The Science Behind the Technology

Charlotte Bermingham is CTO at Vitamica, a newly incorporated University of Bristol spin-out. The company is based on work pioneered by CSO, Dr Massimo Antognozzi, at the University of Bristol and was set up together with Innova Partnerships. She joins Anna Fleming to discuss their innovative technology and its applications in the fight against antibiotic resistance.

Could you explain Vitamica’s technology? What does it do?

It’s basically a really fast way to determine whether bacteria are alive and if they are affected by antibiotics. The standard approach right now is to incubate them overnight and see if they grow and multiply, but this takes a long time – usually upwards of a day. Our technology is a simple optical technique that we use to image tiny fluctuations in the bacterial cell envelope, which only happen when that cell is alive. If the bacterium is living, you see lots of shimmering fluctuations, and if it’s dead, it looks still.

What applications might it have?

The main application is susceptibility testing. If you get an infection, a sample might be sent to a hospital, where they test it against different antibiotics to see what it’s resistant and susceptible to. At the moment, as I mentioned, it takes around a day to incubate the bacteria, and then you need another day for susceptibility testing. Ideally, you would want to do that before prescribing an antibiotic because otherwise, you might have a patient going home with an ineffective drug. On the other hand, if you wait for the results before prescribing you risk patients deteriorating dramatically over the two days it takes to run the tests.

Our technology could substantially reduce the time needed for testing because it doesn’t rely on bacterial growth to tell if the bacteria have survived a round of treatments.

How rapid is it? Would you say we’re heading towards being able to run susceptibility testing before a GP prescribes?

Ideally, yes. Right now we can do it in tens of minutes rather than tens of hours. We’re not sure exactly how fast it will eventually be because at this stage I’m doing everything manually. We want to automate which will speed it up.

 

Charlotte working in the lab at the University of Bristol

How does your approach differ from those of your competitors?

Growing bacteria over hours is the standard approach; the vast majority of susceptibility tests are done that way. It’s possible to automate the process, which takes it down to about a day, but you still have to culture the bacteria, which is slow. Even with a system detecting very early stage growth, you’re limited by the speed at which bacteria will grow. There are molecular mechanisms which detect fragments of DNA indicative of a certain resistance mechanism, but they’re most useful when looking for something specific. If you’re looking for MRSA you know what DNA to search for, whereas if you just want to know whether something’s resistant but you don’t know what mechanisms it’s using, you’re essentially going in blind.

Did you set out to fill this niche in the market or did the technology develop first and then an application become apparent?

The essence of the technology has been developed by Massimo Antognozzi’s lab over several years, albeit originally for a different purpose – to detect very sensitive mechanical sensors for force measurements. A few years ago, the Kasas group in Lausanne discovered that bacteria exhibit nanoscale fluctuations when alive, in experiments using very sensitive mechanical sensors.

We saw this paper and decided to repeat the experiments with more sensitive sensors. Then we realised because of the way the optics are set up in our system we could directly see the nanoscale fluctuations of individual bacteria, removing the need for mechanical sensors at all, making it a much simpler and more robust technique. We investigated the effect further and found we can monitor bacteria in real-time to determine whether they are alive and how they respond to various drugs or not.

Can you explain that in more detail? Roughly how does the system work?

We illuminate a sample of bacteria with low power laser light, such that only its lower surface is in the light field. The bacterium scatters the light and we image this scattered light on a high sensitivity camera. The key to our imaging method is that extremely small movements in the bacterium can be picked up because they affect the scattered light and cause intensity changes on the camera. So the shimmering we see is actually physical movement in the outer layers of the individual bacteria.

 

Preparing a sample for analysis

How did you get from there to where you are now?

We always had antimicrobial susceptibility in mind as a possible application, because it is such a big current problem and it sparked off us investigating the fluctuations as interdisciplinary research projects. Then we joined SetSquared’s ICURe scheme, which involved talking to potential users of our technology to find out where and how it could be applied, and to make contacts in relevant areas. After a few research grants, we won a prize from the Longitude Foundation to further develop the technology specifically for susceptibility testing, followed by an Innovate UK grant, which prompted us to set up the company, using Unit DX for our business base. It’s conveniently near the University, which makes for a smooth transition from the University labs to the “real world” such as the lab space at Unit DX. We also won funding from the BrisSynBio 4-Day MBA course at Unit DX, which has been very helpful in getting up and running.

What are your plans now – how you see the technology being used?

We want to see it being used in hospital laboratories for susceptibility testing – and we have a year to prove that this is feasible. During this time we will secure investment to build more prototypes and begin trials with clinical samples.

Vitamica are preparing to launch their website this week. In the meantime, please keep an eye on their twitter page.