An improved method for non-invasively measuring a concentration of a target analyte dissolved in a fluid flowing through a sample is presented. It includes directing a probe beam of electromagnetic radiation, having time multiplexed components of different wavelengths, where at least one of the time-multiplexed components consists of two different simultaneous wavelengths through the sample and measuring the difference of the absorption of the radiation of the time-multiplexed components at different sample states. During sample state changes, the amount of fluid containing the target analyte within the sample is changing, varying the total amount of target analyte in the sample, and the absorption properties of the sample. The sample states may be produced by compressing and uncompressing the tissue sample. The method is useful in measuring the concentration of a target analyte, such as glucose, in tissue containing blood.