Simple contact models are often used in combination with indentation measurements to determine the elastic moduli of materials in the limits of small strain and linear-elastic deformation. However, for soft biological samples these limits can occur at indentation forces comparable to detection noise from the instrument. Here we describe a data analysis method for determining the moduli of soft materials when the measured forces are comparable to the level of instrumental noise; relationships between the force and displacement autocorrelation functions enable the elastic modulus to be determined from indentation curves with large uncertainties in the measured force. In simulations of force-displacement indentation data using the Hertz and Winkler foundation contact models with added noise, we find the autocorrelation analysis enables the accurate measurement of known elastic moduli, even when the noise-to-signal ratio is large throughout an indentation experiment. We also find that this analysis method is more accurate at measuring the modulus at high noise levels compared to directly fitting the model curve to the data. We further validate this approach experimentally by testing a series of polyacrylamide hydrogel slabs prepared within a wide polymer concentration range, finding the measured modulus to be in agreement with the moduli determined through rheological characterization.
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