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Periodontal disease is a common inflammatory disease which erodes the supporting structures of the teeth, and is initiated by a subgingival infection with selected Gram-negative bacteria. Monoclonal antibodies (mAb) to lipopolysaccharide (LPS) of four periodontal pathogens, A. actinomycetemcomitans, P. intermedia, F. nucleatum and P. gingivalis were examined for specificity and their ability to bind these pathogens in a particle concentration fluorescence immunoassay (PCFIA). The mAb selected were specific for their homologous bacteria and when tested against a large battery of other bacteria, including 16 genera and 46 species, were found not to cross-react with heterologous species. When each of the mAb was challenged with 40 or more homologous freshly isolated bacteria, more than 90% were positive. Non-cellular antigens in the form of soluble LPS and extracellular vesicles were examined for their ability to bind to assay components and alter the apparent results of the assay. LPS was found to have potential as an interfering agent if bound to assay components prior to sample treatment, but this non-specific binding was significantly reduced when a surfactant was added to the buffers. Extracellular vesicles had no significant effect on the estimation of P. gingivalis by the assay.