A wireless closed-loop system for optogenetic peripheral neuromodulation

Abstract

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.

Segment-Specific Optogenetic Stimulation inDrosophila melanogasterwith Linear Arrays of Organic Light-Emitting Diodes

“…37 On the other extreme, centimetre-sized light sources would be beneficial for delivering homogenous illumination to entire organs in vivo, e.g., for optogenetic control of bladder function. 38 OLEDs can also be stacked on top of each other, 39 to enable co-localized multi-colour optogenetic excitation. Further, they can made transparent, 40 which allows for simultaneous imaging through the light source.…”

Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency

“…Compared with other promising and more rapidly hydrolyzable PEG/IL-2 conjugates (e.g. NKTR-214 36 ), these findings are encouraging and could lead to future integration with wearable or implanted lightdelivery devices [37][38][39][40][41] which modulate drug activation. Consistent with other PEGylated cytokines, 36 we found that bioinspired, polymer-induced latency was able to prolong scIL-12 plasma circulation approximately 16-fold, potentially precluding the need for frequent, high dosing and improving tissue drug exposure in treatment settings.…”

Smart Sensing Systems Using Wearable Optoelectronics

“…In the early days of optogenetics, research was conducted to activate neurons in the brain, but recently its applications have been extended to the heart, bladder, and other tissues as well as the brain . Representatively, Mickle et al used resistive strain sensors to monitor bladder functions in real time and adopted optogenetic techniques for peripheral neuromodulation in the bladder via μLED . They reported that the optogenetic technique of applying light to neurons helped the bladder function normally.…”