Of all diseases, tuberculosis (TB) represents one of, if not, the greatest health disparity between whites and minorities [1]. For every TB-infected white person in the United States, there are an estimated 9 African- Americans, 8 Latinos, 6 Native Americans, 23 Asians, and 21 Native Hawaiian/Pacific Islanders with this disease [2]. Compounded with this disparity is the prevalence of drug-resistant mutations of TB, which have an associated 1000 polymorphisms that span 36 genes, two promoter regions, and one ribosomal RNA coding region [3]. Current methodologies, available primarily to affluent healthcare communities, utilize microbial cultures, which require sophisticated laboratories and weeks before a result can be determined. Difficulties for minorities in a low socioeconomic class to commute and/or follow up with their physicians can result in a lack of appropriate treatment. A low-cost, simple, and rapid point-of-care (POC) test that detects TB and its resistance to first-line drugs (isoniazid, rifampin, ethambutol,and pyrazinamide) would improve TB diagnostics for these minority communities. However, current technologies lack sensitivity, specificity, and/or multiplexing capacity to achieve this goal. We, therefore, propose to develop a POC device that offers the sensitivity of culture methods, specificity of nucleic acid methods, and a broad coverage of mutations. To accomplish this, we will advance our TruArray platform (hemispherical porous gel drop microarrays) for TB diagnostics using on-chip PCR and our existing MDR-TB PCR-microarray biochips. During Phase 1 we demonstrated feasibility of our sample preparation approach, our PCR-micorarray biochips, and prototype POC instrument. For Phase 2 we propose to expand the coverage of our test to include additional mutations that confer resistance to all first-line drugs, integrate this test onto our POC instrument, and translae this system to Laboratorios Medicos Especializados in Juarez, Mexico.

Public Health Relevance

Of all diseases, Tuberculosis (TB) represents one of, if not, the greatest health disparity between whites and minorities. To be specific, for every TB-infected white person in the United States, there are an estimated 9 African-Americans, 8 Latinos, 6 Native Americans, 23 Asians, and 21 Native Hawaiian/Pacific Islanders with this disease. The proposed project is to develop a point-of-care device for identifying drug-resistant strains of Tuberculosis that can be widely disseminated to minority populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44EB011274-03
Application #
8471603
Study Section
Special Emphasis Panel (ZEB1-OSR-B (J1))
Program Officer
Korte, Brenda
Project Start
2010-06-01
Project End
2016-05-31
Budget Start
2013-06-15
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$399,504
Indirect Cost
Name
Akonni Biosystems, Inc.
Department
Type
DUNS #
154704444
City
Frederick
State
MD
Country
United States
Zip Code
21701
Linger, Yvonne; Kukhtin, Alexander; Golova, Julia et al. (2014) Demonstrating a multi-drug resistant Mycobacterium tuberculosis amplification microarray. J Vis Exp :