One‐droplet saliva detection on photonic crystal‐based competitive immunoassay for precise diagnosis of migraine

Abstract Migraine exhibits a substantial prevalence worldwide. The current diagnostic criteria rests exclusively on clinical characteristics without any objective and reliable means. The calcitonin gene‐related peptide (CGRP), as a biomarker for distinguishing migraine, undergoes swift degradation, featuring a half‐life of under 10 min, which poses a significant challenge to the point‐of‐care testing of CGRP in clinical application. Here, a photonic crystal (PC)‐based biochip has been developed to detect CGRP via the fluorescence competition assay. The chip integrates the functionalities of fluorescence enhancement and hydrophilic–hydrophobic patterning enrichment, enabling rapid and sensitive detection of CGRP. After investigating the optimal enhancement distance of fluorescence near PCs, the chip allows CGRP detection using <30 μL of saliva at room temperature within 10 min. A minimum detection limit of 0.05 pg/mL is achieved. Furthermore, CGRP concentrations in the saliva of 70 subjects have been tested by PC biochips. The results exhibit strong concordance with the enzyme‐linked immunosorbent assay (ELISA), demonstrating a linear correlation coefficient of R 2 of 0.97. This sensitive detection of markers within such a short duration surpasses the capacities of ELISA, which paves the way for establishing a precise diagnostic framework integrating clinical phenotypes and biomarkers for migraine.