A High Throughput Biofilm Assay System

DESCRIPTION (provided by applicant): A biofilm is an accumulation of microorganisms (e.g. bacteria, fungi, etc.) embedded in a polysaccharide matrix and adherent to a solid substrate. Biofilms are of particular interest in the clinical sciences, as they account for over 80% of microbial infections in the body. These infections can present themselves in the oral cavity, gastrointestinal tract, urogenital tract, and in the lung tissue of cystic fibrosis patients. Despite their widespread prevalence, biofilms remain a very difficult target to study in-vitro, and this has severely limited the development of effective anti-microbial drug compounds. Fluxion Biosciences proposes a high throughput instrument for biofilm analysis. This is a Phase 2 application, following successful completion of the great majority of milestones in the Phase 1 feasibility study. Based on the Company's unique microfluidic technology platform, the instrument would be capable of running 48 simultaneous biofilm experiments under continuous flow. The results will be assayed using standard microplate readers for improved throughput. This represents a considerable breakthrough over existing technologies, which are largely confined to singe-test experiments or well-plate assays with lower physiological relevance. Fluxion's approach involves coupling the advantages of flow-cell chambers (high biological relevance) with the convenience and throughput of traditional well plates. The resultant product will deliver a fully automated platform for biofilm research and anti-microbial drug discovery. Along with convenience and throughput, this system will deliver powerful features specific to biofilm analysis and drug discovery. These include a microfluidic dilution system for performing multiplexed dose-response analyses on anti-microbial compounds. The proposed system will be a simple to use, automated benchtop platform which will have a significant impact on the study of biofilms, the disease conditions where they are found, and the drug compounds which are needed to address them in the clinical setting. PUBLIC HEALTH RELEVANCE: Biofilms account for over 80% of microbial infections in the human body, and are a primary determinant in infections found in the oral cavity, gastrointestinal tract, urogenital tract, and lung tissue of cystic fibrosis patients. Despite their widespread clinical impact, testing of antibiotic compounds against bacteria in the biofilm state is a recent development, and the scientific instrumentation and screening tools available to study biofilms are severely limited. Researchers are limited to low throughput single test experiments, or well-plate based assays with much lower clinical significance because of limits of flow based systems that apply physiological shear and nutrient delivery. Fluxion Biosciences' proposes a way to perform biofilm assays using a microfluidic format which can deliver higher throughput while maintaining its biological relevance. This Phase 2 application is aimed at developing a fully automated robotic screening station in order to determine the efficacy of antibiotic compounds as applied to biofilms.