Supramolecular PDDA/PEDOT:PSS Biosensor for Early Pancreatic Cancer Detection via CA19-9: Clinical Validation on Human Blood Samples.

Pancreatic cancer has one of the highest mortality rates, and early detection remains a challenge, significantly limiting therapeutic strategies. In this study, we present the clinical validation of a novel multilayered capacitance-based biosensor for early pancreatic cancer detection. Poly-(diallyldimethylammonium chloride) and (poly-(3,4-ethylenedioxythiophene):polystyrenesulfonate) (PDDA/PEDOT:SS) were physically adsorbed onto gold interdigitated electrodes via self-assembly, followed by surface functionalization with CA19-9 antibodies. Upon selective binding of the CA19-9 biomarker, the adsorption kinetics indicated that the system reached equilibrium within 7 min. Polarization modulation infrared reflection absorption spectroscopy, atomic force microscopy analysis, and electrical measurements confirmed the successful functionalization of the biosensor surface. The interaction between CA19-9 and the functionalized surface was evaluated using electrical impedance spectroscopy. The calibration curve was best fitted to the Langmuir-Freundlich model, and all data sets were processed by visual analysis (IDMAP). Key characteristics of the devices  sensitivity and selectivity  demonstrate a limit of detection of 0.01 U/mL, limit of quantification of 0.03 U/mL, and specificity toward CA19-9. Analyses were conducted on 24 blood samples collected from patients at different stages of the disease. The good performance at low and moderate CA19-9 concentrations was supported by IDMAP and Bland-Altman statistical analysis. The results confirmed the biosensor's potential as an innovative, sensitive, and selective tool for early detection of pancreatic cancer, with the possibility of future technology transfer to the Brazilian Health System.