Macro shot of a bombardier beetle on leaf. [seanjoh/ iStock / Getty Images Plus]
When threatened, the bombardier beetle launches a noxious chemical spray by combining two compounds in its abdomen—a natural defense mechanism that doesn’t require external power. It was this beetle’s ingenuity that inspired scientists to tackle one of the deadliest infectious threats today: tuberculosis (TB), especially in people living with HIV.
To circumvent the need for electricity in remote or resource-limited settings, researchers at Tulane University adapted the beetle’s chemistry into a new point-of-care diagnostic. Their innovation, called ASTRA (Antigen-Specific T-cell Response Assay), is a self-powered, handheld device that may outperform current diagnostics in detecting TB, particularly among immunocompromised populations.
“Nature has always been our greatest teacher,” Tony Hu, PhD, senior author of the study told GEN. The study, titled “Self-powered rapid antigen-specific T-cell response assay for Mycobacterium tuberculosis infections,” was published in Nature Biomedical Engineering. “Inspired by the ingenious defense mechanism of the bombardier beetle, we harnessed the power of bio-inspired nanotechnology to create ASTRA—a self-powered, portable device that revolutionizes tuberculosis detection. By mimicking the elegance of natural systems, we’ve overcome the limitations of traditional diagnostics.”
Tuberculosis remains the world’s deadliest infectious disease, claiming more than 1.2 million lives annually. While many infections are latent and symptom-free, individuals with HIV are at high risk of rapid disease progression. HIV suppresses the immune cells that TB tests typically rely on, making diagnosis especially difficult.
“TB is the [number] one pathogen HIV patients worry about globally,” said Hu, who holds the Weatherhead Presidential Chair in Biotechnology Innovation at Tulane and directs the Tulane Center for Cellular & Molecular Diagnostics. “If treatment is available, we should be working to kill these bacteria, latent or not.”
In clinical validation, the ASTRA device outperformed the widely used interferon-gamma release assay (IGRA), which depends on the patient’s CD4+ T cells to produce interferon-gamma (IFNγ). In people co-infected with HIV and TB, the ASTRA achieved 87% sensitivity, compared to IGRA’s 60%.
To achieve these results, the team sidestepped IFNγ and instead focused on surface activation markers OX-40 and 4-1BB, which are expressed by both activated CD4+ and CD8+ T cells. The dual-marker approach ensures diagnostic power even when CD4+ counts are low, as is common in advanced HIV.
“Tests dependent on IFNγ, whether IGRA, T-SPOT, or QuantiFERON, demonstrate sub-par performance among people infected with HIV (PLWH) and other anergic populations, such as adolescents with previous helminth infection,” the authors write. By focusing on activation markers detectable in a broader subset of T cells, ASTRA appears to overcome this bottleneck.
The ASTRA platform consists of a credit card–sized chip loaded with reagents that mimic a TB “wanted poster,” from a single drop of blood. After four hours of incubation, the built-in reaction—driven by a nanozyme-fueled chemical process—propels the sample through the chip without external power. Results are available within four hours, versus the 24–48 hours required by conventional IGRA, reported the researchers.
Validation studies were conducted using blood samples from Eswatini, a country with high TB incidence and the highest reported HIV-1 prevalence (27.3%). ASTRA was able to detect TB in nearly all HIV-positive individuals, including those who were anergic (lacking immune responses in standard tests).
“If your community has an immunocompromised population, someone may have latent TB,” said lead author Bo Ning, PhD, assistant professor at Tulane University School of Medicine. “This can help block the spread of TB and ensure that no one slips through the cracks.”
With its portability, affordability, and accuracy, ASTRA may be aligned with global efforts to eliminate TB by 2035, particularly in high-burden, low-resource settings. Its developers are already looking ahead to broader applications—including immunotherapy monitoring and point-of-care diagnostics for other diseases.
“Increasing testing accuracy, access, and speed is more vital than ever as TB drug resistance rises,” Hu said. “This is how we turn nature’s wisdom into life-saving innovation.”
