Microfluidic microsystems are often designed to analyze samples of small volumes of fluids; however, some applications require the analysis of larger volumes. The ideal miniaturized microfluidic analytical device should be autonomous and capable of integrating all the required functions within a single fluidic network. While a number of self-powered microfluidic network designs are available, the autonomous manipulation of large sample volumes in microsystems is still a challenge. We have developed a universal self-powered microfluidic architecture by combining polymeric micropumps and plastic microfluidic cartridges, which may be adapted to a large range of volumes of fluids. Our polymeric micropumps were able to trigger flow rates from 0.25 to 20 μL min–1 during more than 90 min, moving over 800 μL of the fluid. A number of fluidic operations were demonstrated, including mixing, aliquoting, waste storage, and autodraining of the microfluidic channels. Finally, a self-powered cartridge for the separation of plasma from whole blood was successfully validated, demonstrating that this constitutes a universal scheme to process a wide range of fluid volumes, which is an unprecedented fact in self-powered microfluidics.