ARCHIVED - Nanoprobes sniff out bad bugs

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December 21, 2009

Miniscule probes that can quickly identify dangerous bacteria such as Salmonella could allow faster, simpler disease diagnoses.

Dr. Arnold Kell demonstrates the use of a strong magnet to concentrate a pathogen sample collected with nanoparticles. An image of a sample is shown on the monitor behind him.

For five years, NRC chemists have been designing microscopic probes called “nanoparticles” to identify different types of pathogens faster and give epidemiologists a vital head start on containing disease outbreaks.

Faster detection would also help doctors avoid over-prescribing unnecessary “insurance” antibiotics before they obtain lab results from older, slower diagnostic tests. This would ultimately reduce the spread of antibiotic-resistant superbugs, making Canadians safer — and saving them money.

Microscopic nanoprobes comprise only a few thousand atoms, and measure only one nanometre (10–9 metre) in diameter. They resemble rough layered spheres with tiny arms extending from the top layer, each ending in a specially designed grapple. The spheres are tiny enough to remain suspended in liquid for several months. For tests, this liquid is mixed with a sample where the probes’ grapples will only plug into their predefined target cells, ignoring anything else.

Drs. Benoit Simard and Arnold Kell, who call themselves “architects at the molecular level,” are working with NRC biologist Dr. Jamshid Tanha to build minute probes that can quickly capture, manipulate and identify cells. The team is focusing on a rogue’s gallery of “bad bugs” — pathogenic bacteria — such as Salmonella, a food-borne pathogen, and Staphylococcus aureus, the germ behind hospital superbugs.

“Ideally, the more dangerous something is, the more quickly you want to identify it before incredibly bad things happen,” says Dr. Kell. “Better, faster diagnostics can improve both the health care and food safety of all Canadians.”

Before NRC researchers started building “nanoprobes,” medical doctors, fluid engineers, chemists, physicists and microbiologists had to painstakingly learn each other’s specialized concepts and vocabularies, and piece together common scientific ground and a language they could all work with. “Understanding each other took two years,” Dr. Simard says wryly.

Since then, he and Dr. Kell have led different teams to build specialized nanoparticles of two distinct sorts. One type extracts and separates specific types of cells; the other images and contrasts cells, giving labs multiple ways to identify them. They‘re now combining both types into more complex and multi-purpose nanoprobes.

Current lab techniques for identifying suspected pathogens involve culturing bacteria samples for up to two days to grow colonies that are big enough to identify. By contrast, the NRC nanoprobes simplify tests and accurately identify a few dozen pathogens within a couple of hours.

The probes include magnets so tiny they normally can’t attract each other. In what Dr. Simard calls “a beauty of nature,” their size prevents them from behaving magnetically, except near larger outside magnetic fields. This allows probes to drift freely in liquid to collect their target microbes, without affecting each other. Yet lab technicians can easily manipulate them later — magnetizing the probes simply by pressing a magnet to the side of the sample jar, to attract, concentrate and clump the pathogen cells in one place for easy testing.

Schematic representation of how nanoparticles can be used to interact with or "label" the surface of dangerous bacteria. If bacteria are effectively labelled with nanoparticles, they become "magnetized," which allows their efficient confinement with a simple magnet.

Other probes confirm whether a bad bug is present by fluorescing — i.e. emitting certain wavelengths of light — following irradiation. Dr. Kell says lab technicians can identify pathogen cells by testing the same probe with X-rays, CT scans, positron emission tomography, surface enhanced raman spectroscopy and/or magnetic resonance imaging.

The NRC researchers have also designed nanoprobes that target small, unique segments snipped from the DNA chains of some pathogens, potentially allowing epidemiologists to identify about 90 types of bacteria that they regard as most critical. They foresee their nanoprobes eventually forming the basis for small easy-to-use pathogen detectors.

“Our dream is to make them as simple as possible — and fast,” says Dr. Simard. “It would be realistic to imagine a gizmo just like the glucose tester that a diabetic person uses.”

Enquiries: Media relations
National Research Council of Canada

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