1. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org 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

2. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org 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

3. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org 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 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.

4. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org 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)

5. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org Isolation of M. tuberculosis Lipoarabinomannan (LAM) from urine of TB patients using an antibody-based microfluidic detection platform TB Detection Project 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.

6. Indiana CTSI ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH Indiana C linical and T ranslational S ciences I nstitute www.indianactsi.org 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.