Methods for enumeration of rare cells

A method of detecting a rare circulating cell in a blood sample, present at a concentration of less than 1 in 105 in the population, the method comprising:

• contacting the sample with an effective amount of a labeling nanoparticle, wherein the labeling nanoparticle comprises a virus-like particle (VLP) directly conjugated by covalent bonds to (i) a plurality of light emitting moieties;
• and (ii) a plurality of specific binding moieties that selectively bind to the circulating cell;
• washing the sample free of unbound labeling nanoparticle wherein the sample is immobilized on a membrane prior to contacting the labeling nanoparticle or following contacting with the labeling nanoparticle;
• contacting the washed sample with a substrate for the light emitting moiety;
• and
• quantitating the emission of light, wherein the presence of light is indicative of the presence of the circulating cell, wherein the method is performed in the absence of affinity based enrichment of cells.