Cutting-Edge Device Diagnoses Tuberculosis in `Missing Millions`

Tuberculosis (TB) ranks as the 13th most common cause of death globally, and prior to COVID-19, it held the infamous title of the deadliest single infectious disease, claiming more lives than malaria and HIV. Every year, TB infects 10 million people worldwide and leads to 1.4 million deaths. The World Health Organization reports that approximately three million TB cases go undiagnosed each year, referred to as the "missing millions." To address this issue, there's a pressing need for affordable diagnostic tools that can be employed at the point of care. Now, a new diagnostic device utilizing chip-based technology and dielectrophoresis has shown a potential to enhance TB detection and patient care in high-risk, underprivileged regions, thereby contributing to the global effort to diminish the disease’s burden.

The development of this revolutionary diagnostic tool is a result of a unique collaboration between the TB research team at St George’s University of London (London, UK) and QuantuMDx (Tyne and Wear, UK). The researchers have created a prototype microfluidic lab-on-a-chip system called CAPTURE-XT to analyze sputum samples from individuals suspected of having TB for the presence of Mycobacterium tuberculosis (Mtb). The system can process solubilized sputum, isolate Mtb bacteria for visual examination, thereby substituting smear microscopy, and also offer a purified sample for molecular confirmation via quantitative PCR (qPCR) and for genotypic drug-susceptibility analysis. CAPTURE-XT operates on the principle of dielectrophoresis, a relatively underutilized technique that can be calibrated to selectively attract or repel specific particles or cells based on their dielectric properties. In this context, the technique specifically captures and concentrates Mtb bacteria, the causative agent of TB, while other components in the sputum are removed.

After fine-tuning the device with a panel of 50 characterized sputum samples, the prototype's efficacy was assessed through a blinded screening of 100 characterized and bio-banked sputum samples. The device demonstrated complete concordance with culture diagnosis for smear-negative samples and 87% concordance for smear-positive samples. Impressively, the concordance was 100% for high-burden smear-positive samples. These results show that this technology holds potential as a powerful sample preparation tool, which could serve as a front-end platform for improved molecular detection. The tool’s versatility could also allow it to be used as a visual detection diagnostic, potentially paired with bacterial identification for cost-effective screening.

“This new chip-based technology could bring diagnostics to the patients that need it and also, by more accessible case-finding, prevent the further spread of this disease,” said lead investigator Philip D. Butcher, PhD, St George’s, University of London.

“The CAPTURE-XT technology is truly revolutionary and will have an impact in many different diseases from sepsis to oncology (circulating tumor cells),” said Jonathan O’Halloran, PhD, founder and Chief Executive Officer of QuantuMDx Group Ltd. “This application in Mtb is truly exceptional as its ultra-low cost and ultra-high sensitivity will profoundly improve equitable access to quality diagnoses for hundreds of millions of people.”

“This chip-based technology exploits the physiological property of the TB bacteria to be specifically collected onto the device so that small numbers can be visualized on the chip electrodes and act as a visual readout to replace the lab-based sputum smear/microscopic methods, which typically have low detection rates and require training laboratory staff, at molecular-like sensitivities and at a fraction of the price. Moreover, when used as a front-end to downstream cellular, protein, and molecular devices, the possibilities are almost limitless,” added O’Halloran.

Related Links:
St George’s University of London
QuantuMDx