Tuberculosis Diagnosis With Handheld Device

Portable devices that combine microfluidic technology with nuclear magnetic resonance (NMR) testing can rapidly diagnose tuberculosis (TB) and other important bacterial infections, as well as determine the presence of antibiotic-resistant bacterial strains.

“Rapidly identifying the pathogen responsible for an infection and testing for the presence of resistance is critical not only for diagnosis but also for deciding which antibiotics to give a patient,” said Ralph Weissleder, MD, PhD, Director of the Massachusetts General Hospital Center for Systems Biology and Professor of Radiology at Harvard Medical School in Boston.

Dr Weissleder is the senior coauthor of 2 new papers that describe the handheld diagnostic device.
 
“Standard culture methods for bacteria take days or weeks, especially for Mycobacterium tuberculosis, to complete, and require stringent conditions to prevent contamination,” Dr Weissleder told ConsultantLive. “The NMR device can give accurate results within 2.5 hours and uses an inexpensive, disposable container to prevent contamination.”

The new system is designed to reduce the emergence of treatment-resistant bacterial strains.

Dr Weissleder said, “Since the NMR device can identify the drug-resistant strains in 2.5 hours, patients can be given accurate treatments on the same day, which will help reduce the emergence of these strains.”

Dr Weissleder and colleagues had previously developed portable devices capable of detecting cancer biomarkers in the blood or in very small tissue samples. Target cells or molecules are first labeled with magnetic nanoparticles. The sample is then passed through a micro NMR system capable of detecting and quantifying levels of the target.

Initial efforts to adapt the system to bacterial diagnosis had trouble finding antibodies-the detection method used in the earlier studies-that would accurately detect the specific bacteria. Instead, Dr Weissleder’s team switched to targeting specific nucleic acid sequences.
 
Tests of the device on samples from patients known to have TB and from healthy controls identified all positive samples, with no false positives, in less than 3 hours. Dr Weissleder noted that existing diagnostic procedures can miss up to 40% of infected patients.

Results were even stronger for patients infected with both M tuberculosis and HIV, probably because infection with both pathogens leads to high levels of M tuberculosis, Dr Weissleder said. Specialized nucleic acid probes developed by the research team were able to distinguish treatment-resistant bacterial strains.

Dr Weissleder noted that this device requires only a tiny drop of the sample to be tested, which will be helpful in hard-to-obtain specimens, for example, from children or seniors. “We have already tested the device on clinical patient samples and will continue to analyze more samples,” he said. “We are finalizing the automated sample processing component that can isolate the bacteria and nucleic acids from patient samples and will complete it by next month.”

“Nucleic acid amplification tests will continue to be one of the most effective tools in identifying and preventing bacterial infections,” Dr Weissleder noted.

The researchers reported their results in the April 23 issue of Nature Communications and online in the May issue of Nature Nanotechnology.