A pneumatic controlled nanosieve device is demonstrated for the efficient capture and release of 15 nm quantum dots. This device consists of a 200 nm deep glass channel and a polydimethylsiloxane-based pneumatic pressure layer to enhance target capture. The fluid motion inside the nanosieve is studied by computational fluidic dynamics (CFD) and microfluidic experiments, enabling efficient target capture with a flow rate as high as 100 μl/min. In addition, microgrooves are fabricated inside the nanosieve to create low flow rate regions, which further improves the target capture efficiency. A velocity contour plot is constructed with CFD, revealing that the flow rate is the lowest at the top and bottom of the microgrooves. This phenomenon is supported by the observed nanoparticle clusters surrounding the microgrooves. By changing the morphology and pneumatic pressure, this device will also facilitate rapid capture and release of various biomolecules.