ABSTRACT Endotoxins, predominantly lipopolysaccharides (LPS) derived from the cell walls of Gram‐negative bacteria, represent a critical challenge in biopharmaceuticals, medical device manufacturing, and food safety. Current gold‐standard endotoxin detection relies on Limulus Amebocyte Lysate (LAL) reagents, yet this approach suffers from two limitations: unsustainable exploitation of Limulus (horseshoe crab) resources and vulnerability to non‐specific interference due to its turbidity‐based readout. Here, we developed a fiber‐optic Surface‐enhanced Raman scattering (SERS) probe that enables highly sensitive endotoxin detection with drastically reduced LAL consumption. The probe was fabricated by immobilizing silver‐coated gold nanostars onto the surface of a tapered‐cylinder optical fiber, which was then integrated into a microfluidic capillary. Its sensing mechanism is based on a competitive assay that captures the characteristic Raman “fingerprint” of LAL‐endotoxin interactions: endotoxins competitively inhibit the adsorption of LAL reagents onto the fiber surface, resulting in a quantifiable SERS signal. Experimental results demonstrate that the fiber‐optic SERS sensor detects ultra‐low endotoxin concentrations (100 µEU mL −1 ) using only 5 µL of LAL reagent, marking a substantial reduction compared to conventional LAL assays. Tests with serum samples demonstrated that the sensor can differentiate between healthy individuals and septic patients, further confirming its translational potential. This technology offers a cost‐effective, rapid, and efficient solution for biosafety monitoring, clinical diagnostics, and quality control in food and pharmaceutical industries, advancing sustainable and reliable endotoxin detection beyond the limitations of traditional LAL‐based methods.
Li et al. (2026) studied this question.