Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics

Abstract

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.

Materials and technologies for soft implantable neuroprostheses

“…Complemented by a wireless powering platform, sophisticated and miniaturized implants have already communicated with the brain of freely moving mice, delivering light and pharmacology for several weeks 117 . These results demonstrate the good tolerance of the host medium and potential for long-term studies, which are essential for the development and understanding of neurotherapies.…”

Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems

“…These systems are of interest because they can conform to the surfaces of biological systems in ways that enable important capabilities of relevance to both biomedical research and clinical practice. Examples include devices for continuous monitoring of health status through the skin (1)(2)(3)(4)(5)(6)(7)(8)(9), optical stimulation of targeted neural circuits in the brain (10)(11)(12)(13), and electrophysiological mapping on the epicardial surface (14)(15)(16)(17). These platforms are unique because their lightweight construction, thin geometry, and low bending stiffness allow high-quality, minimally invasive interfaces to soft, dynamic biological tissues, in a manner that cannot be replicated with conventional wafer-based forms of electronics.…”

New Technologies for Elucidating Opioid Receptor Function

“…These approaches are powerful additions to the opioid receptor tool box in vitro , and perhaps could eventually be used for behavioral and systems level experiments in vivo . In vivo photopharmacology has been a significant challenge because delivery of UV light to deep brain structures, along with pharmacological infusion is technically challenging, although new wireless devices that can co-deliver light and drug simultaneously may be promising in this respect (73). In this recent report, delivery of opioids (DAMGO) was demonstrated using a microfluidic probe.…”