Construction of stable 3D networks directly on the inner wall of microchannels is of great importance for various microfluidic applications. 3D nest-like networks with large contact surface areas and excellent structural stability arefabricated via a facile, template-free, continuous fluid construction process directly in confined microchannels. Bovine serum albumin (BSA) is chosen as a model albumin to test the adsorption of the network modified microchannel to the target albumin. The high structural stability of the networks is confirmed both by finite element analysis (FEA) simulation and recycling experiments for BSA enrichment. ZnS shells are fabricated based on the original 3D Zn(OH)F networks through in situ chemical conversion. The nest-like networks decorated with Ag nanoparticles (NPs) serve as 3D substrates for surface-enhanced Raman scattering (SERS), exhibiting excellent sensitivity for rapid detection of trace 10(-12) mol L-1 (1 pM) BSA. Three different gap sizes between Ag NPs in the 3D geometry create a large number of SERS hot spots that contribute to the high sensitivity of the networks. Furthermore, a transparent, flexible, microfluidic device containing the 3D nest-like structures exhibits excellent recyclability and flexible stability for trace BSA enrichment, showing potential for application in online SERS detection.