Highly Sensitive Host-embedded Supramolecular Colorimetric Trimethylamine N-Oxide Sensor in Urine and Serum Environment

Trimethylamine N-oxide (TMAO) a crucial biomarker associated with the cardiovascular diseases (CVD), one of the common causes for worldwide deaths, thereby necessitating its accurate quantification in biological fluids for early diagnosis and disease management. Herein, for the first time a water-soluble supramolecular probe based on a host–guest chemistry between cucurbit[6]uril (CB6) and a styrylpyridine derivative (Spy), referred as Spy@CB6, was used for the colorimetric detection of TMAO in physiologically relevant matrices, including urine and human serum. The Spy@CB6 complex functions through an indicator displacement assay (IDA) mechanism, wherein TMAO efficiently displaces the Spy dye from their host-guest complexes by forming a stronger inclusion complex with CB6, resulting in distinct optical changes. This binding event enables highly sensitive detection, with low limit of detection (LOD) of 28.7 nM in urine and 7.4 nM in human serum, within clinically relevant ranges. The probe exhibits remarkable selectivity toward TMAO over ten common biological interferents and further demonstrates solid-state colorimetric responsiveness in urinated samples, highlighting its potential for point-of-care diagnostics. This work sets a new benchmark for highly sensitive TMAO detection in real biological matrices within clinically relevant concentration ranges and represents a significant advancement toward non-invasive, accessible, and patient-friendly diagnostic platforms.