Diagnosis of prosthetic joint infection based on Cas12a-catalytic aggregation mediated by supramolecular chemistry

Prosthetic joint infection (PJI), which is still difficult to be diagnosing, is caused by bacterial infection. Rapid detection for trace amounts of bacteria should be a solution; however, the existing assays cannot serve for PJI diagnosis due to the inherent limitations. Herein, a strategy based on supramolecular chemistry mediated Cas12a catalytic aggregation (CCA) is explored in this work for ultrasensitive detection of universal bacteria. In the design, supramolecular chemistry is introduced to impede the cis-cleavage of activated Cas12a, resulting in its aggregation in the surrounding of bacteria with the linkage of CCA probe. Since Cas12a aggregation owns excellently enhanced catalytic efficiency, the CCA-based strategy can be used for bacterial analysis with a limit of detection as low as 1 CFU/mL. With high sensitivity, reproducibility, generalizability, and stability, the CCA-based strategy can be applied for the detection of clinical effusion samples. The remarkable performance of CCA-based strategy has also demonstrated its robust potential to be a simple, rapid, and highly sensitive bacteria diagnostic tool, paving the way for prompt diagnosis and management of PJI.