Fabrication of plasmon length-based surface enhanced Raman scattering for multiplex detection on microfluidic device

• Published in: Biosensors & bioelectronics Vol. 70; pp. 358 - 365
• Main Authors: Nguyen, Anh H., Lee, Jeewon, Il Choi, Hong, Seok Kwak, Ho, Jun Sim, Sang
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15-08-2015
• Subjects: Animals; Antigens; Biomarkers, Tumor - analysis; Biomarkers, Tumor - immunology; Cancer biomarkers; Complex Mixtures - immunology; Deposition; Devices; Equipment Design; Equipment Failure Analysis; Humans; Immunoassay - instrumentation; Immunoglobulin Fab Fragments - immunology; Immunoglobulin G - immunology; Immunosensors; Lab-On-A-Chip Devices; Microarray Analysis - instrumentation; Microfluidics; Multiplex detection; Multiplexing; Plasmonic nanoparticles; Raman scattering; Reproducibility of Results; Sensitivity and Specificity; SERS; Silver; Surface Plasmon Resonance - instrumentation; Cancer biomarkers; SERS; Multiplex detection; Microfluidics; Plasmonic nanoparticles
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2015.03.064

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 15fM, 17fM, 21fM, and 6.5fM, 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.
•Fabrication of plasmon length based SERS immunosensor based on IgG and Fab molecules.•Fab immunogold array showed sensitivity in integrated SERS-microfluidics device.•Increased hot spots numbers on the immunosensor surface in microfluidic device.•Detection for a panel of breast cancer biomarkers at ultralow concentration.