Multi-layer 3-D microfluidic circuits are the driving platform for micro-total analysis systems in the current era. The traditional fabrication for these fluidic circuits is planar. For building multi-layer structures a precise alignment for multiple layers is required, which makes the fabrication very difficult. We have invented a flow-based extrusion process for multi-layer microfluidic circuits in polymer substrates. The channels can be as small as 100nm with multi-materials embedded in the substrate. Such a direct-write 3-D process will enhance testing and prototyping of microfluidic circuits and enable fabrication of true 3-D structures.