The current invention provides devices, methods and systems involving application of energy and/or a liquefaction promoting medium to a tissue of interest to generate a liquefied sample comprising tissue constituents so as to provide for rapid tissue sampling, tissue decontamination as well as qualitative and/or quantitative detection of analytes that may be part of tissue constituents (e.g., several types of biomolecules, drugs, and microbes). In addition, the current invention provides specific compositions of the said liquefaction promoting medium so as to facilitate liquefaction, preserve liquefied tissue constituents, and enable delivery of molecules into tissues. Determination of tissue composition in the liquefied tissue sample can be used in a variety of applications, including diagnosis or prognosis of local as well as systemic diseases, evaluating bioavailability of therapeutics in different tissues following drug administration, forensic detection of drugs-of-abuse, evaluating changes in the tissue microenvironment following exposure to a harmful agent, and various other applications. The methods, devices and systems are used to deliver one or more drugs through or into the site of the tissue to be liquefied.