Ca-Triggered pH-Response Sodium Alginate Hydrogel Precipitation for Amplified Sandwich-Type Impedimetric Immunosensor of Tumor Marker.

Signal amplification is of great significance in the ultrasensitive electrochemical impedimetric immunoassays for tumor marker detection. A cascaded signal amplification approach was designed using gold nanoparticle-CaCO microspheres (AuNP-CaCO) to trigger pH-responsive alginate hydrogel precipitation for sandwich-type impedimetric immunosensor. AuNP-CaCO exerts a large hindrance effect and can release Ca ions under weak acidic conditions, and thus can serve as a multifunctional label. The hindrance effect of AuNP-CaCO can significantly enhance the impedance response as the initial signal amplification. Then, part of CaCO dissolves under weak acid conditions and releases Ca, which can cross-link with alginate to generate an insoluble alginate hydrogel precipitate on the sensing interface, significantly increasing the impedance signal. The impedance signal can be further amplified by making the hydrogel negatively charged based on the pH-responsive surface charge properties of the alginate hydrogel. Benefiting from the cascaded signal amplification, this impedimetric immunosensor exhibits a linear range from 1.0 fg mL to 100 ng mL, an detection limit of 0.09 fg mL, and ultrahigh sensitivity of 973.01 Ω (lg(ng mL)) toward the assay of prostate specific antigen (PSA).