Cortical Response to Acute Implantation of the Utah Optrode Array in Macaque Cortex

Optogenetics has transformed neural circuit studies, but its application to large‐brained species like non‐human primates (NHPs) remains limited. A major challenge in NHP optogenetics is delivering light to large volumes of deep neural tissue with high spatiotemporal precision, without affecting superficial tissue. To overcome these limitations, we recently developed and tested in vivo in NHP cortex, the Utah Optrode Array (UOA). This is a 10 × 10 array of penetrating glass shanks, tiling a 4 × 4 mm ² area, bonded to interleaved needle‐aligned and interstitial µLED arrays, enabling independent photostimulation of deep and superficial tissue. Here, the acute biological response to UOA implantation in NHP cortex is investigated, to optimize device design for reduced insertion trauma and chronic response. To this goal, UOA shank diameter, geometry, and insertion pressure are varied, and their effects   on astrocytes, microglia, and neuronal viability are assessed, following acute implantation. It is found that UOAs with smaller shank diameter, smooth surface texture, and round tips cause the least damage. Higher insertion pressures have limited effects on inflammation, but cause greater tissue compression. The results highlight the importance of balancing shank diameter, geometry, and insertion pressure in UOA design for preserving tissue integrity and improving long‐term UOA performance and biocompatibility.