Abstract: The present invention provides a low bed-volume spin column system and methods of use. The system includes various combinations of spin columns with packed beds, a rack for holding the spin columns, a receiver plate that attaches to the rack and that has wells in registration with the spin columns held in the rack, a lid that attaches to the receiver plate and seals the spin columns, and an incubator block configured for accepting the wells of the receiver plate and for incubating the packed bed. The lid, spin columns, rack, receiver plate, and incubator block are preferably capable of being assembled in a nested configuration. In preferred versions of the invention, the rack is compatible with and attachable to conventional 96-well microplates. Further provided are methods of using the spin column system that include quantitatively purifying and analyzing an analyte, removing and preventing air entrainment within the packed bed, and incubating the packed bed while preventing drying thereof.