Milling with ultraviolet excitation (MUVE) realizes high-throughput multiplex imaging of large three-dimensional samples. The instrumentation may comprise a UV-source attachment, precision stage attachment, and/or a blade assembly, and the instrumentation may overcome several constraints inherent to current state-of-the-art three-dimensional microscopy. MUVE offers throughput that is orders of magnitude faster than other technology by collecting a two-dimensional array of pixels simultaneously. The proposed instrumentation also utilizes serial ablation and provides the opportunity for true whole-organ imaging at microscopic resolution.