Modeling Ramp-hold Indentation Measurements based on Kelvin-Voigt Fractional Derivative Model.

Interpretation of experimental data from micro- and nano-scale indentation testing is highly dependent on the constitutive model selected to relate measurements to mechanical properties. The Kelvin-Voigt Fractional Derivative model (KVFD) offers a compact set of viscoelastic features appropriate for characterizing soft biological materials. This paper provides a set of KVFD solutions for converting indentation testing data acquired for different geometries and scales into viscoelastic properties of soft materials. These solutions, which are mostly in closed-form, apply to ramp-hold relaxation, load-unload and ramp-load creep-testing protocols. We report on applications of these model solutions to macro- and nano-indentation testing of hydrogels, gastric cancer cells and ex vivo breast tissue samples using an Atomic Force Microscope (AFM). We also applied KVFD models to clinical ultrasonic breast data using a compression plate as required for elasticity imaging. Together the results show that KVFD models fit a broad range of experimental data with a correlation coefficient typically R2 > 0.99. For hydrogel samples, estimation of KVFD model parameters from test data using spherical indentation versus plate compression as well as ramp relaxation versus load-unload compression all agree within one standard deviation. Results from measurements made using macro- and nano-scale indentation agree in trend. For gastric cell and ex vivo breast tissue measurements, KVFD moduli are, respectively, 1/3 - 1/2 and 1/6 of the elasticity modulus found from the Sneddon model. In vivo breast tissue measurements yield model parameters consistent with literature results. The consistency of results found for a broad range of experimental parameters suggest the KVFD model is a reliable tool for exploring intrinsic features of the cell/tissue microenvironments.