Abstract: Embodiments of the present invention relate to a system and method for in vivo measurement of blood parameters by processing analog electrical signals from a plurality of photodetectors. In some embodiments, it is possible to determine one or more blood parameters according to (i) a first electrical signal from a first detector and (ii) a second electrical signal from a second photodetector. A difference analog electrical signal is generated, indicative of a difference between the light response signal at the first location and light response signal at the second location, is generated. One or more blood parameters may be detected according to the difference analog electrical signal.