MEMS squeezer for the measurement of single cell rupture force, stiffness change, and hysteresis

Abstract

A MEMS squeezer able to compress single living cells underwater until rupture was designed and tested. The relatively large motion range of the device in aqueous media (~2.5 µm) allows provoking cell disruption while measuring cell mechanical properties before and after membrane rupture. An AC driven electrothermal micro actuator with mechanical amplification pressed single cells against a reference back spring. Deformations of the cell and the reference spring were measured with nanoscale resolution using optical Fourier transform techniques. The motion of the reference spring divided by the cell deformation provides the cell stiffness relative to the reference spring constant. An abrupt change in the cell stiffness and the appearance of cracks indicated the cell wall rupture force was reached. A total of 22 baker’s yeast cells (Saccharomyces cerevisiae) were squeezed with the micro device. The average force necessary to rupture the cell membrane was 0.47 ± 0.1 µN. Before rupture the cells had an average stiffness of 9.3 ± 3.1 N m−1; the post-rupture stiffness dropped to 0.94 ± 0.57 N m−1. Cell hysteresis was also measured: cells squeezed and released before reaching the rupture force showed residual deformations below 100 nm, while cells squeezed past the rupture force and then released showed residual deformations between 490 and 990 nm.