A method of detecting one or more different populations of target rare molecules which are indicative of particular populations of cells in a sample suspected of containing the one or more different populations of rare molecules and non-rare molecules, the method comprising: (a) enhancing the concentration of the one or more different populations of target rare molecules over that of the non-rare molecules to form a concentrated sample through filtration of cellular target rare molecules, or binding non-cellular target rare molecules to one or more capture particle entities and filtration, (b) incubating the concentrated sample with, for each different population of target rare molecules, an affinity agent that comprises a specific binding partner that is specific for and binds to a target rare molecule of one of the populations of the target rare molecules wherein the affinity agent comprises a mass spectrometry label precursor which includes 10 to 100,000 mass spectrometry labels, each mass spectrometry label having a unique mass of 1 Da to 3 kDa and being detectable by primary mass, wherein said mass should not be present in the sample to be analyzed, and wherein the affinity agent may be non-particulate or particulate, (c) forming a retentate and a filtrate by contacting the incubated sample with a porous matrix, (d) subjecting one or both of the retentate and the filtrate to an alteration agent that facilitates the formation of a mass spectrometry label from the mass spectrometry label precursor from the affinity agent, (e) subjecting one or both of the retentate and the filtrate to mass spectrometry analysis to determine the presence and/or amount of each different mass spectrometry label, and (f) relating the presence and/or amount of each different mass spectrometry label to the present and/or amount of each different population of target rare molecules in the sample. (a) enhancing the concentration of the one or more different populations of target rare molecules over that of the non-rare molecules to form a concentrated sample through filtration of cellular target rare molecules, or binding non-cellular target rare molecules to one or more capture particle entities and filtration, (b) incubating the concentrated sample with, for each different population of target rare molecules, an affinity agent that comprises a specific binding partner that is specific for and binds to a target rare molecule of one of the populations of the target rare molecules wherein the affinity agent comprises a mass spectrometry label precursor which includes 10 to 100,000 mass spectrometry labels, each mass spectrometry label having a unique mass of 1 Da to 3 kDa and being detectable by primary mass, wherein said mass should not be present in the sample to be analyzed, and wherein the affinity agent may be non-particulate or particulate, (c) forming a retentate and a filtrate by contacting the incubated sample with a porous matrix, (d) subjecting one or both of the retentate and the filtrate to an alteration agent that facilitates the formation of a mass spectrometry label from the mass spectrometry label precursor from the affinity agent, (e) subjecting one or both of the retentate and the filtrate to mass spectrometry analysis to determine the presence and/or amount of each different mass spectrometry label, and (f) relating the presence and/or amount of each different mass spectrometry label to the present and/or amount of each different population of target rare molecules in the sample.