Systems and methods for determining an in vivo concentration of a small molecule substance of interest is provided that takes advantage of the semi-permeable nature of skin, which allows small molecules to passively diffuse through the skin and onto the skin surface. The systems and methods of the present invention allow for the collection of these small molecules that have passively diffused through the skin without skin disruption or breaking of the skin. The systems and methods of the present invention are noninvasive, painless and safe even for delicate newborns, and are particularly suited for the determination of blood glucose in newborns and infants in a noninvasive manner.
