(38) Insertion of Neural Implants, GRIN Lenses, and Needles with Axial Ultrasonic Vibration Improves Study Outcomes

Introduction: A cornerstone of preclinical neuroscience research is modulation and measurement of neural activity using surgically-placed instruments like microelectrodes (electrophysiology), optics (fiber photometry), and needles (delivery of chemogenetic tools). However, acute and chronic tissue damage from these instruments continue to limit research, despite efforts to minimize damage through instrument optimization. An alternative approach is to optimize the insertion process; an ultrasonic-based inserter was investigated as a solution for a range of penetrating tools.

Methods: Using an ultrasonic inserter (NeuralGlider Inserter, Actuated Medical, Inc.), we investigated whether micron-scale vibration of electrodes, infusion needles, and optics during insertion reduced the force required to puncture brain tissue ex vivo and in vivo, and whether minimizing mechanical forces during surgery is sufficient to improve chronic measures of neural activity and reactive gliosis.

Results: Penetrating Neural Implants: Oscillation at 25kHz reduced the puncture force 70-80% into the pial surface of ex vivo rodent and porcine brains. In vivo, acute recordings from porcine cortex using silicon-based microelectrodes implanted with vibration demonstrated higher single unit yield compared to non-vibrated insertion controls, highlighting consequences of acute tissue damage caused during standard implantation. Vibrated insertion of small, high density, flexible electrodes (Neuropixels 1.0) enabled shuttle-free placement without buckling. The impact of insertion of implants perpendicular to the tissue surface compared to an angle is being investigated.
Optical Systems: Early results in ex vivo porcine brain tissue demonstrated that vibration reduced the puncture force of 0.5mm GRIN lenses (e.g., 50% reduction) and large diameter (e.g. 1.0 mm) optical lenses, resulting in decreased tissue compression compared to Control (p < 0.01, Student’s T-test). The goal is to eliminate the tissue coring typically required for optical lens placement. Planned imaging experiments in rodents will provide insight on tissue compression and damage at the optical lens-tissue interface in optics used for chronic optogenetic and neuroimaging modalities.
Delivery for Chemogenetics: Ex vivo testing demonstrated that infusion needle vibration reduced puncture force by >75% compared to control and enabled puncture of porcine dura with needles as small as 33G. In vivo testing showed that these smaller gauge infusion needles reduced aliquot backflow along needle tracks. Entrance and infusion sites also showed higher cellular density (less damage) with vibrated insertion after 6 weeks.

Conclusion: Controlled axial ultrasonic vibration of neuroscience tools during insertion improves placement and study outcomes and can advance research in three areas of neuroscience – Penetrating Neural Implants, Optical Systems, and Needles for Delivery of Chemogenetics.