Food allergens cause worldwide chronic diseases with a great impact on public health. Immunoglobulins E (IgEs) trigger allergic reactions by specifically binding the allergens to which the allergic patients are sensitized. In this scientific work we report for the first time a new optical interferometric in vitro system for the detection of specific IgEs (sIgEs) to the principal peach allergen (Pru p 3) in real serum samples. Interferometric Optical Detection Method (IODM) was employed for reading out the signal of Fabry-Perot based interferometers acting as biotransducers. Pru p 3 was immobilized as bioreceptor onto the sensing surface for detecting the target biomolecules, sIgEs to Pru p 3. Moreover, the demanding low concentration of IgE, compared to other analytes in real serum samples, made it necessary to use nanoparticles (NPs) for two reasons: to collect only the IgEs from the serum sample and to enhance the optical interferometric read-out signal. The methodology was validated in advance by scanning electron microscopy (SEM). Consequently, we report in this article a novel high-performance in vitro detection method to recognize sIgE to molecular allergens by means of silicon dioxide (SiO) NPs. Finally, this scientific work provides the basis for the in vitro component resolved diagnosis (CRD) of sIgEs to molecular allergens.Copyright © 2020 Elsevier B.V. All rights reserved.