A clinically integrated, frameless human Neuropixels workflow

High-density electrophysiological recording using Neuropixels probes enables single-unit resolution of human neural activity. However, integrating these systems into clinical environments remains challenging. Reported human recordings have been limited to a few centres in the United States utilising variable regulatory, sterilisation and operative techniques. Here, we present human Neuropixels recordings under a nationally managed ethical and regulatory framework in the United Kingdom. We provide a reproducible roadmap to overcome regulatory and equipment constraints. Guided by the IDEAL Stage 2a (Development) framework, we established a frameless intraoperative workflow utilising manufacturer-sterilised probes and a commercially available, clinical-grade setup for Neuropixels insertion including micromanipulator and endoscope holder. We prospectively evaluated this workflow across six participants (mean age 62.5 years) undergoing elective ventriculoperitoneal shunt surgery. Iterative failure-mitigation cycles successfully resolved key technical barriers, including neuronavigation interference and hardware instability. Assessed across three predefined endpoints (clinical safety, procedural timing, and neural data yield), the workflow achieved zero research-related adverse events and maintained a strict 30-minute procedural extension. Progressive technical refinements increased single-unit yield from 25 units during early development to 146 manually curated units. This approach provides a scalable, clinically integrated workflow to safely perform high-density electrophysiology in routine neurosurgical environments.