In our work, we investigated the interactions between a small molecule, folic acid, and biological cells through the interaction of folic acid and folate receptors using a laser scanning confocal imaging-surface plasmon resonance (LSCI-SPR) system. The changes of SPR peaks and cell concentration had good linear relationships, and fluorescence imaging provided further data. The detection limit was as low as 1.0 × 103 cells per mL, and linear coefficients were 0.95206, 0.95454, 0.94287, 0.98711, and 0.99228 for mouse lymphoma (L5178Y TK+/−) cells, mouse lymphoma (EL4) cells, mouse T lymphocytes (Cl.Ly 1+2−/9) cells, human lung cancer (A549) cells, and human oral epidermis carcinoma (KB) cells, respectively. The results indicated that the LSCI-SPR system has potential future application in analyzing small molecule–biological cell affinity and in acquiring quantitative parameters. RSC Advances Issue 70, 2016, Issue in Progress |