title: Sub-nanomolar detection of prostate-specific membrane antigen in synthetic urine by synergistic, dual-ligand phage.
abstract: The sensitive detection of cancer biomarkers in urine could revolutionize cancer diagnosis and treatment. Such detectors must be inexpensive, easy to interpret, and sensitive. This report describes a bioaffinity matrix of viruses integrated into PEDOT films for electrochemical sensing of prostate-specific membrane antigen (PSMA), a prostate cancer biomarker. High sensitivity to PSMA resulted from synergistic action by two different ligands to PSMA on the same phage particle. One ligand was genetically encoded, and the secondary recognition ligand was chemically synthesized to wrap around the phage. The dual ligands result in a bidentate binder with high-copy, dense ligand display for enhanced PSMA detection through a chelate-based avidity effect. Biosensing with virus-PEDOT films provides a 100 pM limit of detection for PSMA in synthetic urine without requiring enzymatic or other amplification.
authors.affiliation: Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
authors.forename: Kritika
authors.initials: K
authors.lastname: Mohan
authors.forename: Keith C
authors.initials: KC
authors.lastname: Donavan
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Arter
authors.forename: Reginald M
authors.initials: RM
authors.lastname: Penner
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Weiss
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000954:Antigens, Surface / Q000652:urine*; D001386:Azides / Q000737:chemistry; D001435:Bacteriophages / Q000737:chemistry / Q000235:genetics; D014408:Biomarkers, Tumor / Q000652:urine*; D015374:Biosensing Techniques / Q000379:methods*; D003500:Cyclization; D043425:Glutamate Carboxypeptidase II / Q000652:urine*; D006801:Humans; D008024:Ligands; D057230:Limit of Detection; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000652:urine*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000480:Alkynes; D000954:Antigens, Surface; D001386:Azides; D014408:Biomarkers, Tumor; D008024:Ligands; D013438:Sulfhydryl Compounds; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II