A system for processing analytes in samples includes an instrument and a cartridge. The cartridge includes fluid inputs, input and output valve assemblies, processing devices, fluid reservoirs, and channels for carrying samples from the fluid inputs to the fluid reservoirs. The valve assemblies include valves adapted to form a sealed fluid chamber in response to force applied by a movable head assembly of the instrument. Each fluid reservoir is adapted to mate and align with an air displacement pump interface member. A valve assembly includes a recess wall surrounding a recess and a valve assembly wall surrounding both the recess and the recess wall. The recess wall and the valve assembly walls are adapted to mate with and seal against a flexible sheet covering the recess, the recess wall, and the valve assembly wall. The cartridge and instrument include complementary features for finely and coarsely aligning instrument assemblies with portions of the cartridge.