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The effect of finite sample thickness in scanning ion conductance microscopy stiffness measurements

Investigating the mechanical properties of soft biological samples on the single-cell level is of great interest as cell mechanics play a central role in many physiological processes in health and disease. Scanning ion conductance microscopy (SICM) is an emerging technique for measuring cell stiffness on the micro- and nanometer scale in a non-contact fashion. However, as SICM stiffness measurements are based on a localized deformation of the sample, they are affected by the thickness of the sample. We found experimentally and numerically that the apparent stiffness of a thin sample is overestimated. We present a straightforward correction method to account for this effect and derive a thickness-dependent, multiplicative correction factor, which we apply to SICM stiffness mapping of living cells. The correction method allows us to quantitatively measure the stiffness of thin samples with SICM and is, therefore, essential for the comprehensive application of SICM to nanomechanical measurements.