This invention relates generally to filtration cassettes, and, more particularly to methods of fabricating cross-flow filtration cassettes. Cassettes of the invention are characterized, in part, by a series of sealing channels which selectively seal the filtrate and retentate ports to prevent undesired flow. The sealing channels have formed barriers on either side thereof which create side-walls for precisely controlling the flow of the sealant during the cassette formation. Filtration cassettes of the present invention can be manufactured from conventional membrane and flow screen components and can utilize both injection molding and vacuum assisted resin transfer molding fabrication processes.