Provided herein are instruments and cartridges for processing samples. The cartridges include fluidic circuits in which fluid movement can be regulated by diaphragm valves. In certain cartridges, deformable material providing a diaphragm contacts an interface in the instrument that actuates the diaphragm directly, without intervening actuation layer. Certain cartridges have a plurality of fluidic circuits and fluid distribution channels or pneumatic distribution channels configured to deliver fluids or pneumatic pressure to any of the fluidic circuits, selectively. Certain cartridges have compartments containing on-board reagents. Compartments can be closed by a film attached to a body the cartridge through a heat seal.