Electrostatic Nanocage-Confined Probe for Electrochemical Detection of CA19-9 in Human Serum

Prompt and accurate detection of CA19-9 in human serum has great clinical significance for the early diagnosis and disease monitoring of cancer. Herein, we develop a convenient and antifouling electrochemical sensor for CA19-9 determination by immobilization of both an electrochemical redox probe [methylene blue (MB)] and immunorecognition element (CA19-9 antibody) on an electrostatic nanocage consisting of bipolar silica nanochannel array (bp-SNA). bp-SNA is composed of a negatively charged inner layer (n-SNA) and positively charged outer layer (p-SNA), which could be stably prepared on indium tin oxide (ITO) in several seconds using a two-step electrochemically assisted self-assembly approach and display asymmetric surface charges for confinement and enrichment of cationic MB into the inner n-SNA layer through electrostatic interaction. Modification of the CA19-9 antibody on the top surface of bp-SNA confers the sensing interface with specific recognition capacity. An antibody-antigen complex formed at the as-prepared immunosensor causes the decreased electrochemical signals of MB, achieving sensitive determination of CA19-9 with a wider linear dynamic range from 10 μU/mL to 50 U/mL and a low detection limit (3 μU/mL). Furthermore, accurate and feasible analysis of the CA19-9 amount in human serum samples by our proposed probe-integrated electrochemical immunosensor is realized.