Two papers appearing in the journals Nature Communications and Nature Nanotechnology describe portable devices that combine microfluidic technology with nuclear magnetic resonance (NMR) to not only diagnose these important infections but also determine the presence of antibiotic-resistant bacterial strains.
On this 2.5- by 7.5-cm cartridge, DNA extracted from sputum samples is amplified in the chambers on the left. TB-specific sequences are magnetically labeled in the microfluidic mixing channels in the center and detected by passage through the micro-NMR coil on the right.
Credit: Center for Systems Biology, Massachusetts General Hospital
"Rapidly identifying the pathogen responsible for an infection and testing for the presence of resistance are critical not only for diagnosis but also for deciding which antibiotics to give a patient," says Ralph Weissleder, MD, PhD, director of the MGH Center for Systems Biology (CSB) and co-senior author of both papers. "These described methods allow us to do this in two to three hours, a vast improvement over standard culturing practice, which can take as much as two weeks to provide a diagnosis."
Investigators at the MGH CSB 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, and the sample is then passed through a micro NMR system capable of detecting and quantifying levels of the target. But 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 the team switched to targeting specific nucleic acid sequences.
The system described in the Nature Communications paper, published on April 23, detects DNA from the tuberculosis bacteria in small sputum samples. After DNA is extracted from the sample, any of the target sequence that is present is amplified using a standard procedure, then captured by polymer beads containing complementary nucleic acid sequences and labeled with magnetic nanoparticles with sequences that bind to other portions of the target DNA. The miniature NMR coil incorporated into the device – which is about the size of a standard laboratory slide – detects any TB bacterial DNA present in the sample.
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 three hours. Existing diagnostic procedures can take weeks to provide results and can miss up to 40 percent of infected patients. Results were even stronger for patients infected with both TB and HIV – probably because infection with both pathogens leads to high levels of the TB bacteria – and specialized nucleic acid probes developed by the research team were able to distinguish treatment-resistant bacterial strains.
The Nature Nanotechnology paper, being issued online today, describes a similar system using ribosomal RNA (rRNA) – already in use as a bacterial biomarker – as a target for nanoparticle labeling. The investigators developed both a universal nucleic acid probe that detects an rRNA region common to many bacterial species and a set of probes that target sequences specific to 13 clinically important pathogens, including Streptococcus pneumoniae, Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA).
The device was sensitive enough to detect as few as one or two bacteria in a 10 ml blood sample and to accurately estimate bacterial load. Testing the system on blood samples from patients with known infections accurately identified the particular bacterial species in less than two hours and also detected two species that had not been identified with standard culture techniques.
While both systems require further development to incorporate all steps into sealed, stand-alone devices, reducing the risk of contamination, Weissleder notes that the small size and ease of use of these devices make them ideal for use in developing countries. "The magnetic interactions that pathogen detection is based on are very reliable, regardless of the quality of the sample, meaning that extensive purification – which would be difficult in resource-limited setting – is not necessary. The ability to diagnose TB in a matter of hours could allow testing and treatment decisions within the same clinic visit, which can be crucial to controlling the spread of TB in developing countries."
Hakho Lee, PhD, of the MGH Center for Systems Biology. co-senior author of both papers, notes that the system will alsohave important applications in developed countries. "The capacity of the system not only to identify bacterial species but also to differentiate factors such as antibiotic resistance will help clinicians treat patients with the 'right' drugs from the start, which also helps reduce the emergence of treatment-resistant strains. The fact that this device requires only a tiny drop of the sample to be tested will be helpful in instances when specimens can be hard to obtain, such as treating children or seniors."
Weissleder is a professor of Radiology, and Lee is an assistant professor of Radiology at Harvard Medical School. Co-lead authors of the Nature Communications paper are Monty Liong, PhD, of the MGH CSB and Anh Hoang, PhD, of the MGH Center for Engineering in Medicine; co-authors include investigators from Harvard School of Public Health and the Broad Institute. Hyun Jung Chung, PhD, of the MGH CSB is lead author of the Nature Nanotechnology report.
Support for both studies includes National Institutes of Health grants R01EB004626, R01EB010011, R01HL113156, P41EB002503, HHSN268201000044C, R01HL113156 and T32CA79443. The MGH has applied for patents on the technology described in this paper.
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."
Sue McGreevey | EurekAlert!
Further reports about: > Bird Communication > Broad Institute > DNA > Escherichia coli > MGH > Medical Wellness > Nanotechnology > Nature Immunology > Nature Nanotechnology > Portable breast scanner > bacterial species > bacterial strains > blood sample > cancer biomarker > developing countries > health services > magnetic nanoparticles > neurodegenerative disorder > nucleic acid sequence > radiology > resistant bacteria > synthetic biology
Bioinspired nanoscale drug delivery method developed by WSU, PNNL researchers
10.01.2019 | Washington State University
How herpesviruses shape the immune system
09.01.2019 | German Center for Infection Research
Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.
It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:
The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.
One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...
Just in time for Christmas, a Mars-analogue mission in Morocco, coordinated by the Robotics Innovation Center of the German Research Center for Artificial Intelligence (DFKI) as part of the SRC project FACILITATORS, has been successfully completed. SRC, the Strategic Research Cluster on Space Robotics Technologies, is a program of the European Union to support research and development in space technologies. From mid-November to mid-December 2018, a team of more than 30 scientists from 11 countries tested technologies for future exploration of Mars and Moon in the desert of the Maghreb state.
Close to the border with Algeria, the Erfoud region in Morocco – known to tourists for its impressive sand dunes – offered ideal conditions for the four-week...
Research opens doors in photonic quantum information processing, optical signal processing and microwave photonics
Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new integrated photonics platform that can...
A team of experimentalists at the U.S. Department of Energy's Ames Laboratory and theoreticians at University of Alabama Birmingham discovered a remarkably long-lived new state of matter in an iron pnictide superconductor, which reveals a laser-induced formation of collective behaviors that compete with superconductivity.
"Superconductivity is a strange state of matter, in which the pairing of electrons makes them move faster," said Jigang Wang, Ames Laboratory physicist and...
14.01.2019 | Event News
12.12.2018 | Event News
10.12.2018 | Event News
15.01.2019 | Life Sciences
15.01.2019 | Information Technology
15.01.2019 | Materials Sciences