Abstract: An optical system for non-invasive cytometry of mammalian cells includes a light source, a cell positioner, an optical imager, an optical wavefront sensor and a computer. The light source produces an illuminating beam of spatially coherent radiation. The cell positioner sequentially moves a single cell from a population of multiple cells into a sub-aperture region of the illumination beam whose wavefront is perturbed in response to the physical structure of the single cell. An optical system relays a magnified image of the sub-aperture region containing the cell to an image plane. At the image plane a Shack-Hartmann wavefront sensor is positioned. Within the pupil of the wavefront sensor the local tilts of the wavefront in the sub-aperture region are measured and sent to a computer. Software calculates the Zernike coefficients corresponding to the aberration induced by the structure of each cell. Their Zernike signatures classify the cells into distinct types.