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Photon upconversion is an intensively investigated phenomenon in the materials sciences due to its unique applications, mainly in biomedicine for disease prevention and treatment. This study reports the synthesis and properties of tetragonal LiYbF 4 :Tm 3+ @LiYF 4 core@shell nanoparticles (NPs) and their applications. The NPs had sizes ranging from 18.5 to 23.7 nm. As a result of the energy transfer between Yb 3+ and Tm 3+ ions, the synthesized NPs show intense emission in the ultraviolet (UV) range up to 347 nm under 975 nm excitation. The bright emission in the UV range allows for singlet oxygen generation in the presence of hematoporphyrin on the surface of NPs. Our studies show that irradiation with a 975 nm laser of the functionalized NPs allows for the production of amounts of singlet oxygen easily detectable by Singlet Oxygen Sensor Green. The high emission intensity of NPs at 800 nm allowed the application of the synthesized NPs in an upconversion-linked immunosorbent assay (ULISA) for highly sensitive detection of the nucleoprotein from SARS-CoV-2, the causative agent of Covid-19. This article proves that LiYbF 4 :Tm 3+ @LiYF 4 core@shell nanoparticles can be perfect alternatives for the most commonly studied upconverting NPs based on the NaYF 4 host compound and are good candidates for biomedical applications., Competing Interests: Declaration of Competing Interest The authors do not declare any competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)