An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications

Abstract

Objective: Optogenetics promises exciting neuroscience research by offering optical stimulation of neurons with unprecedented temporal resolution, cell-type specificity and the ability to excite as well as to silence neurons. This work provides the technical solution to deliver light to local neurons and record neural potentials, facilitating local circuit analysis and bridging the gap between optogenetics and neurophysiology research.

Approach: We have designed and obtained the first in vivo validation of a neural probe with monolithically integrated electrodes and waveguide. High spatial precision enables optical excitation of targeted neurons with minimal power and recording of single-units in dense cortical and subcortical regions.

Main results: The total coupling and transmission loss through the dielectric waveguide at 473 nm was 10.5 ± 1.9 dB, corresponding to an average output intensity of 9400 mW mm(-2) when coupled to a 7 mW optical fiber. Spontaneous field potentials and spiking activities of multiple Channelrhodopsin-2 expressing neurons were recorded in the hippocampus CA1 region of an anesthetized rat. Blue light stimulation at intensity of 51 mW mm(-2) induced robust spiking activities in the physiologically identified local populations.

Significance: This minimally invasive, complete monolithic integration provides unmatched spatial precision and scalability for future optogenetics studies at deep brain regions with high neuronal density.

Figure 1

Design of single shank, monolithically integrated probe: (a) 3D schematics of overall probe design. (b) Coupling junction between the optical fiber and the integrated waveguide. (c) A–A′ cross-section showing the waveguide with oxynitride core (purple) and oxide cladding (blue). (d) Simulation results of light intensity distribution as light propagates through the brain tissue.

Figure 2

Outline of fabrication steps with cross-sections along the long axis of the probe. (a) Deposition of bottom insulation layer on SOI wafer. (b) Patterning of electrical interconnections and electrodes. (c) Defining waveguide bottom cladding and core layers. (d) Deposition of top cladding layer and formation of electrical contacts. (e) Silicon DRIE for the optical fiber groove. (f) Final release of the complete probe.

Figure 3

Images of the released probe. (a) Relative size in contrast with a US quarter. (b) Microscope image of probe tip showing the lithographically defined electrode array and the waveguide. (c) SEM image of the waveguide magnified at the distal end. (d) SEM image of the waveguide at the proximal end and the optical fiber groove.

Figure 4

Fully packaged system with silicon probe bonded to the PCB and optical fiber aligned to the integrated waveguide. Light has been successfully guided from the laser source to the stimulation site.

Figure 5

In vivo recording from the CA1 pyramidal layer of a Long-Evans rat across eight recording channels (sites 1 and 8 correspond to the deepest and shallowest recording sites respectively). (a) Spontaneous local field potential and spiking activity. Each spiking event is marked and color-coded to represent a distinguishable single-unit. (b) Spiking activity recorded during a 25 Hz sinusoidal optical stimulation pattern. Two distinct single-units (pink and red) spiked robustly following the optical stimulation cycles. (c) Optical stimulation with square pulse waveforms (50 ms, 40 μW max power) showing distinct temporal relations between the light stimulus and spiking of the two units.