Abstract: Affinity separation compositions and methods are disclosed for separating targets from complex mixtures. Affinity reagents are bound to a solid support oriented in a manner to facilitate the activity of the affinity reagents which are capable of binding specific targets by affinity recognition. Affinity reagents include IgY antibodies, proteins, peptides, nucleotides and polymers. Targets include proteins, protein-protein complexes, protein-nucleotide complexes, nucleotides, cells and subcellular organelles.