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EPFL tests antibiotic resistance with simple optical platform

26 Apr 2023

Conventional optics and smartphone camera could make health testing cheaper and faster.

Assessing how resistant different bacteria are to antibiotic treatments is a vital current challenge in public healthcare, as instances of antibiotic resistance continue to grow.

Optical techniques have played a part in making these assessments more convenient for clinics, as in the lensless imaging system developed last year at CEA LETI which recorded the characteristic light scattering of different bacteria as a means to identifying them as rapidly as possible.

A project at Switzerland's EPFL research center and Vrije Universiteit Brussel has now developed a simple platform designed to test antibiotic susceptibility, combining simple optical microscopy with a basic camera such as those in smartphones. The work was published in PNAS.

The simplicity of the apparatus should allow clinics to carry out faster testing without the expense and complexity of existing and slower methods.

"We have developed a technique in our laboratories that allows us to obtain an antibiogram within 2 to 4 hours, instead of the current 24 hours for the most common germs and one month for tuberculosis," commented Sandor Kasas from EPFL.

The device exploits the fact that all living cells oscillate at a nanometric scale, a finding that the researchers had previously suggested could be used to monitor whether cells were alive or dead in extreme testing scenarios or demanding environments such as space exploration.

Measuring cellular motion in that project required the use of microfabricated cantilevers, placed in contact with the cells of interest. Nano-oscillation of the cells created corresponding movements of the cantilever, monitored through the deflection of the laser beam of a commercial atomic force microscope.

A game-changer for developing countries

Although the new device employs the same principle, it makes use of a considerably simplified system based on a traditional optical microscope. In 2020, while studying the nanomotion of yeast cells, the project had determined that the movements could be analyzed in a straightforward manner by recording multiple video frames and applying optical nanomotion detection (ONMD) algorithms to the data.

That study had included exposing the yeast cells to killing agents, and recording their effects by studying the changes in nanomotion. The same principle has now been applied to assessing the response of bacteria to antiobiotic treatments, using a homemade analysis chamber with a traditional optical microscope and a video camera or mobile phone.

"Cellular displacements were measured by tracking every single cell with a subpixel resolution, or by highlighting in false colors the regions of the field of view that changed the most between consecutive frames," noted the project in its PNAS paper.

In trials, the team's ONMD software successfully detected the sensitivity of bacteria including Escherichia coli and Staphylococcus aureus to the antibiotics ampicillin, streptomycin, doxycycline, and vancomycin. A determination of the antibiotic effect could be made in less than two hours, much faster than with traditional methods according to the project.

As well as monitoring the life-death transitions when exposed to different antibiotics, the new method can also highlight changes in the bacteria's metabolism caused by the availability of nutrients, and makes these determinations independently of the bacterial replication rate or motility.

"The technique's simplicity and efficiency opens novel avenues to fast antimicrobial testing, specifically in developing countries, and make it a game-changer in the field," noted the project

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