In one aspect, the present invention generally provides methods for fabricating substrates for use in a variety of analytical and/or diagnostic applications. Such a substrate can be generated by exposing a semiconductor surface (e.g., silicon surface) to a plurality of short laser pulses to generate micron-sized, and preferably submicron-sized, structures on the surface. The structured surface can then be coated with a thin metallic layer, e.g., one having a thickness in a range of about 10 nm to about 1000 nm.