Many researchers do not want blocked beads because the blocking protein can and does leach some. Not much but some. It is not covalently linked, so some leaching occurs. Some researchers do not want any protein leaching since this would interfere, for example, with protein sequencing and the specificity of the beads in their particular application. Other researchers require low nonspecific binding with very high binding capacity and don’t care about leaching. These researchers do want a blocked bead. If one is going to capture biotinylated DNA, you probably don’t need blocked beads. pH and detergents turn out to be more important factors for reducing DNA-based NSB than any other factors. If one is going to capture biotinylated antibody or proteins, one should block the beads for optimal results and minimal NSB. For some applications, pre-blocked beads would be a good thing, and for others, not needed. Regarding reduction of binding capacity using blocked beads…experiments we have done indicate that binding capacity is reduced for antibodies. But the reason for this is because 15% of the binding is NSB to begin with, and not related to biotin/streptavidin interactions. Even after extensive casein blocking, our NanoLink™ Streptavidin beads still bind 250 µg of biotinylated IgG vs. 80 µg for Invitrogen’s product (based on their website) per mg. So after blocking, we still bind 3X more antibody than anybody else. Without blocking, we capture a great deal more biotinylated IgG, but this increased capture is nonspecific binding. I believe that we have captured up to 400 µg of biotinylated IgG per mg of NanoLink™ without blocking the beads first. So yes, you will see a reduction in binding of biotinylated proteins, but this reduction is not due to loss of streptavidin, but rather blocking of NSB binding sites.