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The concentration of cytokines in blood are often at pictogram per mL and sub-picogram per mL. Recent advances in the sensitivity of immunoassays, such as single molecule arrays (Simoa), have allowed the detection of many of these cytokines that were previously undetectable in blood. While the limits of detection (LOD) of these new technologies are in the femtogram per mL range, the concentrations of cytokines in many healthy individuals can still not be detected. In fact, the quantitative measurement of several important cytokines are< 50% in healthy individuals. We will report on advances to improve the sensitivity of the Simoa technology into the attogram per mL range that improve the quantitative measurement of a broad range of cytokines.