Fabrication, Characterization and In Vivo Validation of Flexible Optical Cortical Probe

Mechanically-flexible neurotechnologies based on soft and biocompatible organic materials have significant advances for neuroscience applications. However, integrating active electronic components into polymer-based neurotechnologies is still a challenge. This is particularly important for optogenetic applications where, despite important advances in light delivery technologies (such as optical fiber or inorganic µLED-based optoprobes) they mostly rely on rigid substrates. This is a key obstacle to their successful integration with neural tissue. In this work, we focus on the development of a novel optical cortical-probe (optoprobe), seamlessly integrating high performance inorganic µLEDs for optogenetic stimulation, along with organic electrodes for electrical recording. This optoprobe offers a plastic and conformable interface with the cortex. Here, we present our fabrication method for the integration of 4 µLEDs (100x100 µm, λ = 450 nm) and 4 PEDOT:PSS based electrodes (50x50 µm) and fully characterize the optoprobe for optogenetic stimulation and electrical recording. This includes analysis of the electrical crosstalk between the drive currents for the µLEDs and the electrical recording component (sensitive to 10s of microvolts). Driving the µLEDs can also increase the optoprobe’s temperature profile and influence the long-term stability of the optoprobe – both of these effects have been studied in accelerated testing. Furthermore, we show validation of the optoprobe performance in mouse auditory cortex <i>in vivo</i>. Integrating electrodes and µLEDs on a common transparent substrate has the potential to improve stimulation control by facilitating real-time adjustments based on observed neuronal responses through a closed-loop system. Moreover, our results demonstrate the scalability of this fabrication process to a large µLED arrays. This technology marks a significant step forward in the development of flexible optogenetic devices.