A system comprising a host instrument and a microfluidic cartridge for assay of a target analyte or analytes in a biological sample, said cartridge comprising: a) a plastic, thermally insulative cartridge body enclosing: i) a hydraulic works comprising a sample inlet (104; 801), one or more on-board liquid or dry reagents for an assay, and a wettable downstream microfluidic subcircuit with channels and chambers fluidly connected to said upstream inlet (104; 801) and vented at a downstream vent; and ii) a pneumatic works comprising an inlet or inlets for receiving pneumatic pressure and a pneumatic subcircuit with channels and chambers configured for conveying said pneumatic pressure therefrom; and b) at least one pneumohydraulic diaphragm configured for interfacing a hydraulic chamber of said wettable microfluidic subcircuit with a pneumatic chamber of said pneumatic subcircuit, said pneumohydraulic diaphragm having a first side facing said hydraulic chamber and a second side facing said pneumatic chamber; wherein said pneumohydraulic diaphragm is selected from: A) an elastic, energy-storing pneumohydraulic diaphragm configured for passively storing a liquid volume under a hydraulic pressure and releasing said liquid volume during wetout of a downstream channel or chamber of said wettable microfluidic subcircuit; B) a duplexedly layered pneumohydraulic diaphragm (602, 603) having a liquid center configured for storing and releasing a liquid reagent; C) a pneumohydraulic diaphragm capable of distending and eliminating headspace from a hydraulic chamber during wetout; or D) a pair of pneumohydraulic diaphragms comprising a first pneumohydraulic diaphragm interfacing a first hydraulic chamber with valved inlet and a second pneumohydraulic diaphragm interfacing a second hydraulic chamber with valved outlet, and an elevated intercommunicating channel between said first and second hydraulic chambers, wherein said pair is configured for reciprocally exchanging fluid through said channel by applying opposing pressure differentials across said first and second pneumohydraulic diaphragms (1011, 1021); and wherein said hydraulic chambers and diaphragms are configured for preventing or reducing bubble entrainment or reagent washout during wetout, fill, pumping or rehydration steps of an assay, and characterized in that said hydraulic works is configured for operation when mounted on a tilted stage of the host instrument at a tilt angle theta of 10-35 degrees relative to the ground plane and at least one hydraulic chamber is configured with an outlet and intercommunicating channel positioned superiorly relative to said chamber for venting a gas or discharging a bubble from said chamber. a) a plastic, thermally insulative cartridge body enclosing: i) a hydraulic works comprising a sample inlet (104; 801), one or more on-board liquid or dry reagents for an assay, and a wettable downstream microfluidic subcircuit with channels and chambers fluidly connected to said upstream inlet (104; 801) and vented at a downstream vent; and ii) a pneumatic works comprising an inlet or inlets for receiving pneumatic pressure and a pneumatic subcircuit with channels and chambers configured for conveying said pneumatic pressure therefrom; and i) a hydraulic works comprising a sample inlet (104; 801), one or more on-board liquid or dry reagents for an assay, and a wettable downstream microfluidic subcircuit with channels and chambers fluidly connected to said upstream inlet (104; 801) and vented at a downstream vent; and ii) a pneumatic works comprising an inlet or inlets for receiving pneumatic pressure and a pneumatic subcircuit with channels and chambers configured for conveying said pneumatic pressure therefrom; and b) at least one pneumohydraulic diaphragm configured for interfacing a hydraulic chamber of said wettable microfluidic subcircuit with a pneumatic chamber of said pneumatic subcircuit, said pneumohydraulic diaphragm having a first side facing said hydraulic chamber and a second side facing said pneumatic chamber; A) an elastic, energy-storing pneumohydraulic diaphragm configured for passively storing a liquid volume under a hydraulic pressure and releasing said liquid volume during wetout of a downstream channel or chamber of said wettable microfluidic subcircuit; B) a duplexedly layered pneumohydraulic diaphragm (602, 603) having a liquid center configured for storing and releasing a liquid reagent; C) a pneumohydraulic diaphragm capable of distending and eliminating headspace from a hydraulic chamber during wetout; or D) a pair of pneumohydraulic diaphragms comprising a first pneumohydraulic diaphragm interfacing a first hydraulic chamber with valved inlet and a second pneumohydraulic diaphragm interfacing a second hydraulic chamber with valved outlet, and an elevated intercommunicating channel between said first and second hydraulic chambers, wherein said pair is configured for reciprocally exchanging fluid through said channel by applying opposing pressure differentials across said first and second pneumohydraulic diaphragms (1011, 1021); and wherein said hydraulic chambers and diaphragms are configured for preventing or reducing bubble entrainment or reagent washout during wetout, fill, pumping or rehydration steps of an assay, and characterized in that said hydraulic works is configured for operation when mounted on a tilted stage of the host instrument at a tilt angle theta of 10-35 degrees relative to the ground plane and at least one hydraulic chamber is configured with an outlet and intercommunicating channel positioned superiorly relative to said chamber for venting a gas or discharging a bubble from said chamber.