A ratiometric electrochemical sensor for multiplex detection of cancer biomarkers using bismuth as an internal reference and metal sulfide nanoparticles as signal tags

Ratiometric electrochemical sensors can provide a relatively accurate analysis of target analytes due to their self-calibration function. Herein, we report a simple ratiometric strategy for achieving the electrochemical detection of Cd(II), Hg(II), Pb(II) and Zn(II), as well as multiple cancer biomarkers by using metal sulfide nanoparticles as signal tags. A conductive polymer film of poly(2-amino terephthalic acid) (ATA) was electrochemically produced on a glassy carbon electrode (GCE) and doped with carbon nanotubes (CNTs) and mercaptosuccinic acid (MSA). Using Bi(III) as an enhancer and internal reference in anodic stripping voltammetry, the MSA-CNT-ATA/GCE exhibited sensitive and distinguishable voltammetric responses to Cd(II), Hg(II), Pb(II) and Zn(II), with detection limits of 0.13, 0.49, 0.16 and 0.089 μg L−1, respectively. By using CdS, HgS, PbS and ZnS labeled secondary antibodies as the signal tags, alpha-fetoprotein, carbohydrate antigen 19–9, carbohydrate antigen 125, and carcinoembryonic antigen were determined simultaneously according to the amounts of metal sulfide in the sandwich-type complexes, with detection limits of 0.11 pg mL−1, 0.68 mU mL−1, 1.4 mU mL−1 and 0.23 pg mL−1, respectively. This ratiometric approach has a wide scope in the electrochemical detection of heavy metal ions as well as immunoassays with metal ions serving as signal tags.