A noninvasive method for estimating a concentration of a target analyte in a sample comprises generating a first and second (reference) radiation, a principal radiation and a target analyte carrier detection radiation; directing the first, second, principal and the target analyte carrier detection radiations at the sample which includes the target analyte; and detecting a first, second, principal and target analyte carrier detection amount of the radiation that leaves the sample. The method further comprises modulating the sample thickness in order to achieve time-wise or spatial target analyte concentration variation within the sample. The method further comprises generating first, second, principal and target analyte carrier detection measurement data based respectively on the first, second, the principal and the target analyte carrier detected amounts of radiation; numerically processing the first, second, principal and target analyte carrier detection measurement data to obtain a weighted combination of the first measurement data and the second measurement data that balances the principal measurement data with respect to a sample background; and estimating the concentration of the target analyte based on the difference between the balanced weighted combination of the first measurement data and the second measurement data vs. the principal measurement data.