A tissue interface module for use with an applicator in a microwave-based tissue modification system, the tissue interface module comprising: an applicator chamber on a proximal side of the tissue interface module, the applicator chamber comprising an opening adapted to receive the applicator; an attachment mechanism positioned in the applicator chamber and adapted to attach the tissue interface module to the applicator; a proximal sealing member positioned at a proximal side of the applicator chamber and adapted to provide a first seal between the tissue interface module and the applicator when the tissue interface module is attached to the applicator; a vacuum interface positioned at a proximal side of the applicator chamber through which a vacuum is applied to the applicator chamber; a tissue acquisition chamber including a tissue acquisition opening on a distal side of the tissue interface module; a central opening between the applicator chamber and the tissue acquisition chamber; an intermediate sealing member surrounding the central opening and adapted to provide a second seal between the tissue interface module and the applicator and to prevent air flow from the tissue acquisition chamber to the applicator chamber when vacuum is applied to the applicator chamber; an airflow pathway within the tissue interface module, the airflow pathway connecting the applicator chamber and the tissue acquisition chamber, the airflow pathway bypassing the intermediate sealing member and the central opening when vacuum is applied to the applicator chamber; and a filter disposed in the airflow pathway, the filter being permeable to air and substantially impermeable to fluids. an applicator chamber on a proximal side of the tissue interface module, the applicator chamber comprising an opening adapted to receive the applicator; an attachment mechanism positioned in the applicator chamber and adapted to attach the tissue interface module to the applicator; a proximal sealing member positioned at a proximal side of the applicator chamber and adapted to provide a first seal between the tissue interface module and the applicator when the tissue interface module is attached to the applicator; a vacuum interface positioned at a proximal side of the applicator chamber through which a vacuum is applied to the applicator chamber; a tissue acquisition chamber including a tissue acquisition opening on a distal side of the tissue interface module; a central opening between the applicator chamber and the tissue acquisition chamber; an intermediate sealing member surrounding the central opening and adapted to provide a second seal between the tissue interface module and the applicator and to prevent air flow from the tissue acquisition chamber to the applicator chamber when vacuum is applied to the applicator chamber; an airflow pathway within the tissue interface module, the airflow pathway connecting the applicator chamber and the tissue acquisition chamber, the airflow pathway bypassing the intermediate sealing member and the central opening when vacuum is applied to the applicator chamber; and a filter disposed in the airflow pathway, the filter being permeable to air and substantially impermeable to fluids.