Multiwaveguide implantable probe for light delivery to sets of distributed brain targets

Abstract

Optical fibers are commonly inserted into living tissues such as the brain in order to deliver light to deep targets for neuroscientific and neuroengineering applications such as optogenetics, in which light is used to activate or silence neurons expressing specific photosensitive proteins. However, an optical fiber is limited to delivering light to a single target within the threedimensional structure of the brain. We here demonstrate a multi-waveguide probe capable of independently delivering light to multiple targets along the probe axis, thus enabling versatile optical control of sets of distributed brain targets. The 1.45 cm long probe is microfabricated in the form of a 360 micron-wide array of 12 parallel silicon oxynitride (SiON) multi-mode wave-guides clad with SiO 2 and coated with aluminum; probes of custom dimensions are easily created as well. The waveguide array accepts light from a set of sources at the input end, and guides the light down each waveguide to an aluminum corner mirror that efficiently deflects light away from the probe axis. Light losses at each stage are small (input coupling loss, 0.4 ± 0.3 dB; bend loss, negligible; propagation loss, 3.1 ± 1 dB/cm using the out-scattering method and 3.2 ± 0.4 dB/cm using the cut-back method; corner mirror loss, 1.5 ± 0.4 dB); a waveguide coupled, for example, to a 5 mW source will deliver over 1.5 mW to a target at a depth of 1 cm.The ability to deliver light into the brain for the purposes of controlling neural activity and other biological processes has opened up new frontiers in both basic neuroscience and neuroengineering. One arena of great activity is in the use of microbial opsins such as channelrhodopsin-2 [1], N. pharaonis halorhodopsin [2,3], and archaerhodopsin-3 [4] to make neurons activatable or silenceable by different colors of light, thus enabling assessment of the causal contribution of specific neurons, brain regions, or neural pathways to normal and abnormal behaviors and neural computations. To date, numerous in vivo studies have used optical fibers to deliver blue, yellow, or green laser light into brain targets in which certain neurons are expressing these opsins, but optical fibers can target just a single region. An implantable probe capable of delivering light to multiple points along the probe axis would enable more versatile optical control, opening up the ability to deliver patterned light to manipulate neural activity in different parts of a brain circuit in a systematic fashion, while greatly reducing surgical complexity and brain damage. We here describe the design and fabrication of a linear probe capable of multipoint independent light delivery, and find that this design enables the efficient delivery of light to multiple targets * Corresponding author: esb@media.mit.edu.OCIS codes: 170.0170, 130.2755, 130.3120, 130.3990, 230.3990, 230.7370 NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript along the probe axis, appropriate for delivering light to different lami...

Principles of designing interpretable optogenetic behavior experiments

“…As red light-sensitive molecules come into use Klapoetke et al 2014), in some species and contexts red light will incur less tissue absorption than blue or green, and thus incur less heating. If only a small section of tissue needs to be illuminated, the use of smaller light sources, lower light intensities, and/or shielding (e.g., in the form of beveled guide cannulas) could be used to limit light delivery to the targeted volume (Zorzos et al 2010;Tye et al 2011). Alternately, if a large area must be illuminated, strategies that can reduce unwanted heating include using larger fibers , fiber tips or lenses that spread light, or multiple light sources (Bernstein and Boyden 2011).…”

State-of-the-art MEMS and microsystem tools for brain research

“…Since then, engineering efforts have gradually evolved towards MEMS technologies for miniaturization, high-density integration, and precise definition of the probe dimensions with lithographic resolution. For example, MEMS dielectric waveguides fabricated on silicon substrates for stimulating the brain at multiple locations with blue and red light have been reported 160 . However, no recording electrodes were integrated on these devices; therefore, they could not support both optical stimulation and electrophysiology.…”

“…The lithographically defined waveguide has a precisely positioned stimulation site relative to the recording sites to provide the spatial resolution necessary for circuit mapping (Figure 4e). The waveguide can also be freely configured to guide light through different paths 164 or to have multiple stimulation sites 160,163 for specific application needs (Figure 4d). The probe shank dimensions are defined with micron resolution using a double-sided DRIE process on an SOI wafer.…”

“…A Matlab tool for predicting the tissue irradiance and the heat generated using different spatial and temporal light input was provided by Stujenske et al 170 . Despite these limitations, there is plenty of room for customizable illumination patterns given our control of numerical aperture, waveguide dimensions, and the addition of micromirrors 160,171 and diffusion elements. Photonic waveguides are commonly fabricated with micron dimensions, and thus, the number of independent light ports will increase rapidly, especially as the light sources are more efficiently packaged and coupled at the device backend.…”

Toward biomaterial-based implantable photonic devices

“…While optical waveguides based on silica fibers [128] or silicon oxynitride planar waveguides [129] in various forms have been implanted in animals, particularly for optogenetic studies in the brain [130], low-loss waveguides can be made from a variety of biocompatible, transparent materials. For low guiding loss, the refractive index of the biomaterial should be higher than that of adjacent tissues, which ranges typically from 1.34 (interstitial fluid) to 1.47.…”