A paper-based label-free plasmonic nanosensor for portable pre-diagnosis of multiple metabolic diseases

Early diagnosis is crucial for improving the prognosis of patients with metabolic diseases. In this study, we developed an innovative, multiplexed, and user-friendly paper-based plasmonic nanosensor by integrating previously established FeHOAuC (Fe²⁺-catalyzed H₂O₂ prevents the aggregation of AuNPs by oxidizing cysteine) label-free plasmonic nanosensor. Initially, we prepared a paper art with designated sampling and colorimetric sections by applying polydimethylsiloxane onto cellulose and nitrocellulose papers. Subsequently, we fabricated and optimized the oxidase-coupled FeHOAuC system on the paper platform. The proposed nanosensor's sensitivity, specificity, and feasibility were evaluated using a quantitative color algorithm. In this sensor, pre-loaded oxidases convert target analytes into H₂O₂, which subsequently induces a color change in AuNPs by oxidizing cysteine under the catalytic action of Fe²⁺. This paper-based sensor can quantitatively measure glucose, cholesterol, uric acid, and lactate within 40 min. The limit of detection of 5-10 μM, combined with its demonstrated specificity, makes it highly suitable for the early diagnosis of related metabolic diseases. Importantly, through a straightforward dropping procedure and a smartphone camera, the plasmonic nanosensor can distinguish disease-related small molecules in real serum samples. In conclusion, the proposed paper-based plasmonic nanosensor device exhibited favorable performance with simple operation, presenting significant potential for domiciliary early diagnosis of multiple metabolic diseases.