Abstract This paper presents the development of a biosensor based on long period fiber grating, using a polyclonal antibody (OPN5) as a biological recognition element, which enables the detection of opsin (Opn5) in the brain tissue of a murine model with high specificity. Opsin (Opn5) is overexpressed in brain, ovarian, breast and prostate carcinomata and it may function as an important new biomarker to diagnose and monitor several types of cancer. In this study, the fiber surface was chemically prepared for antibody immobilization. The structural homogeneity of the biosensor was characterized by Fourier-transform infrared spectroscopy at each stage of the self-assembling process, and the response changes were measured by a signal transmission at the biosensor output. The biosensor developed was tested to detect Opn5 in brain tissue, and the interaction of Opn5 was observed through the evolution of the transmission spectrum in real time. Finally, the transmission data were analyzed by a principal component analysis (PCA).