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Straguzzi, J. N.

Publications and source records attributed to Straguzzi, J. N..

3 recordsLinked to original sources

Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery

Implantable silicon neural probes with integrated optical emitters and electrodes are emerging tools for simultaneous optogenetic stimulation and electrophysiological recording in deep brain regions. In parallel, neural probes with microfluidic channels have been developed for localized drug delivery and neurochemical sampling. However, thus far, such fluidic probes have lacked optical and electrical functionalities or been limited to a low number of optical emitters and/or electrodes, constraining their utility in multimodal investigations of neural circuits. Here, we introduce foundry-fabricated silicon nanophotonic neural probes with monolithically integrated microfluidics. Each probe has 16 silicon nitride grating coupler emitters, 18 titanium nitride microelectrodes, and one embedded microfluidic channel. We evaluate the photonic, electrophysiological, and microfluidic functionalities in vivo in optogenetic, blue-light-sensitive mice. With our multifunctional neural probes, we demonstrate local suppression of epileptic seizure activity (induced by microfluidic injection of 4-aminopyridine) using photostimulation. Through foundry-compatible microfluidics integration, this work advances the versatility of nanophotonic neural probes and presents new possibilities for multimodal neuroscience experiments leveraging this scalable neurotechnology.

neuroscience↗

Implantable nanophotonic neural probes for integrated patterned photostimulation and electrophysiology recording

Optogenetics has transformed neuroscience by allowing precise manipulation of neural circuits with light [1-5]. However, a central difficulty has been to deliver spatially shaped light and record deep within the brain without causing damage or significant heating. Current approaches form the light beam in free space and record the neural activity using fluorescence imaging or separately inserted electrodes [6-9], but attenuation limits optical penetration to around 1 mm of the brain surface [10]. Here, we overcome this challenge with foundry-fabricated implantable silicon neural probes that combine microelectrodes for electrophysiology recordings with nanophotonic circuits that emit light with engineered beam profiles and minimal thermal impact. Our experiments reveal that planar light sheets, emitted by our neural probes, excited more neurons and induced greater firing rate fatigue in layers V and VI of the motor and somatosensory cortex of Thy1-ChR2 mice at lower output intensities than low divergence beams. In the hippocampus of an epilepsy mouse model, we induced seizures, a network-wide response, with light sheets without exceeding the[~] 1{whitebullet}C limit for thermally induced electrophysiological responses [11-13]. These findings show that optical spatial profiles can be tailored for optogenetic stimulation paradigms and that the probes can photostimulate and record neural activity at single or population levels while minimizing thermal damage to brain tissue. The neural probes, made in a commercial silicon photonics foundry on 200-mm silicon wafers, demonstrate the manufacturability of the technology. The prospect of monolithically integrating additional well-established silicon photonics devices, such as wavelength and polarization multiplexers, temperature sensors, and optical power monitors, into the probes holds the potential of realizing more versatile, implantable tools for multimodal brain activity mapping.

bioengineering↗

Implantable photonic neural probes for light-sheet fluorescence brain imaging

SignificanceLight-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. AimMass 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. ApproachWe 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. ResultsThe probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 m for propagation distances up to 300 m in free space. Imaging areas were as large as {approx} 240 m x 490 m in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. ConclusionsThe neural probes can lead to new variants of light-sheet fluorescence microscopy for deep brain imaging and experiments in freely-moving animals.

bioengineering↗