A Wireless Closed Loop System for Optogenetic Peripheral Neuromodulation

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.