Chip-based technology used to diagnose tuberculosis

According to the World Health Organization (WHO), each year there are approximately three million undiagnosed cases of tuberculosis (TB) globally. Now, thanks to an industry–academia partnership between St George’s, University of London and medical technology company QuantuMDx, scientists have developed a cheap, rapid and portable diagnostic test to analyse sputum samples for Mycobacterium tuberculosis (Mtb) from suspected TB patients — a breakthrough that holds promise for improving TB detection and treatment of patients in high-endemic, under-resourced areas.

“Although it [TB] is infectious, it is highly treatable,” said lead investigator Dr Philip D Butcher. “However, affordable diagnostics suitable for implementation at the point of care are needed to reach the ‘missing millions’. Our TB research group at St George’s has a longstanding appreciation of the global imperative for improved diagnostics for TB, and we realised that novel technologies may provide an answer. We saw an opportunity by collaborating on a new chip-based technology using dielectrophoresis to selectively isolate Mtb bacilli from sputum samples.”

The investigators utilised a prototype microfluidic lab-on-a-chip system called CAPTURE-XT from QuantuMDx that can process solubilised sputum from suspected TB patients, capture Mtb bacilli for visual analysis (as a substitute for smear microscopy) and provide a purified sample for molecular confirmation by quantitative PCR (qPCR) and ultimately for genotypic drug-susceptibility analysis. CAPTURE-XT technology relies on the principle of dielectrophoresis — a little-utilised technique that can be tuned to selectively attract or repel specific particles or cells based on their dielectric properties. In this case, it is the Mtb bacteria that cause TB that are specifically captured and concentrated, while the other sputum contents are washed away.

After optimisation using a panel of 50 characterised sputum samples, the performance of the prototype was assessed by a blinded screening of 100 characterised and bio-banked sputum samples. Concordance with culture diagnosis was 100% for smear negative samples and 87% for smear positive samples. Of the smear positive samples, the high burden sample concordance was 100%.

These results, published in The Journal of Molecular Diagnostics, demonstrate the potential of the technology to provide a powerful sample preparation tool that could function as a front-end platform for enhanced molecular detection. The versatile tool could equally be applied as a visual detection diagnostic, potentially associated with bacterial identification for low-cost screening.

“The CAPTURE-XT technology is truly revolutionary and will have an impact in many different diseases from sepsis to oncology (circulating tumour cells),” said Dr Jonathan O’Halloran, founder and CEO of QuantuMDx Group. “This application in Mtb is truly exceptional as its ultralow cost and ultrahigh 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 visualised 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.”

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