Schematic representation of particle structure and function. A. Particles are constituted by a bait containing core, surrounded by a sieving shell. Candidate biomarkers can be associated with high abundance carriers such as albumin. B. When introduced into a complex solution, such as serum, core-shell particles affinity capture all molecular species below the molecular weight cut off of the shell, strip the target biomarkers away from the excluded carrier protein by affinity competition, and preserve the captured molecules from degradation.