A clinically integrated, frameless human Neuropixels workflow

High-density electrophysiological recording with Neuropixels probes enables single-unit resolution of human neural activity, but integration into routine clinical environments remains challenging and reported recordings have been limited to a few US centres. Here, we present a reproducible roadmap for human Neuropixels recordings under a nationally managed regulatory framework in the United Kingdom. Guided by the IDEAL Stage 2a (Development) framework, we established a frameless intraoperative workflow using manufacturer-sterilised probes and a commercially available, clinical-grade setup. We prospectively evaluated this workflow in six participants (mean age 62.5 years) undergoing elective ventriculoperitoneal shunt surgery, assessed across three predefined endpoints: clinical safety, procedural timing, and neural data yield. Iterative failure-mitigation cycles resolved key technical barriers, including neuronavigation interference and hardware instability. The workflow achieved zero research-related adverse events, maintained a 30-minute procedural extension, and progressively increased single-unit yield to 146 manually curated units.