Quantum resonance fluorescent microscope systems for detecting component substances in a specimen are described. The systems are based on exciting the sample containing the material with a femtosecond to nanosecond probe pulse of collimated light, which is tailored to optimize detection of a given material by separating the probe pulse into component features of frequency, polarization, phase and/or amplitude. The component features are independently shaped and formed into a composite pulse selected to optimize a signature response pulse received from the material. In some cases, two independently re-shaped pulses are combined, where one re-shaped pulse has two mixed polarization states and the other re-shaped pulse is linearly polarized. These two pulses are made to intersect at an angle of 90 degrees so that the combined pulse has electric field in each of the XYZ axes. Selection of the appropriate shapes for the component features of the pulses for a given material is accomplished by testing variations in the features on the material, assigning a fitness value to variants that tend to optimize a distinctive spectral response from the material, and using a genetic algorithm to select the combination of component features that enhances the distinctiveness of the response received over a typical background.