Micro-fabricated implantable hybrid neural interfaces for optogenetics.

摘要

Neural interfaces are a direct communication pathway between nervous systems and external environment enabling promising clinical treatments for neurological disease and events such as spinal cord injury, stroke, and traumatic major amputations. Existing artificial neural interfaces mainly use electrical signals to evoke sensation in the central- and peripheral- nervous systems (CNS and PNS respectively), and these electrical systems have become a powerful tool for decades. However, its limitations demand improved technology. Recent developments in optogenetics have demonstrated the ability to target specific types of neurons with sub-millisecond temporal precision via direct optical stimulation of genetically modified neurons in the brain.;Current optogenetics-based stimulation interfaces mainly use laser- or light emitting diode (LED)-coupled optical fiber, micro-LEDs (mu-LEDs) array, and a laser beam focused through a microscope as their light sources. For experiments with freely behaving subjects, however, only limited light delivery methods are available. These systems' poor spatial resolution limits their functionality, and the tethered optical fiber greatly restricts subjects' natural behaviors.;To address these limitations, a series of hybrid neural interfaces based on a polymer-based flexible mu-LEDs array has been developed, and these arrays are designed to provide a unique solution to the current demand for multichannel, bi-directional neural interface devices. Depending on interface location, there are three different neural interfaces: Opto-muECoG array for epidural stimulation, three dimension (3-D) waveguide array for deep cortical stimulation, and slanted 3-D waveguide array for multi cortical layers stimulation. The Opto-muECoG array contains a transparent micro- electrocorticogram (muECoG) electrode array with integrated mu-LED bare dies. To further improve the spatial and depth resolutions of the optical stimulation via the mu-LED, two types of 3-D multi-LED arrays were developed by coupling micro-scale optical waveguides with LED chips using a polymer-based microfabrication technology. Integration of individually addressable mu-LED chips with varying-length microneedles enables precise light delivery to target neurons in specific cortical layers.;To demonstrate the wireless capability of the arrays, this author and colleagues proposed a wireless-powered, multichannel optrodes array that is capable of simultaneous light stimulation and electrical neural recording.;Based on the development of hybrid neural interfaces, an optogenetics-based cortical visual prosthesis has been designed for treating all forms of blindness. With the hybrid neural interfaces, the core hypothesis that epidural optical stimulation of microbial opsin expressing neurons in the primary visual cortex (V1) can induce phosphine, artificial visual sensation, and perception, has been tested.