The EU-funded NOMBIS project developed nano-optomechanical disk resonators (see photo for disk with one bacterium) for early identification of infection-causing pathogens. These devices can be configured to measure and identify, with extreme sensitivity, for a wide variety of chemical or biomolecular sensing applications.
Weighing DNA and RNA: A future identity parade for microbes
“We have applied nano-optomechanical disk resonators to biosensing, achieving ultra-sensitive and ultra-fast biomolecule detection with zeptogram mass resolution in a fluid environment,” outlines Dr Eduardo Gil-Santos, project coordinator. A zeptogram is an incredibly small mass, a sextillionth of a gram in fact. NOMBIS researchers have developed arrays of hundreds of microdrum devices per chip. These can weigh DNA strands complementary to those immobilised on the microdrum surface. Many different pathogens in a blood sample can therefore be identified, along with antibiotic resistances, which are marked by mutations. An enormous challenge was the detection of bacteria by targeting the 16S ribosomal RNA gene. It can be used for identification as different bacteria have varying numbers of copies of this gene. “Nano-optomechanical disk resonators are excellent devices to detect individual, intact and alive bacteria,” explains Dr Gil-Santos. Not only do they quantify mass, they can also detect the intrinsic mechanical resonances of the bacteria, which could provide a unique signal for their identification. Bacteria commonly responsible for sepsis were targeted in particular as delay in treatment can result in septicaemia and organ failure. “We have tested our devices with two common pathogens: Staphylococcus epidermidis and Escherichia coli,” points out Dr Gil-Santos. These bacteria are part of the normal human flora and normally not pathogenic, but may become so in immunocompromised patients.
Problems encountered at sub-zeptogram levels
An essential condition for detection is that the sensor and the analyte mode have close resonant frequencies. “As a result, we had to fabricate many disk resonators and change their dimensions to arrive at the correct frequencies. These were then matched with those in the analyte,” explains Dr Gil-Santos. Testing in the devices must be efficient. To ensure this, the team developed a pathogen deposition system, which enables them to place individual analytes in the sensors with micrometre precision.
On the road to commercialisation
The establishment of mechanical spectroscopy as a reference technology in biomedicine requires detection, not only of single modes, but the entire mechanical spectra of the analytes, ideally, in physiological conditions. Going on to explain what is required for this groundbreaking technology, he elaborates: “Progress up to now has demonstrated that mechanical sensors can detect single mechanical modes of analytes in air, which was never done before, let alone proposed.” The team has applied for a European Research Council Starting Grant to further work on mechanical spectroscopy. The project has generated an international patent. “Now, I am looking for companies interested in commercially exploiting this idea. However, the concept is completely new so it will require further advances to be completely established,” Dr Gil-Santos points out. Ultimately, spectroscopy will enable detection of pathogens and also monitor in real time their mechanical and morphological properties with extraordinary precision. As well as saving lives with timely application of currently available drugs, the technique will further the development of novel drugs.
NOMBIS, mechanical, detection, bacteria, pathogen, nano-optomechanical disk resonator, sensor, microbe, RNA, biomolecule, gene, mechanical spectroscopy