Some embodiments presented in this disclosure concern an Automated Tissue Dissection (ATD) System. An ATD system is a one stop, and potentially low-cost, system to perform dissections on a substrate from pathologist digital mark or pen mark on the substrate using non-contact and/or mechanical method to extract a Formalin-Fixed Paraffin-Embedded (FFPE) tissue sample with: (a) only the ROI or ROIs as area to be saved; and (b) remove or decompose nucleic acid content in the region of no interest (RONI) and collect all tissue sample from a standard microscope substrate into a specific container.