The disclosed methods and apparatus concern Raman spectroscopy using metal coated nanocrystalline porous silicon substrates. Porous silicon substrates may be formed by anodic etching in dilute hydrofluoric acid. A thin coating of a Raman active metal, such as gold or silver, may be coated onto the porous silicon by cathodic electromigration or any known technique. In certain alternatives, the metal coated porous silicon substrate comprises a plasma-oxidized, dip and decomposed porous silicon substrate. The metal-coated substrate provides an extensive, metal rich environment for SERS, SERRS, hyper-Raman and/or CARS Raman spectroscopy. In certain alternatives, metal nanoparticles may be added to the metal-coated substrate to further enhance the Raman signals. Raman spectroscopy may be used to detect, identify and/or quantify a wide variety of analytes, using the disclosed methods and apparatus. In some disclosed methods, Raman spectroscopy may be used to detect nucleotides, purines or pyrimidines at the single molecule level.
RELATED APPLICATIONS
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation application of U.S. application Ser. No. 10/680,583 filed Oct. 7, 2003, now U.S. Pat. No. 6,989,897; which is a continuation-in-part application of U.S. application Ser. No. 10/368,976 filed Feb. 18, 2003, now pending; which is a continuation-in-part application of U.S. application Ser. No. 10/171,357 filed Jun. 12, 2002, now U.S. Pat. No. 6,970,239. The disclosure of each of the prior applications is considered part of and is incorporated by reference in the disclosure of this application.
Surface-enhanced Raman spectroscopic (SERS) systems and methods for detecting biomolecules of interest, such as a virus, bacterium, or other infectious agent, are provided. A spectroscopic assay based on surface enhanced Raman scattering (SERS) using a silver nanorod array substrate fabricated by oblique angle deposition has been developed that allows for rapid detection of trace levels of viruses or bacteria with a high degree of sensitivity and specificity. This novel and improved SERS assay can detect minor spectral differences within strains of a single virus type such as respiratory syncytial virus or influenza virus in the presence of biological media. The method provides rapid diagnostics for direct molecular and structural characterization of virus strains and virus gene deletion mutants generating reproducible viral spectra without viral manipulation.
