Successful treatment of cancers requires detecting early signs of the disease. One promising way to approach this is to develop minimally invasive tests for the sensitive and specific detection of biomarkers in blood. Irrespective of the detection approach one uses, this remains a challenging task because biomarkers are typically present in low concentrations and there are signals that interfere strongly with prevailing compounds of human fluids. In this paper, we show that elemental encoded particle assay coupled with femtosecond laser-induced breakdown spectroscopy for simultaneous multi-elemental analysis can significantly improve biomarker detectability. An estimated near single molecule per particle efficiency of this method leads to sensitive detection of ovarian cancer biomarker CA125 in human blood plasma. This work opens new ways for earlier detection of cancers and for multiplex assay developments in various analytical applications from proteomics, genomics, and neurology fields.