Q&A: Making a 30 minute test is our challenge

4 October 2017
Written by
Shannon Harmon
Silicon chips used in antibiotic susceptibility tests.

Heidi Leonard is PhD student in Professor Ester Segal’s lab at the Technion in Israel. Her team, Prismatix, is working on a multifaceted test to determine what bacteria is causing an infection and which antibiotics will be the most effective. Starting with urine samples, they plan to move towards testing other samples, like blood and sputum, for various infections. The biggest challenge, however, is making a rapid test that works within 30 minutes.

Electron microscope images of ball-shaped Staphylococcus (left) and oval-shaped Enterococcus (right) growing in different silicon microstructures.

What do you see as the biggest issues around antibiotic resistance and why?

Right now, the prolonged amount of time it takes in the hospital to determine antibiotic resistance in an infection is the biggest and most solvable issue regarding antibiotic resistance. The longer it takes for a patient to receive the correct antibiotic, the more likely they are to take an ineffective antibiotic that will increase the likelihood of spreading antibiotic resistance. Therefore we need a rapid diagnostic test to tell us which bacteria are present and respond to what antibiotic.

How will your test help tackle antibiotic resistance?

It significantly shortens the time needed to determine the correct antibiotic for an infected patient, therefore the patient will take the correct antibiotic as soon as possible.

What bacteria does your test target?

At the moment, it works best for identifying E. coli and other rod-shaped bacteria.

However, we are optimising the test to work with virtually every bacterial strain, especially those related to hospital-acquired infections and urinary tract infections.

What is the PRISM method?

We trap bacteria from a urine sample in patterned microstructures a couple of micrometers in size on small colorful silicon pieces - or chips. When bacteria grow and die on the chips, we can see changes in how the light reflects off the chips. If bacteria continue to grow after we add antibiotics on the chips, then we know we have resistant bacteria.

How does the Prismatix diagnostic test work?

In this video, Heidi explains the Prismatix diagnostic test in the lab at the Technion.

In what settings is your test expected to be used?

Thus far, our test would be optimal in a clinical lab setting. However, because it requires very little equipment, it has the possibility of transitioning to a non-hospital setting as well. We perform our tests in the lab, but someday it could be handheld. This is a goal, as we would like to apply for the Longitude Prize and being point-of-care is necessary for the application.

Your application said the Discovery Award funds would be used to make some disposable microfluidic devices. Can you describe this?

Originally, we performed all our assays in a bulky, inconvenient set-up. We have now transitioned to disposable microfluidic devices in which samples are easily injected.

These are small devices, about 3 x 1 inches, the size of a microscope slide. The devices contain small channels with chips in the center. They do not require a skilled person to use, but someone that can simply inject a sample.

Observing phenotypic resistance without significant sample handling in 30 minutes, however, will be the biggest challenge.

The devices have already been preloaded with antibiotics and simply need to be placed under our detector. The detector reads bacteria growth every couple of minutes and measures growth or death within the preloaded antibiotics.

It currently takes two hours to complete the test, but we hope to make it faster.

How will producing these devices help you develop your application for the Longitude Prize?

These devices will significantly reduce handling time by being able to take the samples and put them directly into the device, in addition to reducing the assay time getting us closer to the 30 minute mark required for the Longitude Prize application.

What do you see as the struggles you will face in the run up to applying for the main Longitude Prize?

Making our test point-of-care is not the biggest struggle for us, because we don’t use a lot of equipment or microscopes. Observing phenotypic resistance without significant sample handling in 30 minutes, however, will be the biggest challenge. It takes most bacteria at least 20 minutes to divide, which only leaves 10 minutes for a test result, which is not a lot of time. Effects of the antibiotics may take longer to observe and not all bacteria take the same amount of time to divide.

What are the next steps after you finalise the development of this test?

We are working towards antibiotic susceptibility testing of direct urine samples, but we plan to move towards testing other samples. Any sample ,hypothetically, could be used in our system, however we have not experimented with blood yet.

If you’re successful, who would manufacture your test and what would be your initial target market?

We are still determining the logistics of who would manufacture the test. It helps that Israel is an excellent place for start-up companies. Our initial target market would be Israeli medical labs, though there is no reason to limit the test to Israel.

Our Q&As are edited in partnership with the interviewee for brevity and clarity.