A Quencher‐Based Blood‐Autofluorescence‐Suppression Strategy Enables the Quantification of Trace Analytes in Whole Blood

Abstract Precise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence‐suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood. Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPY quencher with an absorption wavelength ranging from 600–700 nm was selected for its superior quenching efficiency and high brightness. Two 7‐nitrobenzoc 1,2,5 oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H 2 S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal‐to‐back ratio, the probe thus achieved the accurate quantification of endogenous H 2 S in 20‐fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H 2 S in whole blood. Moreover, this autofluorescence‐suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.