To understand the brain functioning mechanisms, electrophysiological methods represent the most mature approach for recording brain dynamics at millisecond timescales in either local or large spatial scales. Microwire-based microelectrode arrays (MEAs) are a well-established tool for chronic recording of electrophysiologic signals and furthermore have the advantage of minimal brain damage if constructed from cellular-scale (4–100 μm neuron diameter) microwires. However, such cellular-scale MEAs are not widely used by neuroscientists, especially on deep insertion cases, due to the barrier of implantation. Efforts to reduce the size of microwires bring collateral difficulties due to buckling during penetration through membranes (dura/pia) and consequent inability to implant deeply into the brain or in a manner that leaves intact protective biolayers such as the dura mater. In this paper, we developed a custom skull cap with precision guide holes to stabilize the brain and dura, provide sufficient support to microwire along the insertion path, and minimize the unsupported length of microwire during dura penetration and deeper insertion. A cap matched to individual skull anatomy with offset for brain stabilization was designed based on computed tomography (CT) scan of the rat head and fabricated by stereolithography. Micro-milling and wax molding were conducted to fabricate precision insertion guide inside the cap. Animal surgical studies were conducted to test the performance of skull cap and insertion guide. Rats with skull cap attached had survived for multiple weeks until sacrificed by experimenters. Through a test cube with precision guide, a 25 μm diameter tungsten microwire penetrated through the dura mater and was manually inserted over 10 mm into the brain without buckling. In comparison, without the precision guide, insertion of the same microwire caused over 2 mm dimpling of the dura without penetration and finally led to wire buckling. Results showed that the custom skull cap with precision guide holes enabled the insertion of cellular-scale microwire electrodes deep into the brain through the dura mater without buckling.

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