Described are devices, methods and systems for applying energy and/or a liquefaction promoting medium to a tissue of interest to generate a liquefied tissue sample. The liquefied tissue sample may be removed from the tissue of interest. Also described are compositions of the liquefaction promoting medium that may facilitate liquefaction, preserve liquefied tissue constituents, and/or enable delivery of molecules into tissues. The sample may include tissue constituents to provide for rapid tissue sampling, tissue decontamination as well as detection of analytes. One or more drugs may be delivered through or into the tissue of interest. Determination of tissue composition in the liquefied tissue sample can be used, e.g., for diagnosis or prognosis of diseases, evaluating bioavailability of therapeutic agents in different tissues following administration, forensic detection of drugs-of-abuse, evaluating changes in the tissue microenvironment following exposure to a harmful agent, and the like.