A tissue penetrating system includes a plurality of cartridges, each with a distal port and a proximal port. A plurality of penetrating members are provided, each being coupled to a cartridge. Each penetrating member has a sharpened distal tip and a shaft portion slidably disposed within the cartridge. A seal is formed by a fracturable material between the penetrating member and the cartridge. The seal is positioned at one or both of a distal port or a proximal port of the cartridge. A user interface is configured to relay at least one of, skin penetrating performance or a skin penetrating setting.