A blood filtration device, system, and method that can and selectively remove or reduce an unwanted, in certain cases unknown, substance from a patients blood stream. More specifically, a specific size or size range of unwanted substance is selectively removed. The unwanted substance includes one or more of a pathogen, a toxin, an activated cell, and an administered drug. The device and system employ a microfluidic separation device that minimizes thrombogenesis and can permit the use of anticoagulants to be avoided. The device or system can be portable and can include its own power supply. Sensors in the system may monitor for the presence and/or concentration of unwanted species including pathogens or drugs and invoke a blood cleansing process responsively to the sensor signals in closed loop control process. The control may combine the infusion of therapeutic agents into the blood of a patient as well.
