Metal–Organic Framework-Functionalized Paper-Based Electrochemical Biosensor for Ultrasensitive Exosome Assay

The exosome has emerged as a promising noninvasive biomarker for the early diagnosis of cancer. Therefore, it is highly desirable to develop simple, inexpensive, and user-friendly biosensors for convenient, sensitive, and quantitative exosome assay. Herein, we developed a simple and cost-efficient electrochemical biosensor by combining a metal-organic framework (MOF)-functionalized paper and a screen-printed electrode (SPE) for portable, ultrasensitive, and quantitative determination of cancer-derived exosomes. In principle, the biosensor relied on recognition of the exosome by Zr-MOFs and aptamer to initiate the hybridization chain reaction (HCR) and the formation of DNAzyme for signal amplification. Benefiting from the high signal amplification ability of HCR, the label-free paper-based biosensor is capable of ultrasensitive exosome assay with a detection limit down to 5 × 103 particles/mL, which is superior to that of most reported methods. Moreover, the proposed paper-based biosensor possessed the advantages of low cost, simple operation, and high sensitivity, making it affordable and deliverable for point-of-care (POC) diagnosis in resource-limited settings.