Abstract: The invention provides compositions, methods and devices for noninvasive measurement of the analyte levels in vivo. More specifically, the invention provides a hand-held glucose monitor and an optical coupler that allows for short-term discontinuous and/or continuous information on dynamic in vivo glucose levels. The device may include a optical coupler for optically connecting a skin surface to the device that contains a plurality of zones. These zones contain areas for a variety of purposes including calibration of the instrument, reading of the skin surface, and protection of the instrument.