A method and apparatus for non-invasively measuring animal/human blood glucose and other metabolites including an excitation laser source, a negative pressure based sampling port which interfaces to a human or other animal tissue sample in vivo, a Raman spectrometer, and data analysis and display devices. The device can be made in a compact size and may be portable, and it can be used in homes, offices or clinics. A negative atmospheric sampling port is made of a vacuum chamber that is connected with an electrically or manually driven vacuum pump which creates a negative air pressure inside the vacuum chamber. Under the negative air pressure, a substantial amount of blood is "sucked" into a small area of the human finger so that measurement of an enhanced Raman signal can be made.