Implantable photonic neural probes for light-sheet fluorescence brain imaging

Abstract

Significance: Light-sheet fluorescence microscopy is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. Here, we demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200 mm diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed and in vitro mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 μm for propagation distances up to 300 μm in free space. Imaging areas were as large as ≈ 240 μm x 490 μm in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of light-sheet fluorescence microscopy for deep brain imaging and experiments in freely-moving animals.

Plasmonics on a Neural Implant: Engineering Light–Matter Interactions on the Nonplanar Surface of Tapered Optical Fibers

“…The resonant collection of fluorescence with directional beamlets, whose angle depends on the spectral content, is an intriguing capability, which complements recent works that used diffractive elements to fabricate implantable probes for light‐sheet fluorescence imaging. [ 52 ] The plasmonic approach not only proves that this can be accomplished with a lossy material, but also allows using the zeroth order to impose or retrieve a spatial modulation, on the strength of the wavevector‐dependent momentum matching.…”

Cleanroom strategies for micro- and nano-fabricating flexible implantable neural electronics

“…In fact, a study performed by Sacher et al . [66] demonstrated that back grinding could be a suitable chip thinning method for photonic neural probes with a thickness ranging from 50–92 µm. In addition to this, there have been techniques explored to reduce mechanical damage to the chips caused by back grinding, such as the one explored by Morcom et al .…”

Development of nano- and microdevices for the next generation of biotechnology, wearables and miniaturized instrumentation

“…On this topic, focused on the importance of nano-optics for targeted biosignals in tissues and real samples, the development of implantable photonic neural probes for light-sheet fluorescence brain imaging has recently been reported. 69 This imaging approach was successfully achieved by the use of a miniaturized optical setup along with the incorporation of a probe with a propagation capability of distances up to 300 μm in free space using fluorescent optical responsive beads suspended in agarose as medium. The different steps involved in the design and several lithography and surface modification techniques should also be mentioned.…”