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Mycobacterium tuberculosis. One third of the world population is currently infected. Over 8 million new cases of TB in 2007. 5-10% of those infected become sick or infectious at some time in their lives. An estimated 1.6 million TB deaths occurred in 2007 . Drug-resistance is on the rise
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Mycobacterium tuberculosis • One third of the world population is currently infected. • Over 8 million new cases of TB in 2007. • 5-10% of those infected become sick or infectious at some time in their lives. • An estimated 1.6 million TB deaths occurred in 2007. • Drug-resistance is on the rise • No effective vaccine against pulmonary TB www.who.int
Lines of Investigation– Schorey laboratory • Molecular and cellular basis of TB pathogenesis. • Exosomes as TB vaccine candidates • Diagnostic tools for TB. Supported by: National Institutes of Health - R01 AI056979 - R01 AI052438 Gates Exploration Grant
Diagnostic needs: High specificity and sensitivity as well as a test which is rapid, requires minimum manipulation, easy to use and is of minimal cost. • What is available: • Acid-fast smear test using sputum • Culturing approaches using sputum as the source of bacilli • Detection from patient blood antibodies or T cells specific for • mycobacterial components • Detection of M.tb DNA or RNA in patient bodily fluids or sputum • Detection of other mycobacterial components in patient bodily fluids
TB Diagnostic Development Through Research and Industrial Collaboration • Indiana Clinical and Translational Sciences Institute (ICTSI) • University of Notre Dame’s College of Engineering and College of Science • Advanced Diagnostics and Therapeutics and the Eck Institute for Global • Health • Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH) • and the IU School of Medicine • Companion Diagnostics Inc. • Sony DADC (Polymer Devices Branch of SONY)
TB Detection Project Isolation of M. tuberculosis Lipoarabinomannan (LAM) from urine of TB patients using an antibody-based microfluidic detection platform • Couple LAM antibodies to chip/sensor substrate using • micro-stamping techniques. • Converting current glass microfluidic platform to hard plastic, • including synthesis of on-chip membranes • Develop and assemble hand-held chip reader and design • large-scale hard polymer chip production methods. • Test chip prototypes first using urine “spiked” with LAM, then urine • samples from TB patients (Kenya) and control samples.
Detection Platform An open-flow impedance-sensing platform for LAM binding to a antibody functionalized carbon nanotube surface in the presence of a high-frequency AC electric field.