We describe a novel sandwich assay based on surface enhanced Raman scattering (SERS) comprised of buoyant silica microspheres coated with antibodies against the β subunit of the cholera toxin (CT), and gold nanoparticles tagged with a Raman reporter, shelled with silica and coated with antibodies against the β subunit of the CT. Together these components couple to form a sandwich which, after incubation, floats on the surface of the sample. The buoyant silica microparticle/nanoparticle reporter combination has been coined a lab on a bubble (LoB). LoB materials may provide a platform for rapid detection of antigen in solution and offers advantages over lateral flow or magnetic pull-down assays. The Raman reporter provides a unique and intense signal to indicate a positive analysis. Our limit of detection for the β subunit of the CT in a buffer based system is 1100 ng.