A sample vessel retention mechanism for an inverted microscope having an optical objective and a scanning probe microscope (SPM) head. The inverted microscope includes a platform for supporting a sample vessel, in which is formed an aperture sized to provide a passage for the objective of the inverted microscope to approach the sample vessel from below. The retention mechanism provides a vacuum region formed in the platform, with the vacuum region being barometrically coupled with a vacuum generator. Establishment of a vacuum in the vacuum region prevents or substantially reduces oscillation of the sample vessel floor in an operating frequency range of the SPM head.