How is flexible electronics advancing neuroscience research?

Innovative neurotechnology must be leveraged to experimentally answer the multitude of pressing questions in modern neuroscience. Driven by the desire to address the existing neuroscience problems with newly engineered tools, we discuss in this review the benefits of flexible electronics for neuroscience studies. We first introduce the concept and define the properties of flexible and stretchable electronics. We then categorize the four dimensions where flexible electronics meets the demands of modern neuroscience: chronic stability, interfacing multiple structures, multi-modal compatibility, and neuron-type-specific recording. Specifically, with the bending stiffness now approaching that of neural tissue, implanted flexible electronic devices produce little shear motion, minimizing chronic immune responses and enabling recording and stimulation for months, and even years. The unique mechanical properties of flexible electronics also allow for intimate conformation to the brain, the spinal cord, peripheral nerves, and the retina. Moreover, flexible electronics enables optogenetic stimulation, microfluidic drug delivery, and neural activity imaging during electrical stimulation and recording. Finally, flexible electronics can enable neuron-type identification through analysis of high-fidelity recorded action potentials facilitated by its seamless integration with the neural circuitry. We argue that flexible electronics will play an increasingly important role in neuroscience studies and neurological therapies via the fabrication of neuromorphic devices on flexible substrates and the development of enhanced methods of neuronal interpenetration.

Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

Optogenetics, which uses visible light to control the cells genetically modified with light-gated ion channels, is a powerful tool for precise deconstruction of neural circuitry with neuron-subtype specificity. However, due to limited tissue penetration of visible light, invasive craniotomy and intracranial implantation of tethered optical fibers are usually required for in vivo optogenetic modulation. Here we report mechanoluminescent nanoparticles that can act as local light sources in the brain when triggered by brain-penetrant focused ultrasound (FUS) through intact scalp and skull. Mechanoluminescent nanoparticles can be delivered into the blood circulation via i.v. injection, recharged by 400-nm photoexcitation light in superficial blood vessels during circulation, and turned on by FUS to emit 470-nm light repetitively in the intact brain for optogenetic stimulation. Unlike the conventional "outside-in" approaches of optogenetics with fiber implantation, our method provides an "inside-out" approach to deliver nanoscopic light emitters via the intrinsic circulatory system and switch them on and off at any time and location of interest in the brain without extravasation through a minimally invasive ultrasound interface.