Direct-Print-Enabled Customizable Neural Interfaces with Single-Cell and Single-Cell-Type Resolutions

Advanced silicon processing has enabled neural sensing or modulation at an unprecedentedly large scale and a spatial resolution matching that of the neuron density. However, most planar and rigid silicon electronics have limited access to regions within neural tissue, and it still remains challenging to scalably obtain high-density neural activities in 3D. There has been progress in bridging the geometrical gap between silicon electronics and neural tissues, but the demonstrated penetrating electrodes have low spatial density and their fabrication processes can damage sensitive silicon electronics.<br/>Here, we leveraged the state-of-the-art 2-photon polymerization technology to directly build high-density penetrating microelectrode arrays onto silicon electronics. We demonstrate with an array consisting of 6,600 electrodes pitched at 35 microns and with varying heights. The customizability of the process allows tailoring of array shape and spatial density to target different tissue shape or neuron density. As a proof-of-principle demonstration, we recorded retinal ganglion cell activities <i>ex vivo</i>, and were able to distinguish the neural activities with single-cell and single-cell-type resolution. We believe this technology will be crucial for next-generation neural interfaces that enable communication with neural circuits using their natural neural codes.