Electrochemistry-empowered nano-labeling for versatile aptamer-based biosensing of tumor-associated proteins

Aptamer-based biosensing methods, despite achieving advancements in the detection of tumor-associated proteins, are only effective for a limited number of specific proteins and thus have restricted clinical value. This is mainly attributed to the requirement of prior knowledge and precise modulation of the aptamer structure, or the special spatial distribution of multiple binding sites in the target protein molecule. To address this limitation, we here report a new electrochemical method for aptamer-based biosensing of tumor-associated proteins. This method utilizes a universal signal transduction module (i.e., electrochemistry-empowered nano-labeling) that depends on the electrochemical protein bioconjugation at natural tyrosine residues and incorporates electroactive quantum dots to produce considerable signals. Consequently, this method neither relies on the particular structure or design of the aptamer nor necessitates the presence of distinct binding sites in protein molecules, affording excellent broad-spectrum applicability for protein detection. Validation with mucin 1, carcinoembryonic antigen, and alpha-fetoprotein has evidenced this method’s good sensitivity with a detection limit of 0.41 pg/mL, as well as its practicality in clinical samples and versatility in detecting different proteins. Moreover, this method can be readily accommodated to detect specific tumor cells, exhibiting excellent scalability. As such, this method holds great potential to be a user-friendly and widely applicable tool for detecting tumor-associated proteins and may offer new insights into the use of aptamers in biosensing applications.