A fluid-handling cassette assembly comprising: A middle cassette interposed between a first outer cassette and a second outer cassette; each said cassette (228, 230, 232) comprising: a mid-plate (134; 242, 244) positioned between a first plate and a second plate, said plates having a length, a width and a plate thickness, a first side of the mid-plate (134; 242, 244) opposing the first plate and a second side of the mid-pate opposing the second plate; the first plate spaced apart from the mid-plate (134; 242, 244) defining a width of a first inter-plate space, and the second plate spaced apart from the mid-plate (134; 242, 244) defining a width of a second inter-plate space; an edge of the cassette having a cassette thickness defined by the thickness of each plate plus the width of the first and second inter-plate spaces (136, 138), and a face of the cassette being defined by the length and width of the first or second plate (136, 138); a plurality of diaphragm valves or pumps comprising valve or pump actuation chambers connected to actuation channels running parallel to the face of the cassette (228, 230, 232) within the first or second inter-plate space (136, 138), and terminating in respective cassette valve or pump actuation ports at a first edge of the cassette (228, 230, 232) between the first or second inter-plate space (136, 138); and a fluid-handling pod (234, 236) positioned in an inter-cassette space between the middle cassette and the first or second cassette (228, 232); said pod (234, 236) having a fluid connection to fluid channels in the middle, first or second cassette (228, 230, 232) via a fluid conduit penetrating the face of the middle, first or second cassette (228, 230, 232); wherein the first edge of the middle, first and second cassettes (228, 230, 232) are located on a first side of the cassette assembly, so that the cassette valve or pump actuation ports are configured to plug into or unplug from an actuation port receptacle assembly opposite the first side of the cassette assembly. A middle cassette interposed between a first outer cassette and a second outer cassette; each said cassette (228, 230, 232) comprising: a mid-plate (134; 242, 244) positioned between a first plate and a second plate, said plates having a length, a width and a plate thickness, a first side of the mid-plate (134; 242, 244) opposing the first plate and a second side of the mid-pate opposing the second plate; the first plate spaced apart from the mid-plate (134; 242, 244) defining a width of a first inter-plate space, and the second plate spaced apart from the mid-plate (134; 242, 244) defining a width of a second inter-plate space; an edge of the cassette having a cassette thickness defined by the thickness of each plate plus the width of the first and second inter-plate spaces (136, 138), and a face of the cassette being defined by the length and width of the first or second plate (136, 138); a plurality of diaphragm valves or pumps comprising valve or pump actuation chambers connected to actuation channels running parallel to the face of the cassette (228, 230, 232) within the first or second inter-plate space (136, 138), and terminating in respective cassette valve or pump actuation ports at a first edge of the cassette (228, 230, 232) between the first or second inter-plate space (136, 138); and a mid-plate (134; 242, 244) positioned between a first plate and a second plate, said plates having a length, a width and a plate thickness, a first side of the mid-plate (134; 242, 244) opposing the first plate and a second side of the mid-pate opposing the second plate; the first plate spaced apart from the mid-plate (134; 242, 244) defining a width of a first inter-plate space, and the second plate spaced apart from the mid-plate (134; 242, 244) defining a width of a second inter-plate space; an edge of the cassette having a cassette thickness defined by the thickness of each plate plus the width of the first and second inter-plate spaces (136, 138), and a face of the cassette being defined by the length and width of the first or second plate (136, 138); a plurality of diaphragm valves or pumps comprising valve or pump actuation chambers connected to actuation channels running parallel to the face of the cassette (228, 230, 232) within the first or second inter-plate space (136, 138), and terminating in respective cassette valve or pump actuation ports at a first edge of the cassette (228, 230, 232) between the first or second inter-plate space (136, 138); and a fluid-handling pod (234, 236) positioned in an inter-cassette space between the middle cassette and the first or second cassette (228, 232); said pod (234, 236) having a fluid connection to fluid channels in the middle, first or second cassette (228, 230, 232) via a fluid conduit penetrating the face of the middle, first or second cassette (228, 230, 232); wherein the first edge of the middle, first and second cassettes (228, 230, 232) are located on a first side of the cassette assembly, so that the cassette valve or pump actuation ports are configured to plug into or unplug from an actuation port receptacle assembly opposite the first side of the cassette assembly.