Electrochemical aptamer-based sensor for cerebrospinal fluid detection

Abstract

Cerebrospinal fluid (CSF) leakage is a serious medical condition that, if left undiagnosed or untreated, can lead to severe complications, including life-threatening intracranial infections (e.g., meningitis). Current diagnostic methods rely on immunofixation electrophoresis or nephelometry for detecting beta-2 transferrin or beta-trace protein, respectively, but these techniques are time-consuming, require specialized laboratory equipment, and may yield false-negative results due to sample contamination. To address these limitations, we developed a novel electrochemical aptamer-based (E-AB) biosensor for rapid, sensitive, and point-of-care detection of CSF leaks. The biosensor provides a conformation-switching aptamer system, building on our prior work through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX), to enable a “switch-off” mechanism upon target binding. This electrochemical transduction strategy facilitates reagent-free, real-time detection with a response time as short as 20 minutes. The sensor was optimized through square wave voltammetry (SWV) to achieve high specificity and signal suppression in CSF samples. Notably, the E-AB sensor demonstrated significant differentiation between CSF and serum, minimizing interference from blood contamination – a common issue in clinical sample collection. By streamlining the transition from aptamer discovery to biosensor development, this platform not only enhances the diagnostic workflow for CSF leaks but also establishes a versatile framework for future biosensing applications in neurology and emergency medicine. Further optimization and adaptation to portable electrochemical systems could position this technology as a clinically viable, point-of-care diagnostic tool for rapid CSF leak detection.