The program is aimed at applying an ultra-sensitive magnetic detection platform to the rapid and early diagnosis of pathogens causing sepsis. The technology platform is based on labeling biomolecules with magnetic nanoparticles and detecting the magnetic field generated upon binding using patented ultra-sensitive magnetic sensors. ? ? While the initial focus will be on a """"""""proof-of-principle"""""""" demonstration for the direct detection of two major ? pathogens, Staphylococcus aureus and Escherichia coli, responsible for sepsis, the diagnostic platform ? should be generally applicable to a wide range of pathogens. ? ? Direct detection of live bacteria will be demonstrated by measuring the binding of magnetic labeled ? antibodies to a surface antigen on the target pathogen. Purchased bacteria will first be used to ? demonstrate a proof-of-concept for high sensitivity in a rapid, """"""""mix and measure"""""""" magnetic assay. A next generation prototype instrument will then be produced and placed at our collaborator, Children's Hospital Boston. An existing IRB-approved library of clinical specimens with documented infections (600 blood and urine samples, 150 trachea) aspirates) will be examined in order to demonstrate clinical utility, including sensitivity, specificity and short assay times. ? ? The ultimate goal of this program is to show a limit of detection < 100 bacteria/ml in clinical samples with a total (preparation and measurement) assay time of less than 15 minutes. Additionally, detection limits as low as 5-10 bacteria in small samples (e.g., 20 ul) may be possible by using the unique ability to externally manipulate magnetic nanoparticle labels using magnetic fields. Note that magnetic detection is not hampered by measurement in biological fluids and the mix and measure format in microplate wells requires little sample preparation, thereby minimizing errors. ? ? ?
