-solid-state planar MSCs, fabricated with layer-by-layer deposited multiwalled carbon nanotube electrodes and patterned ionogel electrolyte of poly(ethylene glycol) diacrylate and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide having high-potential windows, are dry-transferred onto the deformable substrate and electrically connected in series and parallel via embedded liquid metal interconnection and Ag nanowire contacts. Liquid metal interconnection, formed by injecting liquid metal into the microchannel embedded within the substrate, can endure severe strains and requires no additional encapsulation process. This formed MSC array exhibits high energy and power density of 25 mWh/cm(3) and 32 W/cm(3), and stable electrochemical performance up to 100% uniaxial and 50% biaxial stretching. The high output voltage of the MSC array is used to light micro-light-emitting diode (μ-LED) arrays, even under strain conditions. This work demonstrates the potential application of our stretchable MSC arrays to wearable and bioimplantable electronics with a self-powered system.

We report on the successful fabrication of stretchable microsupercapacitor (MSC) arrays on a deformable polymer substrate that exhibits high electrochemical performance even under mechanical deformation such as bending, twisting, and uniaxial strain of up to 40%. We designed the deformable substrate to minimize the strain on MSCs by adopting a heterogeneous structure consisting of stiff PDMS islands (on which MSCs are attached) and a soft thin film (mixture of Ecoflex and PDMS) between neighboring PDMS islands. Finite element method analysis of strain distribution showed that an almost negligible strain of 0.47% existed on the PDMS islands but a concentrated strain of 107% was present on the soft thin film area under a uniaxial strain of 40%. The use of an embedded interconnection of the liquid metal Galinstan helped simplify the fabrication and provided mechanical stability under deformation. Furthermore, double-sided integration of MSCs increased the capacitance to twice that of MSCs on a conventional planar deformable substrate. In this study, planar-type MSCs with layer-by-layer assembled hybrid thin film electrodes of MWNT/Mn3O4 and PVA-H3PO4 electrolyte were fabricated; when they are integrated into a circuit, these MSCs increase the output voltage beyond the potential of the electrolyte used. Therefore, various LEDs that require high voltages can be operated under a high uniaxial strain of 40% without any decrease in their brightness. The results obtained in this study demonstrate the high potential of our stretchable MSC arrays for their application as embedded stretchable energy storage devices in bioimplantable and future wearable nanoelectronics.