An improved method for non-invasively measuring a concentration of a targetanalyte dissolved in a fluid flowing through a sample is presented. It includesdirecting a probe beam of electromagnetic radiation, consisting of time multiplexedcomponents of different wavelengths, where at least one of the time-multiplexedcomponents consists of two different simultaneous wavelengths, whose intensityrelation defines the effective wavelength of their combination, through thesample and measuring the difference of the absorption of the radiation of thetime- multiplexed components at different sample states. During sample statechanges, the amount of fluid containing the target analyte within the sampleis changing, which varies the total amount of target analyte in the sample, aswell as the absorption properties of the sample. The sample states are produced,for instance, by compressing and uncompressing the tissue sample. The accuracyof the presented method is enhanced. by including continuous estimation of theamount of the fluid containing the target analyte within the sample, and measurementof the variations of the absorption at a wavelength at which the target analyteabsorbs significantly. The method is particularly useful in measuring the concentrationof a target analyte, such as glucose, in tissue containing blood. An apparatusfor performing this method also is disclosed.