Sub-micrometric reflectometry for localized label-free biosensing

In this work we present an optical technique for characterizing sub-micrometric areas based on reflectivity of the light as a function of angle of incidence for the two pure polarizations s and p, covering a range of angles of incidence from -71.80 degrees to 71.80 degrees with a resolution of 0.1 degrees. Circular areas with a diameter in the order of 600 nm can be characterized, and the spectra for the two polarizations can be obtained with a single measurement. For biosensing purposes, we have fabricated several Bio Photonic Sensing Cells (BICELLs) consisting of interferometers of 1240 nm of SU-8 polymer over silicon. An indirect immunoassay is performed over these BICELLs and compared experimentally with FT-VIS-NIR spectrometry and theoretical calculations. The Limit of Detection (LoD) achieved is comparable with standard high resolution spectrometry, but with the capability of analyzing sub-micrometric domains for immunoassays reactions onto a sensing surface. (C) 2015 Optical Society of AmericaThis work has been partially funded under the projects under the projects PLATON (Ref: TEC2012-31145) and INNBIOD (Ref: IPT-2011-1429-01000) from the Ministerio de Economia y Competitividad (MINECO) of Spain. We acknowledge Nightingale-EOS and Stephen Morris for his contribution to the development of this optical tool.Casquel, R.; Soler, JA.; Holgado, M.; Lopez, A.; Lavin, A.; De Vicente, J.; Sanza, FJ.... (2015). Sub-micrometric reflectometry for localized label-free biosensing. Optics Express. 23(10):12544-12554. doi:10.1364/OE.23.012544S12544125542310Fan, X., White, I. M., Shopova, S. I., Zhu, H., Suter, J. D., & Sun, Y. (2008). Sensitive optical biosensors for unlabeled targets: A review. Analytica Chimica Acta, 620(1-2), 8-26. doi:10.1016/j.aca.2008.05.022Homola, J. (2008). Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species. Chemical Reviews, 108(2), 462-493. doi:10.1021/cr068107dBarrios, C. A., Bañuls, M. J., González-Pedro, V., Gylfason, K. B., Sánchez, B., Griol, A., … Casquel, R. (2008). Label-free optical biosensing with slot-waveguides. Optics Letters, 33(7), 708. doi:10.1364/ol.33.000708Estevez, M. C., Alvarez, M., & Lechuga, L. M. (2011). Integrated optical devices for lab-on-a-chip biosensing applications. Laser & Photonics Reviews, 6(4), 463-487. doi:10.1002/lpor.201100025Haes, A. J., & Van Duyne, R. P. (2002). A Nanoscale Optical Biosensor:  Sensitivity and Selectivity of an Approach Based on the Localized Surface Plasmon Resonance Spectroscopy of Triangular Silver Nanoparticles. Journal of the American Chemical Society, 124(35), 10596-10604. doi:10.1021/ja020393xKugel, V., & Ji, H.-F. (2014). Nanopillars for Sensing. Journal of Nanoscience and Nanotechnology, 14(9), 6469-6477. doi:10.1166/jnn.2014.9346Holgado, M., Barrios, C. A., Ortega, F. J., Sanza, F. J., Casquel, R., Laguna, M. F., … Maquieira, A. (2010). Label-free biosensing by means of periodic lattices of high aspect ratio SU-8 nano-pillars. Biosensors and Bioelectronics, 25(12), 2553-2558. doi:10.1016/j.bios.2010.04.042Holgado, M., Casquel, R., Sánchez, B., Molpeceres, C., Morales, M., & Ocaña, J. L. (2007). Optical characterization of extremely small volumes of liquid in sub-micro-holes by simultaneous reflectivity, ellipsometry and spectrometry. Optics Express, 15(20), 13318. doi:10.1364/oe.15.013318Rosencwaig, A., Opsal, J., Willenborg, D. L., Kelso, S. M., & Fanton, J. T. (1992). Beam profile reflectometry: A new technique for dielectric film measurements. Applied Physics Letters, 60(11), 1301-1303. doi:10.1063/1.107323Fanton, J. T., Opsal, J., Willenborg, D. L., Kelso, S. M., & Rosencwaig, A. (1993). Multiparameter measurements of thin films using beam‐profile reflectometry. Journal of Applied Physics, 73(11), 7035-7040. doi:10.1063/1.352421Leng, J. M., Chen, J., Fanton, J., Senko, M., Ritz, K., & Opsal, J. (1998). Characterization of titanium nitride (TiN) films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry. Thin Solid Films, 313-314, 308-313. doi:10.1016/s0040-6090(97)00838-9Sanza, F. J., Laguna, M. F., Casquel, R., Holgado, M., Barrios, C. A., Ortega, F. J., … Puchades, R. (2011). Cost-effective SU-8 micro-structures by DUV excimer laser lithography for label-free biosensing. Applied Surface Science, 257(12), 5403-5407. doi:10.1016/j.apsusc.2010.10.010Ho, H. P., Law, W. C., Wu, S. Y., Lin, C., & Kong, S. K. (2005). Real-time optical biosensor based on differential phase measurement of surface plasmon resonance. Biosensors and Bioelectronics, 20(10), 2177-2180. doi:10.1016/j.bios.2004.09.01