Spherical nucleic acids-based cascade signal amplification for highly sensitive detection of exosomes

Exosomes are regarded as a promising biomarker in the diagnosis of disease due to their close relationship with the change of physiology and pathology. However, it is still a hard challenge to come up with a highly sensitive method for the exosomes detection. Herein, we propose a spherical nucleic acids (SNAs)-based cascade signal amplification strategy for the exosomes detection with high sensitivity. In this method, SNAs anchoring on exosomes membrane can be extended to form polyT sequence by terminal deoxynucleotidyl transferase (TdT), generating a template strand for the Exo III-catalyzed excision of the designed signal probe (probe A), which may finally induce significant decrease of electrochemical signal due to the consumption of probe A. Benefiting from the SNAs-based cascade signal amplification, this fabricated biosensor achieves a limit of detection for exosomes as low as 44 particles/μL. Moreover, this method shows good performance in the differentiation of healthy and malignancy colorectal cancer patients. Therefore, without complicated nucleic acids sequences design, our approach provides a cascade signal amplification strategy for the highly sensitive detection of exosomes and shows the potential applications in clinical diagnosis.