An apparatus for varying localized absorption and scattering coefficients at a tissue measurement site in a controlled and reproducible manner during optical sampling of a tissue volume by controlling the pressure applied to a tissue measurement site by a spectroscopic analyzer allows applied pressure to be maintained at a constant level, or the applied pressure may be varied in a controlled, reproducible manner as a function of time. A rest for receiving a body part holds the body part in a fixed position and at a fixed elevation. A mechanical system advances a fiber optic probe until it makes contact with the body part with a constant amount of pressure. The applied force is supplied by a counterweight on a single arm balance. A temperature control allows the temperature of the fiber optic probe to be equilibrated with the temperature in the immediate vicinity of the tissue measurement site. Alternate embodiments allow the fiber optic probe to be brought into direct contact with the tissue measurement site, and displaced a known distance into the tissue. The invention is also embodied as a method in which the absorption and scattering coefficients for successive spectral measurements are calculated to determine optimum depth of penetration for detection of a target analyte.