Lipopolysaccharide Imprinted Polymers for Specific Recognition of Bacterial Outer Membrane Vesicles

Outer membrane vesicles (OMVs) secreted by bacteria are emerging diagnostic markers for bacterial infection or disease detection due to their carriage of various signaling molecules. However, actual biological samples of patients are extremely complex, and applying OMVs to clinical diagnosis remains a major challenge. One of the major challenges is that there are still great difficulties in the enrichment of OMVs including tedious steps and lower concentration. And some commonly used exosome enrichment methods, such as ultracentrifugation, still have some shortcomings. Herein, we introduce lipopolysaccharide (LPS) molecularly imprinted polymer (MIP) for efficient capturing and analyzing OMVs, enabling a novel approach to bacterial disease diagnosis based on biorecognition materials. LPS, as a unique structure of Gram-negative bacteria, also widely expressed on the surface of OMVs, which will form cyclic hydrogen bonds with functional monomers of MIP with affinity interactions. The prepared MIP efficiently can isolate OMVs from 100 μL of culture broth via specific affinity LPS in less than 40 min with a recovery rate of over 95%. Moreover, MIP exhibits good reusability, with almost identical enrichment performance after 5 repeated cycles, contributing to reducing experimental costs in both time and economy. The captured OMVs can be detected using Western blotting with target protein antibodies or in combination with proteomic analysis, providing a proteomic biomarker platform for early bacteria disease diagnosis.