Method for generating a net analyte signal calibration model and uses thereof

A method for non-invasively measuring the concentration of an analyte in a test subject, comprising:

• (a) identifying a test subject in need of having an analyte concentration measured;
• (b) generating an in vivo net analyte signal calibration model by:
• i) providing a set of in vivo infrared spectra for a test subject during a period in which an analyte concentration is essentially constant;
• ii) calculating an optimal subspace of spectra that at least substantially describes all non-analyte dependent spectral variance in the in vivo spectra of step i);
• iii) providing a pure component infrared spectrum for the analyte;
• and
• iv) calculating the net analyte signal spectrum from a data set comprising the optimal subspace spectra of ii) and the pure analyte spectrum of iii), wherein the net analyte signal spectrum identifies one or more in vivo spectral features specific to the analyte;
• (c) providing an in vivo infrared spectrum of the test subject;
• and
• (d) calculating a predicted concentration of the analyte in the test subject from a data set comprising the net analyte signal calibration model and the in vivo infrared spectrum of the test subject.