title: Cascade Signal Amplification Based on Copper Nanoparticle-Reported Rolling Circle Amplification for Ultrasensitive Electrochemical Detection of the Prostate Cancer Biomarker.
abstract: An ultrasensitive and highly selective electrochemical assay was first attempted by combining the rolling circle amplification (RCA) reaction with poly(thymine)-templated copper nanoparticles (CuNPs) for cascade signal amplification. As proof of concept, prostate specific antigen (PSA) was selected as a model target. Using a gold nanoparticle (AuNP) as a carrier, we synthesized the primer-AuNP-aptamer bioconjugate for signal amplification by increasing the primer/aptamer ratio. The specific construction of primer-AuNP-aptamer/PSA/anti-PSA sandwich structure triggered the effective RCA reaction, in which thousands of tandem poly(thymine) repeats were generated and directly served as the specific templates for the subsequent CuNP formation. The signal readout was easily achieved by dissolving the RCA product-templated CuNPs and detecting the released copper ions with differential pulse stripping voltammetry. Because of the designed cascade signal amplification strategy, the newly developed method achieved a linear range of 0.05-500 fg/mL, with a remarkable detection limit of 0.020 ± 0.001 fg/mL PSA. Finally, the feasibility of the developed method for practical application was investigated by analyzing PSA in the real clinical human serum samples. The ultrasensitivity, specificity, convenience, and capability for analyzing the clinical samples demonstrate that this method has great potential for practical disease diagnosis applications.
authors.affiliation: Key Laboratory of Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering, Shandong University , Jinan 250100, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Qilu Hospital, Shandong University , Jinan 250012, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering, Shandong University , Jinan 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering, Shandong University , Jinan 250100, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D003300:Copper / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods*; D004587:Electrophoresis, Agar Gel; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D003300:Copper; D017430:Prostate-Specific Antigen
keywords: electrochemical detection; poly(thymine)-templated copper nanoparticle; prostate specific antigen; rolling circle amplification; signal amplification