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In this study, the authors investigate one of the biological sensory applications (fluorescence resonance energy transfer (FRET)) that has astonishing influence on implementation of the bio-medical assays. For the first time, in this study, the new inorganic modified nanoparticle structure (quantum-dot quantum-well (QDQW) heteronanocrystal) is used as donor particle. By considering the mentioned structure, the authors can easily manipulate the donor emission spectrum and all parameters of FRET, such as overlapping between the donor emission and acceptor absorption. In this procedure, the F??rster radius can be completely controlled. Moreover, the quantum confinement effects, including the strong-confinement and the weakconfinement regime, are investigated for FRET essential variables. As a main goal of this study, the authors will mathematically explore the influences of perturbation on the intrinsic parameters of nanoparticles (lifetime and bandwidth of emission spectrum) and on the sensitivity of FRET. It can be revealed that the presence of perturbation in nanoparticle has a devastating influence on biological assay characteristics, which will be probe in presented simulations. Furthermore, the physically analysing of QDQW heteronanocrystal structure is performed by the accurate eight-band K.P theory and finiteelement method.