An optical system includes a sample substrate having a surface, the surface defining a 2-dimensional sample plane. The system includes an excitation source configured to provide excitation light to the sample substrate. The system further includes an optical detector configured to receive emission light from the sample substrate and generate detection data. The system also includes a scan head configured at least (i) to direct the excitation light towards the sample substrate, (ii) to receive emission light from the sample substrate and direct the emission light towards the optical detector, and (iii) for scanning relative to the sample substrate. The system includes at least one actuator configured to scan the scan head relative to the sample substrate, the at least one actuator being configured to provide at least one of (1) a relative linear motion and a relative angular motion about a rotational axis generally perpendicular to the sample plane and (2) two relative angular motions about two respectively different rotational axes generally perpendicular to the sample plane.