The present invention discloses a method and apparatus and method for achieving non-invasive measurement of analytes from human and animal blood through the skin using Raman lightwave technology. The apparatus includes a confocal signal collection system that effectively reduces the interferences from out-of-focus signals. The apparatus further includes a tissue permeation unit, which controls the amount of blood in the laser tissue interaction region. The change of aggregate spectra with time is used to construct a new series of differenced spectra, from which the spectral effects from surrounding static substances are calibrated out dynamically using the data processing method described.