We designed AGR2-aMB, with the following sequence: CGACGCACCGATCGCAGGTTCGGGATTTTCGGGTGG-GAGTTGTGGGGGGGGGTGGGAGGGTT-FAM, where the AGR2 binding region is underlined and the SA aptamer sequence is in bold. Stable hairpin structure is formed by intramolecular hybridization ( Figure S5 ). In our experiment, when only AGR2-aMB incubated with SA beads, no probe can bind to SA beads, and the beads fluoresced very weakly. In the presence of AGR2, however, the fluorescence intensity of SA beads increase significantly, suggesting the binding of AGR2-bound probe to SA beads. With the increase of AGR2 concentration, steady increases in fluorescence intensity on the target beads were observed. AGR2 at 100 nM concentration can be easily detected (Figure 6a) . A series of proteins including BSA, trypsin, thrombin, and IgG were employed as controls (500 nM), and no distinct fluorescent signals were observed (Figure 6b) , indicating an excellent specificity of the AGR2-aMB towards target molecule. The results demonstrated the sensitivity and specificity of the allosteric molecular beacon probe, implying its potential for application in real sample analysis, such as protein function study and disease diagnosis.