Multimodal layer-crossing interrogation of brain circuits enabled by microfluidic axialtrodes

Modulating and recording neuronal activity are essential for probing brain function and developing therapies for neurological disorders. However, conventional flat-end optical fibers—widely used for deep brain access— interact with neural tissue only at their distal tip, limiting spatial resolution across brain layers. To overcome this constraint, we introduce the microfluidic axialtrode: a soft, multimodal neural interface created by controllably angle-cleaving a thermally drawn, multimaterial optical fiber integrated with multiple metal electrodes and microfluidic channels. We demonstrate in vivo that this design enables spatially distributed optogenetics, multisite electrophysiological recording, and targeted drug delivery along the fiber’s axis, allowing simultaneous interaction with multiple neuronal layers. The axial configuration increases the functional interface with brain tissue, while the soft polymer construction and reduced cross-sectional footprint significantly suppress the inflammatory response compared to conventional silica fibers. Integration with a 3D-printed scaffold, fabricated from FDA-approved biocompatible resin, provides mechanical stability and compatibility with standard experimental hardware. The monolithic integration of these features positions the axialtrode as a scalable and versatile platform for next-generation neural interfacing.