A photonic crystal substrate exhibiting resonant enhancement of multiple fluorophores has been demonstrated. The device, which can be fabricated uniformly from plastic materials over a ˜3×5 in2 surface area by nanoreplica molding, features a 1-D periodic grating structure which utilizes two distinct resonant modes to enhance electric field stimulation of a first dye excited by a first laser (e.g., λ=632.8 nm laser exciting cyanine-5) and a second dye excited by a second laser (e.g., λ=532 nm laser exciting cyanine-3). The first and second lasers could be replaced by a single variable wavelength (tunable) laser. Resonant coupling of the laser excitation to the photonic crystal surface is obtained for each wavelength at a distinct incident angle θ. The photonic crystal is capable of amplifying the output of any fluorescent dye with an excitation wavelength in a given wavelength range (e.g., the range 532 nm