See how they grow: Monitoring single bacteria without a microscope

With an invention that can be made from some of the same parts used in CD players, U-M researchers have developed a way to measure the growth and drug susceptibility of individual bacterial cells without the use of a microscope.

The new biosensor promises to speed treatment of bacterial infections, says Raoul Kopelman, who is the Richard Smalley Distinguished University Professor of Chemistry, Physics and Applied Physics and a professor of biomedical engineering, biophysics and chemical biology.

Instead of waiting days for culture results, clinicians will be able to determine in minutes the antibiotic best able to treat the infection. This advance, along with the sensor’s potential use in screening existing and newly discovered compounds for antibiotic activity, could improve patient outcome, reduce healthcare costs and reduce the spread of antibiotic resistance.

Because it also detects the response of individual cancer cells, the sensor could someday be used as well in cancer drug development and treatment. The research is reported in the Jan. 15 issue of the journal Biosensors and Bioelectronics.

The device, called an asynchronous magnetic bead rotation (AMBR) sensor, was invented in Kopelman’s lab at U-M. Early development of the sensor, also in the Kopelman lab, was primarily the work of Brandon McNaughton, who was a graduate student at the time. McNaughton went on to found the U-M spinoff Life Magnetics Inc., where as chief technological officer he is further developing the device.

The AMBR sensor uses a spherical, magnetic bead that asynchronously spins in a magnetic field. Just as a pencil attached to a child’s toy top creates drag that affects the way the top spins, anything attached to the bead slows its rate of rotation. In the current work, the researchers attached individual, rod-shaped Escherichia coli bacteria to individual beads and watched what happened, using the newly developed AMBR sensor.

“The method can detect growth of as little as 80 nanometers, making it far more sensitive than even a powerful optical microscope, which has a resolution limit of about 250 nanometers,” says graduate student Paivo Kinnunen, one of the paper’s lead authors, who also is working at Life Magnetics while completing his studies. (While the AMBR sensor does not require a microscope, one was used in the current study to confirm results).

The U-M group demonstrated that the sensor not only can monitor the growth of a single bacterium throughout its life cycle and over multiple generations, but it also can determine when an individual bacterium stops growing, in response to treatment with an antibacterial drug, for instance.

“You can basically tell, within minutes, whether or not the antibiotic is working,” Kinnunen says.

In the near future, “we expect it will be possible to make the determination even quicker,” says graduate student Irene Sinn, the paper’s other lead author.

The device also can be used for monitoring the growth and drug susceptibility of other types of cells, Kinnunen says.

The technology could have far-reaching implications, McNaughton says.

In addition to Kopelman, Kinnunen, Sinn and McNaughton, the paper’s authors are Duane Newton, associate professor of pathology and director of the microbiology/virology laboratory, and Mark Burns, professor and chair of chemical engineering.

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