title: Fabrication of plasmon length-based surface enhanced Raman scattering for multiplex detection on microfluidic device.
abstract: The length of bioreceptors plays an important role in signal enhancement of surface-enhanced Raman scattering (SERS) due to amplification of electromagnetic fields generated by the excitation of localized surface plasmons. Herein, intact antibodies (IgG) and Fab fragments conjugated onto gold nanostar were used to fabricate two kinds of immunosensors for measurement of their SERS signals. Using CA125 as the antigen and Rhodamine-6G (R6G)-conjugated immunogolds, a SERS immunosensor was self-assembled by antigen-antibody interaction. The results showed that the SERS signal from the Fab immunosensor was 2.4 times higher than that of the IgG immunosensor. Furthermore, increased hot-spots by silver atom deposition onto the IgG and Fab immunosensor showed 2.1 and 1.4 times higher signals than before enhancement, respectively. For application, based on the Fab immunosensor, a SERS-compatible microfluidic system was designed for multiplex assays to overcome the drawbacks of conventional assays. This system can measure biological specimens directly from bio fluids instead of using a complex microfluidic device containing separation and detection elements. Four approved biomarkers of breast cancer, including cancer antigen (CA125), HER2, epididymis protein (HE4), and Eotaxin-1, were detected from patient-mimicked serum with limits of 15 fM, 17 fM, 21 fM, and 6.5 fM, respectively. The results indicated that the lengths and geometry of the bioreceptors determined the intensity of SERS signal from the interface and cavity of the sandwich immunosensor. Silver atom deposition at the cavity of the immunosensor increased the SERS signal. Finally, the SERS immunosensor built-in microfluidic system improved the performance of multiplex diagnostics.
authors.affiliation: Department of Chemical and Biological Engineering, Republic of Korea.
authors.forename: Anh H
authors.initials: AH
authors.lastname: Nguyen
authors.affiliation: Department of Chemical and Biological Engineering, Republic of Korea.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biological Engineering, Republic of Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Il Choi
authors.affiliation: Department of Chemical and Biological Engineering, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Seok Kwak
authors.affiliation: Department of Chemical and Biological Engineering, Republic of Korea; Green School, Korea University, Seoul 136-713, Republic of Korea. Electronic address: simsj@korea.ac.kr.
authors.forename: Sang
authors.initials: S
authors.lastname: Jun Sim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D045424:Complex Mixtures / Q000276:immunology; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D056656:Lab-On-A-Chip Devices; D046228:Microarray Analysis / Q000295:instrumentation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020349:Surface Plasmon Resonance / Q000295:instrumentation*
chemical_list: D014408:Biomarkers, Tumor; D045424:Complex Mixtures; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G
keywords: Cancer biomarkers; Microfluidics; Multiplex detection; Plasmonic nanoparticles; SERS