He openly admits that he aims to challenge conventional thinking with “crazy ideas”, and the science behind his work has generated a lot of discussion – and numerous prizes. One important aspect of his work is combining chemistry with 3D printing. We spoke with Cronin to find out how this could impact drug development.
What inspired you to combine chemistry and 3D printing? My focus is on complex chemical systems, and coming up with technologies or utilizing technologies that allow me to control complexity, or to at least monitor it. Big science questions can be enabled by developments in technology – and basically I see 3D printers as a ubiquitous cheap robotic that could be useful for exploring chemistry. I first got the idea of using 3D printing in my work about five years ago when I went to an architecture conference and I saw some people 3D printing ping-pong balls and plastic objects. It was really interesting, but plastic is quite limited so I wondered if I could do some sort of chemistry inside the ping-pong ball. That got me thinking about how I could print different compartments and then put different chemicals inside them – the idea for reactionware was born. I came up with the idea of reactionware after realizing that the 3D printer could not only print the test tube for the reaction, but could also be used to modify the test tube architecture and even include catalysts and separators (1, 2). In one of our first publications we even used the 3D printer, not only to fabricate the reactor, but also as a liquid handling robot – initiating the chemical reactions by adding the reagents directly into the reactionware.
What is the main goal of your research group? Our goal is to understand how life was created and to discover if we can make inorganic life. Some people think this is impossible, but life came from somewhere and the starting point must have been ‘inorganic’. Doing chemistry in the traditional wet-lab requires many types of manual operations from preparing starting materials to mixing reagents and initiating reactions. It is possible to automate it, but those automation control systems are extremely inflexible. Given our grand aim, to explore the systems chemistry at the onset of biology, we have been developing a series of automated chemical platforms that together could form a massively parallel chemical engine. We want to see how control of the architecture and control of the process allows us to merge lifelike molecules and systems. One potential technological spin off of what we’re trying to do could be in the area of discovery, from complex materials to drugs. I’m looking at how to make artificial life from the bottom up, but we could use the same system to program new discovery agents for drugs from the top down.
You’ve also been looking at printing medicines… We are developing a hybrid liquid-handling robot and 3D printer system to synthesize simple molecules, and so far it works with one very simple, commercially available drug. We both 3D print the ‘test-tube’ and use the 3D printer to add the liquids into the printed reaction chamber as a liquid handling robot. It was difficult to get it working, but we did it and we get a reasonable yield of pure material. We hope to publish details soon. There’s a lot of hype in this area, but do people really understand the technology? 3D printing is basically taking a hot plastic filament, screwing it through a nozzle and moving the X, Y and Z axis. But when you start talking about drugs and medicines some people misunderstand. You cannot print a molecule. In my group, we’re not printing molecules; we’re using a 3D printer to automate the synthesis of the molecule. 3D printing gives you the ability to control the X, Y and Z axes (length, width and height) to perform precise chemical operations. Aprecia Pharmaceuticals’ recent announcement has caused a bit of a media frenzy. Personally, I wouldn’t call it 3D printing of a drug exactly. They have automated the dosing of a solid form so that they can personalize the dose, which will improve outcomes for patients. It’s brilliant and they should be applauded for it. It’s not exactly a ‘3D printed drug’ as such, but it’s great to see pharma manufacturers getting involved in using this technology.
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References
- Mark Symes et al., “Integrated 3D Printed Reactionware for Chemical Synthesis And Analysis,” Nat Chem., 4(5), 349-354 (2012). Philip Kitson et al., “3D Printed High-Throughput Hydrothermal Reactionware For Discovery, Optimization, and Scale-Up,” Angew. Chem. Int. Ed. Engl., doi: 10.1002/anie.201402654 (2014).
