Abstract: A microfluidic device and method for enzymatic processing of ultra-long macromolecules is accomplished using a microfluidic device a reaction chamber with a first manifold, a second manifold, and a plurality of reaction channels. Each reaction channel extends from the first manifold to the second manifold. First inlet and outlet channels fill the reaction channels via the manifolds with one or more macromolecule containers suspended in a first carrier fluid. The first inlet and outlet channels are configured such that a flow is guided through the reaction channels, and an enzymatic reagent is fed to the reaction chamber essentially without displacing the macromolecule containers trapped in the reaction channels. The second set of inlets and outlets are configured such that a flow established from the second inlet to the second outlet is guided through at least one of the manifolds and bypasses the reaction channels.