Founded in 2018, British biotechnology firm YouSeq designs, develops, and manufactures easy-to-use Next Generation DNA Sequencing (NGS) kits, panels, and reagents.
We spoke with Senior Scientist Tom Huckvale about how YouSeq uses three Opentrons OT-2 robots for developing custom gene panels and for purifying DNA using magnetic beads.
Tom Huckvale in the YouSeq lab with one of his OT-2 liquid handling robots. CREDIT: Tom Huckvale
Opentrons: What specifically do you use the OT robots to do, and how do they fit into your workflows?
Tom Huckvale: The first thing they’re used for is taking primers. We have primer pairs for our NGS panels that arrive in 96-well plates from the manufacturer. We have to pool specific volumes from specific wells from specific plates to individual tubes—so individual pools of primers that we then use for our NGS kits.
Sometimes we want to pool equal volumes of every single [primer] into one tube. Increasingly, we do much more varied protocols. We could easily have tens of thousands of primers and want to put different volumes of each primer from a hundred odd plates into individual tubes for our reactions. We might not want to take everything from one plate: we might only take a few from one, a few from another. So that’s how the Opentrons robot fits in.
The beauty of these robots, with the open source nature of them, is we have big databases of all of our primers, all of our primer pairs, how they performed, and the QC that’s been done on them. All of this fits into creating spreadsheets that the robot can read.
The beauty of these robots, with the open source nature of them, is we have big databases of all of our primers, all of our primer pairs, how they performed, and the QC that’s been done on them. All of this fits into creating spreadsheets that the robot can read. With a lot of manufacturers, you’re pretty locked into how their software handles things. There are a lot of proprietary file formats. But we simply give [the robots] CSV files with volumes, well IDs, where it’s got to go, it translates them perfectly, and then just runs.
We also have another Opentrons robot with a Magnetic Module in a separate room for doing DNA purification with magnetic beads. A lot of our experiments involve plates of reactions, and cleaning these with the magnetic beads by hand is a little tricky. From scratch, over a week, me and my colleague Daniel came up with the ultimate bead cleanup method for this robot. It does it really, really nicely every time, so we can give it a whole 96-well plate of DNA to clean, and it’s just going to do that in the background.
I mean, to be fair, we kind of do it by hand, but we’re experienced with doing lots of bead cleanups, so we’re quite quick anyway. It’s not a time saving on that. But simply being able to set something off and then to use that time to write up experiments, come up with new ideas, do something else, has been quite critical. You can hand off these jobs to the robot and be pretty confident that it’s going to be largely as good as if you’d been sat there mindlessly pipetting.
Opentrons: I understand you’ve been writing protocol scripts in Python. How come you ended up going that route, as opposed to using Protocol Designer, where it’s more a pick and choose method?
Tom: We used to make protocols with the Opentrons Protocol Designer app. It’s a really low bar of entry into using the robots, and that worked really, really nicely. But that had some limitations, especially with the magnetic bead cleanup. You couldn’t write protocols using the magnetic module using the Protocol Designer.
So we looked into the Python scripts and realized that, actually, they’re very straightforward, especially using the Opentrons API on the website. And printing out—there’s a PDF—to have as a reference while you’re sat next to it. You can find anything you’d want to do in there. You need to spend some time getting it all set up, but really, once it’s up and running, it requires almost no input at all.
Opentrons: I was going to ask why you chose Opentrons over larger manufacturers, but I don’t know if you can answer that since the robots predate you as employees. [laughs]
Tom: [laughs] The market we’re in, there are some really big players. The barriers to entry are pretty high. You need a lot of upfront investment, and we have, you know, startup cash. It’s a case of what we can get with what we have to spend while keeping as much control over the company as we can. We need automation in order to compete with a lot of these companies on price and the quality of the product.
And [using Opentrons] means that we don’t need to subscribe to or learn new software just to write protocols for it. In previous jobs where automation was used, you’d need to learn new pieces of software that are specific for that particular robot from that manufacturer. Because it takes a couple of weeks, you’d have one person who learns how to do it, and then the robot can only be used by the one person.
We want to get everyone in the company writing scripts for these Opentrons robots. I mean, I’d like to see a bench with ten of them on, and everyone in the company at least at some point having some interaction with them, even if you’re just using a couple for fun or to try things out.
Opentrons: You’ve mentioned how having the robots has made you competitive with the larger, older companies. How do you think the business would be different if you hadn’t automated?
Tom: I think if we didn’t have this automated, we would be offering much less complex products and potentially only a few of them. And it would be difficult to take on new orders. Because of the open nature of it, we have this pipeline now integrated really nicely with the robots as soon as there’s custom orders, that really it’s very quick to have the robot within… I mean, okay, so we have to defrost some things, but saying everything’s defrosted, you can have an order come in, and you can be preparing the panel within half an hour, 20 minutes. If we were doing this by hand, we wouldn’t have that speed.
Tom working with his OT-2 robots in the YouSeq lab. CREDIT: Tom Huckvale
We would also be making mistakes, and that’s a real danger. We need something that is consistently good. If you can free it from — it sounds a bit sad, but — free it from human error, that does keep customers happy.
Opentrons: NGS is all about having that high throughput, faster, less expensively, and precisely, almost by definition. How has lab automation affected your own throughput and precision?
Tom: In terms of the R&D for these products, we can do more. If I were to design an experiment that I would have to do by hand, I would have fewer variables that I could test at any one time. With the robots you can finely tune a lot of these experiments. For example, in the primer pools, you can make adjustments to the volume and concentrations, individual assays, which you wouldn’t really be able to do by hand. It would take you a few days, and you would lose your mind.
With the robots… you can make adjustments to the volume and concentrations, individual assays, which you wouldn’t really be able to do by hand. It would take you a few days, and you would lose your mind. But you can get robots to do this in an afternoon.
But you can get robots to do this in an afternoon. It means you can get to better products faster. You can optimize a lot of your processes. You can get to answers faster. You can try more things, which means you can get to the quality of product you like and in fewer steps.
All in all, it’s made a big difference. It’s certainly something I’d recommend to anyone. We have customers that want to get into NGS, so they come to us, and we design them panels. But also we’re suggesting that they look into Opentrons and getting the magnetic bead purification stuff done on the robots. We share scripts that we’ve written with them, so they start running them. Opentrons helps that. There’s no proprietary file format, no security. You don’t need special passwords. You just send them a text file that they can then get their robot to read, and the same thing happens 3000 miles away as in our lab.
Part of YouSeq’s philosophy is that NGS doesn’t have to be complicated at all. A lot of labs want to do NGS but see that it’s a lot of jargon, a lot of stuff doesn’t really make sense, it sounds really complicated, don’t you need huge amounts of data, don’t you need special tools… And we’re kind of saying that actually, no, it’s really simple, and we’ll show you how to do it. Opentrons fits into that philosophy as well. It’s nice to find companies that are thinking the same way. We have quite a big respect for Opentrons anyway with what they’re trying to do, and so we want to support that as well. It just so happens that their stuff works, and we love it.
This interview has been edited for length and clarity.