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Abstract:
Optogenetics enables researchers to manipulate neural activity through wavelength-selective, cell-type specific excitation, inhibition, and modulation. Tools for delivering multicolor photostimulation to deep tissue targets with sufficient spatiotemporal resolution and optical power while maintaining a small form factor remain challenging to realize. Here, we demonstrate compact nanophotonic neural probes for blue and red photostimulation and electrophysiological recording. Neural probes with 6 mm long shanks, 26 TiN recording electrodes, and 26 pairs of SiN grating coupler emitters (emitter/electrode pitch: 188 µm; span: 4.80 mm) were designed and fabricated in a wafer-scale integrated photonic platform at Advanced Micro Foundry (AMF), Singapore. Devices were polished to achieve a shank thickness of 37 ± 18 µm (mean ± SD) (n=4 probes). Electrode impedances were reduced using laser surface roughening from a nominal impedance of 3.47 ± 0.15 MΩ (n=75 electrodes) to a final impedance of 0.32 ± 0.12 MΩ (n=90 electrodes). On-shank directional coupler filters enable compact wavelength demultiplexing of blue- (473 nm) and red- (638 nm) light to specially designed grating coupler emitters. Insertion loss for neural probes after packaging for blue- and red-light grating coupler emitters were measured as 27.1 ± 4.7 dB (n=64 emitters) and 29.5 ± 4.3 dB (n=64 emitters), respectively. Neural probes were connected to a custom dual-color laser scanning system (473 nm, 300mW; 638 nm, 180 mW) via a 16-core multicore fiber for photostimulation through 16 of 26 emitter pairs, with average emitter output powers up to 214 µW and 88 µW for blue- and red-light, respectively. We validated the neural probe functionalities by achieving selective blue-light induced inhibition in a VGAT-ChR2 mouse and selective red-light induced excitation in an Adora2a-Cre + AAV-flex-ChrimsonR mouse. Given its two emission wavelengths and long site span, this probe will facilitate experiments involving bidirectional circuit manipulations across both shallow and deep structures.
