Beyond the paradigm of nanomechanical measurements on cells using AFM: An automated methodology to rapidly analyse thousands of cells.
Nanomechanical properties of cells could be considered as cellular biomarkers. The main method used to access the mechanical properties is based on nanoindentations measurements, performed with an operator manipulated Atomic Force Microscope (AFM) which is time-consuming, and expensive. This is one of the reasons preventing the transfer of AFM technology into clinical laboratories. In this paper we report a methodology which includes an algorithm (transferred to a script, executed on a commercial AFM) able to automatically move the tip onto a single cell and through several cells to record force curves combined with a smart strategy of cell immobilization. Cells are placed into microwells of a microstructured polydimethylsiloxane (PDMS) stamp. Inside a classical 100x100 µm2 AFM field, 80 to 100 cells are immobilized. In an optimal configuration we were able to measure a population of 900 Candida albicans cells both unmodified and caspofungin treated in 4 h, which represents an unprecedented performance.