Researchers at McMaster use 3D printer to create tool in hunt for new antibiotics
Specialized hardware for fight against bacteria was developed in-house
IF YOU CAN’T find it, make it. That’s what a group of McMaster University researchers have done with a specialized hardware that will be “game-changing” in their quest to discover new antibiotics.
The new lab instrument — a small, black box called the printed fluorescence imaging box (PFIbox) — was created in-house using a 3D printer at a cost of about $200.
The research — led by Dr. Eric Brown, director of the Biomedical Discovery and Commercialization program, and Shawn French and Brittney Coutts of the department of biochemistry and biomedical sciences at McMaster — was recently published in the journal Cell Systems.
The Spectator spoke with Brown about the impact of the tool and the democratization of research. This interview has been edited.
Where did the idea to create the PFIbox come from?
The work in my lab is all about trying to think about new approaches to antibiotics. One of the things that we kind of struggle with, believe it or not, is the nuances — the fine details
about how existing antibiotics work. There’s still lots to be learned about that. What the bacteria responses are to an assault by any sort of antibiotic is really useful information when we’re thinking about how to come up with new approaches to antibiotics. We have this set of clones we’ll call them, in other words a number of different strains of bacteria — about 2,000 — that report on basically the gene expression throughout the entire organism. It’s an engineered set of bacterial strains that basically place the switch for genes in front of a fluorescent protein. We needed a way to quickly interrogate these 2,000 strains, and the idea was to put them on an array and read the response — the fluorescence that would come off these strains. There was no instrument to do this. I have this really talented guy in my lab, he’s a research associate — Shawn French — and he’s always building things. It was about three years ago I joked that I bought him for Christmas a 3D printer. He built this thing, and it’s really cool. It’s got an iPhone camera, a little mini computer chip that basically is a Wi-Fi device and sends the data to the computer for analysis, and then it has an array of LEDs below to excite the fluorescent proteins. What is unique about this tool? We have another really cool device, which is a commercial device — not something we built — that allows us to array bacteria on what’s called a microwell plate. It’s two-and-a-half inches by four inches or so. It allows us to array these fluorescent bacteria at a density of 6,000 or so in that very small space. So we could array the bacteria but we had no way to read the fluorescence without this device. So it’s totally game-changing and actually relatively simple to make. Any kid could make this in his garage now if he wanted to, so it really kind of democratizes the research to have all this available. It started out on a Styrofoam box — just basically like a little cooler that lab reagents might arrive in. That’s when we realized we needed a 3D printer to make something a little more special. The other cool thing about that, of course, is once you print one of these devices, you could print 15 more and then you would now have a whole bunch of these boxes. At about $200 a pop, that’s really pretty easy to swallow in terms of now having a very high-throughput multiplex system to collect all kinds of data on the response of bacteria to antibiotics. What does it mean for accessibility given that the hardware cost $200 to create and a kid could do it in a garage? This concept that we’re using is publicly available, it was actually created by a laboratory in Israel. There’s a bit of a limitation in terms of the arraying device, but you could array at lower density without having a super-fancy arraying device. So it does mean that this is technology that really anybody can use. And for that matter, they could look at the box and say this is great for this application, and maybe we modify it a little bit, and it’ll be even better for what we want to do, which might be slightly different. I’ve been at McMaster 20 years, and I’d say it’s really in the last five or so years that device instrument building and certainly 3D printing has come on. It’s really changing the way we do things. We’re not limited by what’s commercially available anymore. If it’s not there, we just build it. What kind of advancements does that allow for? Now we’re gearing up to test these clones literally under hundreds of conditions. So we now have this multiplex, we’ve printed out 16 of these boxes, we could print more if we wanted. So we now have an array of arrays if you like, and we’re really going high throughput now on testing bacteria under a wide variety of conditions, really to try to understand what their responses are to antibiotics, what their responses are to all sorts of environmental assaults. We’re hoping that this data set in addition will really change our understanding of say what’s the Achilles heel of bacteria and allow us to make better choices about what it is that we should be targeting in the physiology of these organisms to get the upper hand.