Self-powered rapid antigen-specific T-cell response assay for Mycobacterium tuberculosis infections
Interferon-gamma release assays (IGRAs) that evaluate an individual's T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater diagnostic sensitivity in individuals with HIV-1 co-infections (93.8% versus 67%), comparable diagnostic sensitivity in HIV-negative individuals (92.8%) and faster detection (4 h versus 24-48 h). We also find that a self-powered ASTRA chip that analysed microsample (~25 μl) whole-blood samples produced comparable results. ASTRA holds the potential to facilitate efforts to control the global TB epidemic and serve as a versatile platform for analysing T-cell responses across various infectious diseases and immunotherapeutic interventions.
Authors
- Riti Sharan (ORCID: https://orcid.org/0000-0002-8297-6634)
- Sutapa Chandra (ORCID: https://orcid.org/0000-0002-4873-0921)
- Yongchun Pan (ORCID: https://orcid.org/0000-0001-9567-657X)
- Christopher J. Lyon (ORCID: https://orcid.org/0000-0003-2319-2933)
- Alexander Kay (ORCID: https://orcid.org/0000-0001-5283-4697)
- Anna M. Mandalakas (ORCID: https://orcid.org/0000-0002-8091-3509)
- Clement Gascua Adu-Gyamfi (ORCID: https://orcid.org/0000-0002-3190-9343)
- Gugu Maphalala (ORCID: https://orcid.org/0000-0002-3635-8405)
- Bo Ning (ORCID: https://orcid.org/0000-0001-9437-7244)
- Wu Qingli
- Edward A. Graviss (ORCID: https://orcid.org/0000-0003-1024-5813)
- Santiago Carrero Longlax (ORCID: https://orcid.org/0000-0001-8731-0105)
- Andrew R. DiNardo (ORCID: https://orcid.org/0000-0001-5990-6470)
- Ngan P. Ha
- Lin Li (ORCID: https://orcid.org/0000-0003-1839-8048)
- Ye Hu (ORCID: https://orcid.org/0000-0001-7255-5409)
- Sanjay Singh (ORCID: https://orcid.org/0000-0003-4601-5673)
- Smriti Mehra (ORCID: https://orcid.org/0000-0002-7942-0010)
- Alexandra Portillo Varela
Institutions
- Tulane University (US)
- Texas Biomedical Research Institute (US)
- Houston Methodist (US)
- Ochsner Health System (US)
- Baylor College of Medicine (US)
- Children’s Foundation (GB)
- Ministry of Health (SZ)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1038/s41551-025-01441-5
- Citations
- 4
- Primary Topic
- Advanced Nanomaterials in Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 2.07
Funders
- U.S. Department of Defense
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development