The quantitative analysis of surface antigens on cells, especially red blood cells (RBCs), has attracted increasing attention due to the recognition of antigenic changes that can facilitate early diagnoses. This paper presents an alternative methodology developed using the optical cell-detachment technique to evaluate antibody-antigen interactions and quantitatively analyze the RBC surface antigen expression. RBC subtyping was used to verify the proposed detection principle based on a comparison of the bonding strengths between individual RBCs and antibody coatings. The bonding strengths were measured with serial antibody dilutions with gradually decreasing laser powers, for which a single cell was optically detached from the corresponding antibody-coated surface. With the quantitatively analysis, the proposed alternative methodology was verified as a highly sensitive technique for detecting antigen expression on the RBC surface.