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Part Two: Reproducibility and Cell Culture Automation: To Be the Human or Not To Be?

In Part One, Dr. Henn talked with Dr. Alan Blanchard of Thrive Bioscience about automation of manual cell culture processes and how that can improve reproducibility.

Here, they discuss whether it is better to mimic the human technician or not. The transcript was edited for length and clarity.

 

AH: What’s been your biggest challenge so far in bringing automated cell culture to life?

AB: From a technology point of view, it is keeping everything inside the box. We’re not allowed to cheat and take the cells outside to do some operation which would be easier to do outside. The difficulty comes not because any one particular operation or feature is difficult or tricky to implement, it’s that you have to implement all of these operations in order to make the instrument truly walk-away functional.

I think this is a big reason why no one’s done it before; it is a daunting task to do everything inside one box. There are companies that have automated bits and pieces of it. It’s not that hard to put a microscope in an incubator and have a robot running plates under the microscope, but that’s only 10% of the problem. The other 90% is fluidics, sterility, and image analysis. Nobody has done it all.

I would say the biggest challenge that we took upon ourselves was to do the entire process, to make the instrument truly labor saving and reproducible for our customers.

Unlike a lot of companies out there that already have existing product lines, we started from a clean sheet of paper. We didn’t have any agenda to sell more microscopes, more pipettors or anything because we don’t sell those. Our only goal was to make an instrument that was actually useful to cell culturists, that would relieve them from doing this sort of tedious work and let them concentrate more on interesting scientific aspects of what they’re doing.

 

AH: How clean a sheet did you have at first? Did you start without pipettors since there are no fingers in there, or did you decide to reiterate the human hand in a way in order to accommodate existing manual equipment and technician-based protocols?

AB: We started from the premise of what do we want to accomplish, not mimicking how people do things. We have redesigned how pipettors work. We tried to understand the function very deeply. What was really necessary to accomplish the task of growing and maintaining cells in a reproducible way?

In the Age of the Internet, it is time that automation and computer intelligence be brought to bear on the life sciences.

When Lab A makes a discovery and Lab B wants to reproduce that discovery, Lab A will often send a technician out to Lab B to transfer that knowledge. With our instrument, your protocol is a computer program. You could email this protocol to someone in Lab B. They could run it on an identical instrument and get the same results without having to move people to transfer intangible knowledge.

This is an issue with the contract research or manufacturing organizations. Often, experiments aren’t done the same way between two different facilities with different staff. But if a CRO was automated, you could guarantee that what was done in Boston could be done the same way in a facility in San Francisco.         

 

AH: So what is the biggest impact you see automation having on the basic research lab?

AB: We are seeing institutions wanting to scale up by a factor of 10. So an institution that may have 25 technicians whose full time job it is to change media would have to have an army of 250 technicians. That’s just not feasible. They really need automation.

In a research lab, automation is most important. There you’re trying to understand the effects of different environments, reagents, temperatures, gases, or signaling molecules. You really need that analytical instrumentation when you’re trying to figure out the effects of these different environments, but it is not commonplace in labs. So we want to bring that instrumentation to the lab.

 

AH: I want to dwell on that point for a minute. It is at the research level where it’s easiest and cheapest to make changes to a process that’s eventually going to end up in a clinical setting. But is that really the place for automation?

AB: In the lab, it’s easy to come up with, say, a hundred different media conditions that you might want to check to improve the cells, but without automation, it’s extremely difficult and tedious to actually do that experiment.

It can be difficult just to see the effects of different media compositions when you have variability introduced by manual manipulation of the cells. The fact that the technician did cell passaging a few hours earlier or the cells were out of the incubator for ten minutes instead of seven minutes can change the results. So we see a very interesting application for automation in just doing the basic but very important work of systematically going through different media compositions and seeing their effect.

 

AH: Thank you, Dr. Blanchard for your time and your expertise. We look forward to seeing what you do in the future!

 

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