SUMMARY In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally-invasive, untethered studies on freely behaving animals. Here we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (μ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally-invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.
A class of thin, lightweight, fl exible, near-fi eld communication (NFC) devices with ultraminiaturized format is introduced, and systematic investigations of the mechanics, radio frequency characteristics, and materials aspects associated with their optimized construction are presented. These systems allow advantages in mechanical strength, placement versatility, and minimized interfacial stresses compared to other NFC technologies and wearable electronics. Detailed experimental studies and theoretical modeling of the mechanical and electromagnetic properties of these systems establish understanding of the key design considerations. These concepts can apply to many other types of wireless communication systems including biosensors and electronic implants.
Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless μ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor μ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different μ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.wireless optogenetics | stretchable electronics | wireless power transmission | deep brain stimulation | antenna O ptogenetics exploits a toolbox of light-sensitive proteins for optical manipulation of neural networks as a powerful means for the study of circuit-level mechanisms that underlie psychiatric diseases (1-4). Canonical optogenetic experiments in the brain require cranial insertion of an optical fiber to illuminate a region of interest (5, 6). Although this approach permits simple behavior modeling, constraints in animal motion and alterations in natural behaviors due to fiber tethering and external fixation complicate use in chronic longitudinal models and in experiments that assess complex responses. Many of these limitations can be bypassed with optoelectronic technologies and wireless receivers, as recently demonstrated in optogenetic stimulation of the brain, the peripheral nerves, and the spinal cord (4, 7-13). Systems that offer soft, compliant mechanical properties and thin, fully implantable designs are particularly advantageous (7). These systems, however, have still not been optimized to fully take advantage of the power of combining mouse genetics/optogentics with long-term beha...
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