Serum tumor marker detection on PEGylated lipid membrane using biosensor based on total internal reflection imaging ellipsometry

We describe highly sensitive, label-free, real time detection of the biomarker CA19-9 using microarray biosensors based on total internal reflection imaging ellipsometry (TIRIE), in which anti-CA19-9 is immobilized onto the PEGylated phospholipid membrane. Strong resistance against non-specific adsorption of PEGylated lipid membrane allows direct serum assay without the blocking agent. We find that PEG density has an influence on antibody assembly and only a proper amount of PEG is appropriate for antigen binding. Two different methods for antibody assembly are compared and finally protein A is preferred due to its higher protein binding efficiency. The estimated detection limit of CA19-9 is 18.2 U/ml, which is lower than the cut-off value for normal level (37 U/ml). Regression analysis between the results of microarray biosensor and electrochemiluminescence immunoassay (ECLIA) suggests a high correlation (R = 0.989). The capability for real-time monitoring of tumor marker with high sensitivity and selectivity in clinically relevant samples opens up substantial possibilities for early cancer diagnosis and treatment.