Abstract: A system and method of calibrating a model used in a device for non-invasive in vivo measurement of an analyte concentration using Raman spectroscopy, the device including an optical source for providing an optical signal and an optical detector to receive a Raman scattered optical output, the method including: in response to the laser source being directed to a user's skin gathering Raman scattered radiation from the user's skin and based on that, calibrating the model based on reference data and the received Raman spectra over an extended period of days, such as 10 days or more.