Sampling is controlled to enhance analyte concentration estimation derived
from noninvasive sampling. Means of assuring that the same tissue sample
volume is repeatably sampled are presented, thus minimizing sampling
errors due to mechanical tissue distortion, specular reflectance, and
probe placement. In a first embodiment of the invention, sampling is
controlled using automated delivery of a coupling fluid to a region
between a tip of a sample probe and a tissue measurement site in a manner
requiring minimal user interaction. In a second embodiment of the
invention, sampling is controlled by controlling temperature variations,
preferably with a coupling fluid, at a region about the tip of a sample
probe and a sample site. In a third embodiment, sampling is procedurally
controlled via timing and location of coupling fluid delivery to a sample
site.