A body fluid sampling system for use on a tissue site has a housing and a penetrating member driver at least partially within the housing. At least one cartridge is in the housing. The cartridge includes an analyte sensor in a sample chamber configured to receive body fluid from a wound in tissue created by a penetrating member. A penetrating member is associated with the sample chamber. Each penetrating member, and its associated sample chamber, has a combined occupied volume of no more than about 5.0 cm3. The penetrating member is at least partially co-located with the analyte sensor in the sample chamber. The sample chamber receives body fluid from a wound in tissue created by a penetrating member, and the analyte sensor determines analyte levels using a body fluid sample of less than about 1 microliter. A transport mechanism engages the cartridge. The penetrating member is operatively engaged with the penetrating member driver when moved into position by the transport mechanism. The driver provides the force to advance the penetrating member. A user interface on the housing displays information to a user.