Slope Extrusion Microchannel Integrating Terahertz Meta-Sensor Embedded in Cerebrospinal Fluid for Precise Diagnosis of PCNSIs

Postoperative central nervous system infections (PCNSIs) are serious complications following craniotomy, for which prompt diagnosis and empirical antimicrobial treatment are critical to reducing comorbid complications and mortality. Clinically, PCNSIs and their severity are determined by the leukocyte concentration (<i>L</i>_c) and multinucleated cell/monocyte (MNC/MO) ratio in cerebrospinal fluid (CSF). However, traditional detection methods are time-consuming and unsuitable for rapid bedside use. Here, we propose a novel terahertz biosensor that integrates a metasurface with slope lateral extrusion technology, which shows a significant response to leukocytes in CSF while having minimal impact on other components, such as erythrocytes and proteins. This innovative sensor enables precise, rapid, and label-free detection of both <i>L</i>_c and MNC/MO ratio in complex liquid environments. Specifically, it can simultaneously quantify the <i>L</i>_c across a broad range (0-2000 × 10⁶/L) and the MNC/MO ratio by monitoring changes in resonance frequency and transmission intensity. Mechanistically, monocytes induce more pronounced changes in frequency and transmission intensity compared to multinucleated cells, a difference attributed to variations in dielectric constant caused by disparities in cell volume and nuclear-to-cytoplasmic (N/C) ratio. This innovative approach achieves, for the first time, accurate detection of components in complex body fluids. Validation using clinical CSF samples demonstrates its potential for reliable quantitative analysis, highlighting its significance for rapid bedside diagnosis and their severity of PCNSIs.