Since molecular cluster ion beams are expected to have various chemical effects, they are promising candidates for improving the secondary ion yield of Tof-SIMS. However, in order to clarify the effect and its mechanism, it is necessary to generate molecular cluster ion beams with various chemical properties and systematically examine it. In this study, we have established a method to stably form various molecular cluster ion beams from relatively small amounts of liquid materials for a long time by the bubbling method. Furthermore, we applied the cluster ion beams of water, methanol, methane, and benzene to the primary beam of SIMS and compared the molecular ion yields of aspartic acid. The effect of enhancing the yields of [M+H]+ ion of aspartic acid was found to be the largest for the water cluster and small for the methane and benzene clusters. These results indicate that the chemical effect contributes to the desorption/ionization process of organic molecules by the molecular cluster ion beam.