title: Controlled Film Architectures to Detect a Biomarker for Pancreatic Cancer Using Impedance Spectroscopy.
abstract: The need for analytical devices for detecting cancer at early stages has motivated research into nanomaterials where synergy is sought to achieve high sensitivity and selectivity in low-cost biosensors. In this study, we developed a film architecture combining self-assembled monolayer (SAM) and layer-by-layer (LbL) films of polysaccharide chitosan and the protein concanavalin A, on which a layer of anti-CA19-9 antibody was adsorbed. Using impedance spectroscopy with this biosensor, we were capable of detecting low concentrations of the antigen CA19-9, an important biomarker for pancreatic cancer. The limit of detection of 0.69U/mL reached is sufficient for detecting pancreatic cancer at very early stages. The selectivity of the biosensor was inferred from a series of control experiments with samples of cell lines that were tested positive (HT29) and negative (SW620) for the biomarker CA19-9, in addition to the lack of changes in the capacitance value for other analytes and antigen that are not related to this type of cancer. The high sensitivity and selectivity are ascribed to the very specific antigen-antibody interaction, which was confirmed with PM-IRRAS and atomic force microscopy. Also significant is that used information visualization methods to show that different cell lines and commercial samples containing distinct concentrations of CA19-9 and other analytes can be easily distinguished from each other. These computational methods are generic and may be used in optimization procedures to tailor biosensors for specific purposes, as we demonstrated here by comparing the performance of two film architectures in which the concentration of chitosan was varied.
authors.affiliation: São Carlos Institute of Physics, University of São Paulo , 13560-970 São Carlos, São Paulo Brazil.|São Carlos School of Engineering, University of São Paulo , 13560-000 São Carlos, São Paulo, Brazil.
authors.forename: Andrey C
authors.initials: AC
authors.lastname: Soares
authors.affiliation: São Carlos Institute of Physics, University of São Paulo , 13560-970 São Carlos, São Paulo Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Soares
authors.affiliation: São Carlos Institute of Physics, University of São Paulo , 13560-970 São Carlos, São Paulo Brazil.
authors.forename: Flavio M
authors.initials: FM
authors.lastname: Shimizu
authors.affiliation: Barretos Cancer Hospital , 14784-400 Barretos, São Paulo, Brazil.
authors.forename: Matias E
authors.initials: ME
authors.lastname: Melendez
authors.affiliation: Barretos Cancer Hospital , 14784-400 Barretos, São Paulo, Brazil.
authors.forename: André L
authors.initials: AL
authors.lastname: Carvalho
authors.affiliation: São Carlos Institute of Physics, University of São Paulo , 13560-970 São Carlos, São Paulo Brazil.
authors.forename: Osvaldo N
authors.initials: ON
authors.lastname: Oliveira
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D003208:Concanavalin A / Q000737:chemistry; D058266:Dielectric Spectroscopy / Q000379:methods*; D025802:Electric Capacitance; D005227:Fatty Acids / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: C505222:11-mercaptoundecanoic acid; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D005227:Fatty Acids; D013438:Sulfhydryl Compounds; D003208:Concanavalin A; D006046:Gold; D048271:Chitosan
keywords: CA19−9; biosensors; impedance spectroscopy; information visualization; nanostructured films; pancreatic cancer