In a noninvasive system for detection/measurement of glucose and other analytes in a medium such as tissue, illumination is directed to the medium and corresponding radiation from the medium is collected. Spectral energy changes associated with fragment(s)/feature(s) obtained from the collected radiation are determined using collision computing. Such spectral energy changes generally represent analyte concentration. The illumination is controlled to target a particular volume of the medium and/or such that the spectral energy changes become directionally monotonic with respect to analyte concentration. The illumination parameters include: intensity, wavelength, bandwidth, focal length, and/or duration of illumination, location and/or a size of an illuminated spot on the medium surface, depth at which the illumination can reach below the medium surface, spacing between the illuminated spot and a spot on the medium surface from which radiation is collected, and angle of the illumination relative to the medium surface.