Abstract: Detection of immunoglobin G antibodies(IgG) is a very common form of medical diagnostics for viral hepatitis, autoimmune hepatitis and cirrhosis. Development of a reliable and sensitive method for the detection of IgG is hence essential. In this study, myoglobins, serving as a mass tag, were encapsulated in liposomes conjugated with 10-20 monoclonal anti-human IgG for the detection IgG. These bi-functional liposome-anti-IgG complex were subsequently incubated with increasing concentrations of IgG antibodies. The IgG and the mass tag were released by the addition of 25 mM cyano-4-hydroxycinnamic acid to the liposome complex. The results showed that IgG were captured and concentrated in the liposomes, and could be indirectly but reliably quantified by measuring the hemin release from myoglobin via mass analysis. Hemin is a small molecule that can be detected easily without mass discrimination and ion suppression. The amplification effect of this immunoassay can be assessed by measuring the number of hemin released per IgG protein. The use of those bi-functional liposomes was 100 times more sensitive compared to the conventional MALDI-TOF MS analysis. These results demonstrated the potential of myoglobin-encapsulated and antibody receptor-conjugated liposomes in lowering detection limits of both IgG and possibly other antibodies, and increasing the sensitivity of mass analysis for large molecules.