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We develop a label-free fluorescence method for ultrasensitive detection of apoptosis-associated caspase activity based on branched rolling circle amplification. This work demonstrates for the first time the use of a nucleic acid amplification strategy for the amplified detection of caspase activity, which allows for highly sensitive detection of endogenous caspase even at the single-cell level. This method can be further applied for kinetic analysis and inhibitor screening.In this work, an Eu2+-doped K3ScSi2O7 (KSSO) NIR phosphor with