Exosomes derived from cancer cells have been recognized as a promising biomarker for minimally invasive liquid biopsy. Herein, a novel sandwich-type biosensor was fabricated for highly sensitive detection of exosomes. Amino-functionalized Fe₃O₄ nanoparticles were synthesized as a sensing interface with a large surface area and rapid enrichment capacity, while two-dimensional MXene nanosheets were used as signal amplifiers with excellent electrical properties. Specifically, CD63 aptamer attached Fe₃O₄ nanoprobes capture the target exosomes. MXene nanosheets modified with epithelial cell adhesion molecule (EpCAM) aptamer were tethered on the electrode surface to enhance the quantification of exosomes captured with the detection of remaining protein sites. With such a design, the proposed biosensor showed a wide linear range from 10² particles μL⁻¹ to 10⁷ particles μL⁻¹ for sensing 4T1 exosomes, with a low detection limit of 43 particles μL⁻¹. In addition, this sensing platform can determine four different tumor cell types (4T1, Hela, HepG2, and A549) using surface proteins corresponding to aptamers 1 and 2 (CD63 and EpCAM) and showcases good specificity in serum samples. These preliminary results demonstrate the feasibility of establishing a sensitive, accurate, and inexpensive electrochemical sensor for detecting exosome concentrations and species. Moreover, they provide a significant reference for exosome applications in clinical settings, such as liquid biopsy and early cancer diagnosis.

Exosomes have attracted increasing attention in the early diagnosis of tumors due to their participation in physiological and pathological processes. Herein, a novel label-free aptasensor based on the CuNi bimetallic metal–organic frameworks (MOFs) that was decorated with MXene quantum dots (MQDs) was fabricated for exosome sensing. The CuNi-MOFs functionalized with dual specific aptamers, CD63 and MUC1, served as an ideal nanocarrier and catalyst for efficient recognition and capture of target exosomes. Meanwhile, the MQDs with excellent electron transfer can promote the electrochemical catalytic performance of this designed aptasensor. It is noteworthy that the large specific surface area of 2D bimetallic CuNi-MOF nanosheets can offer plenty of exposed active sites and facilitate the connection of aptamers, thereby achieving the goal of specific capture and detection of exosomes. The as-prepared electrochemical aptasensor possesses a wide linear range of 1 × 10¹ to 1 × 10⁶ particles μL⁻¹ for exosome detection and a low detection limit of 5 particles μL⁻¹ (S/N = 3). Besides, the as-prepared aptasensor exhibited satisfactory electrochemical stability for the detection of exosomes, which can provide new ideas for clinical detection and tumor diagnosis.