A newly designed quantitative method allows researchers to enrich and detect low-abundance proteins in serum and plasma without the use of antibodies, which are expensive and difficult to develop (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1204366109). Wei-Jun Qian of Pacific Northwest National Laboratory and coworkers developed an approach they call PRISM, which combines high-pressure, high-resolution separations with intelligent selection and multiplexing strategies for mass spectrometric analysis. They first separate a peptide mixture into 96 fractions using reversed-phase capillary liquid chromatography. They next pick out target fractions using selected reaction monitoring (SRM) mass spectrometry of isotope-labeled synthetic peptide internal standards. The internal standards help them select fractions containing the peptides they’re looking for. Multiple targeted fractions with different elution times are then recombined for conventional LC-SRM analysis. Qian and coworkers were able to quantify proteins in the 50 to 100 pg/mL concentration range without the need for affinity-enrichment reagents. They used the method to quantify prostate-specific antigens in serum samples and in a prostate cancer cell line; their results correlate with those from standard clinical immunoassays.