We present highly sensitive optical biosensors able to be fully integrated in lab-on-a-chip microsystems using standard CMOS compatible processes. These optical biosensors are based on integrated Mach–Zehnder interferometers, which have been designed to have high surface sensitivity and monomode behaviour. As a biosensing application of the devices we show the real-time detection of the covalent immobilization and hybridization of DNA strands without labelling. In order to achieve a lab-on-a-chip portable microsystem, we present the integration of the sensor with a CMOS compatible microfluidic system using SU-8 photolithography patterned layers.