A system for processing a sample includes a chamber for receiving a sample, at least one light source, and an imager array configured to generate a sample image of the sample in the chamber. The system can be used to process a sample in a multiplexed manner. For example, one variation of a method for processing a sample includes identifying one or more features of interest in the sample based at least in part on the forms and/or darkness shift of one or more marker particles depicted in the sample image. Another variation of a method includes illuminating the sample with light having a wavelength outside a wavelength detection window of the imager array, to thereby induce at least a portion of the sample to fluoresce light within the wavelength detection window.