Abstract: Systems comprising a diffraction grating, a light source configured to illuminate at a limited waveband, an optical detection system configured to detect zero and non-zero diffraction orders of light, and a signal processing unit adapted to analyze zero and non-zero diffraction orders to determine time-dependent changes in effective optical depth are provided. Methods for use of these systems for real-time detection of cell replication, microorganism detection, and for selecting a therapeutic agent for treating a microorganism are also provided.