Today, the search for disease biomarkers and techniques for their detection is one of the most important focuses in modern healthcare. Extracellular vesicles (EVs) are known to be related to the pathogenesis of various illnesses, such as cancer, neurodegenerative disease, and cardiovascular disease. Specific EV detection and potential control of their amount in biological fluids can provide a promising therapeutic strategy that involves reduction in EV production and circulation to normal levels to prevent disease progression. To provide a foundation for such research and development, we report the application of photonic integrated circuits in the form of a Mach–Zehnder interferometer coupled with microfluidics for monitoring each step of a covalent linkage between receptors and silicon nitride. We show that such a biosensor can be used for biological marker quantification, such as EVs containing a specific membrane protein HER2. The developed platform provides real-time results by using microliter volumes of the test sample. This research can be used as a first step toward creation of a laboratory on a chip for the precise control of coating in terms of chemical applications and monitoring the effectiveness of the chosen treatment for medical applications.