Small form factor implantable neural probe with efficient flip chip µLED for in vivo optogenetics

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (µLEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate µLEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip µLEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm² but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm². Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 ºC. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.