Abstract: The present disclosure relates in some aspects to methods and compositions for in situ detection of an analyte in a biological sample embedded in a matrix that is attached to metal nanoparticles. In some embodiments, the detection involves generation of a fluorescent signal that is enhanced by the metal nanoparticles. The fluorescent signal can be detected at a 3-dimensional (3D) location in the matrix which corresponds to the 3D location of the analyte in the biological sample.