Tomáš Vičar, Michal Masarik, Ivo Provaznik, Vratislav Cmiel, Larisa Chmelikova, Radim Kolar, Jiri Chmelik and Jaromir Gumelec presented an approach for viscoelasticity measurement using QPI and shear stress induction by fluid flow. The article got published on Biophysical Journal. It allows to eliminate the influence of the fluidic system and reliably measure both the shear modulus and viscosity of the cells in high throughput. The described method enables also the simultaneous determination of cell refractive index map, cell dry mass map, and morphology (multimodal cellular characterization in a single measurement). One of the main advantages of using our holographic phase microscope Q-Phase, is the possibility to study multiple cell modalities at a same time.
Cell viscoelastic properties are affected by the cell cycle, differentiation, and pathological processes such as malignant transformation. Therefore, evaluation of the mechanical properties of the cells proved to be an approach to obtaining information on the functional state of the cells. Most of the currently used methods for cell mechanophenotyping are limited by low robustness or the need for highly expert operation. In this paper, the system and method for viscoelasticity measurement using shear stress induction by fluid flow is described and tested. Quantitative phase imaging (QPI) is used for image acquisition because this technique enables one to quantify optical path length delays introduced by the sample, thus providing a label-free objective measure of morphology and dynamics. Viscosity and elasticity determination were refined using a new approach based on the linear system model and parametric deconvolution. The proposed method allows high-throughput measurements during live-cell experiments and even through a time lapse, whereby we demonstrated the possibility of simultaneous extraction of shear modulus, viscosity, cell morphology, and QPI-derived cell parameters such as circularity or cell mass. Additionally, the proposed method provides a simple approach to measure cell refractive index with the same setup, which is required for reliable cell height measurement with QPI, an essential parameter for viscoelasticity calculation. Reliability of the proposed viscoelasticity measurement system was tested in several experiments including cell types of different Young/shear modulus and treatment with cytochalasin D or docetaxel, and an agreement with atomic force microscopy was observed. The applicability of the proposed approach was also confirmed by a time-lapse experiment with cytochalasin D washout, whereby an increase of stiffness corresponded to actin repolymerization in time.
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