title: Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor.
abstract: Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10(-16) g ml(-1) in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10(-4).
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: P M
authors.initials: PM
authors.lastname: Kosaka
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Pini
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Ruz
authors.affiliation: 1] IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain [2] Instituto de Química, Universidade de Sao Paulo, Av. Prof. Lineu Prestes 748, 05508-900 Sao Paulo, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: da Silva
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: M U
authors.identifier: 0000000170120049
authors.initials: MU
authors.lastname: González
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Ramos
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: M
authors.identifier: 0000000324145725
authors.initials: M
authors.lastname: Calleja
authors.affiliation: IMM-Instituto de Microelectrónica de Madrid (CNM-CSIC), Isaac Newton 8, PTM, E-28760 Tres Cantos, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tamayo
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000097:blood*; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor