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A hybrid microfluidic separation device that uses the crossflow and the centrifugation effect to separate human plasma from blood cells has been designed and fabricated. The chip mainly consists of the spiral microchannel, which is divided into inner and outer mcirochannels by micropillar arrays. The slits between the micropillars act as filter. Clogging and jamming in this filtration structure are efficiently alleviated. Remarkably, the width of the inner microchannel is gradually decreasing from inlet to outlet in order to increase separation efficiency. The performances of the separation device were investigated theoretically and experimentally. Due to high separation efficiency and compact structure, it is envisaged that this device can be integrated with other microfluidic device for point-of-care diagnostics in the near future.