A 3D multiwaveguide array for delivering light to multiple brain circuits

The ability to deliver light into the brain for the purpose of controlling neural activity or other biological processes, optogenetics, 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 channelrhodopsins, halorhodopsins, and archaerhodopsins to make neurons activatable or silenceable by light, thus enabling assessment of the causal contribution of specific neurons, brain regions, and neural pathways to normal and abnormal behaviors and neural computations. To date, numerous in vivo studies have used optical fibers, and fiber-electrode hybrids, to deliver visible light into brain targets in which neurons express opsins, but an optical fiber can target just a single region. An implantable probe capable of delivering light to arbitrary points in a 3-dimensional volume would enable more versatile optical control, opening up the ability to deliver patterned light to manipulate neural activity in distributed brain circuits.

Design, fabrication, and assembly of an implantable 3D waveguide array capable of independent light delivery to sets of neural targets in brain tissue. (a) Schematic showing the assembly procedure. (b) Photomicrographs of waveguide comb, baseplate holder, and alignment piece. Scale bar, 1 mm. (c) SEM micrograph of assembled 3D waveguide array with a zoomed-in view of the output apertures. Output apertures shown here are 9 μm × 30 μm. Scale bar, 100 μm.

The Boyden lab recently developed a linear probe comprising a set of integrated microwaveguides running in parallel to each other, microfabricated on a single substrate and capable of delivering light independently to multiple brain targets along the probe axis. In a paper published in Optics Letters, they now extend this design to the case of 3-dimensional light delivery to a set of targets distributed throughout the brain, by first fabricating waveguide combs containing many linear probes parallel to one another, then aligning multiple combs in a custom engineered baseplate for coupling to a digital micromirror device (DMD) for arbitrary light patterning. Each waveguide is about 10 microns x 10 microns wide, very small, and thus hundreds can be packed in the space occupied by a typical optical fiber. In addition, a 1024 x 768 pixel DMD, with a laser coupled, could easily enable the control of up to ~1000 points in 3-D space (even pooling many DMD mirrors, e.g. 800, per waveguide to increase power). The power out the end of the waveguide can be up to ~150 mW/mm^2, comparable to the highest powers used in optogenetics.

Optical systems for coupling light to 3D waveguide arrays. (a) Coupling method using a DMD chipset. (b) Coupling method using a scanning galvanometer. (c) Photomicrograph of 3D waveguide array showing an arbitrary illumination pattern using the DMD-based method. (d) Photomicrograph of the 3D waveguide array showing a DMD-mediated illumination pattern, “M-I-T”. Scale bar, 150 μm.

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