Q+A with Cell Biologist and Gibco CTS Rotea Collaborator Rebecca Lim

 

 

The story of the CTS Rotea Counterflow Centrifugation System for cell therapy and how innovation in science benefits from industry-academic collaborations

In 2017, Dr. Rebecca Lim had a chance encounter with David James, long-time entrepreneur-engineer and CEO of clinical technology startup Scinogy, on a bullet train to a meeting for the Australian Trade Commission. At the time, Lim was an academic cell biologist in regenerative medicine and cell therapy manufacturing. James and Scinogy had just begun developing a new benchtop device for cell processing in cell therapies and beyond.

Their meeting led to a lasting collaboration testing James’ prototype in Lim’s real-life wet lab setting. The rest is history. In less than three years, an industry-disrupting automated device for cell therapy research and manufacturing was launched to market on the global stage.

The Gibco CTS Rotea Counterflow Centrifugation System is a first-of-its-kind GMP closed-system, automated system for cell processing –washing, separation, concentration, and more– in applications like CAR-T therapy, stem cell therapy, and red blood cell isolation. It’s been a gamechanger for the scaled manufacturing of personalized cell therapy treatments, a field that has been challenged with bottlenecks in availability due to longtime technology barriers.

Lim, James, and her former doctoral student Anqi Li told the story of the CTS Rotea system’s path from infancy to meteoric launch and the key role of collaboration between academia and industry in a Reader’s Choice Gene Therapy review in 2021.

By collaborating with Thermo Fisher Scientific to bring the CTS Rotea system to global market, the team was able to explore the system’s capabilities with real cells, optimize parameters, and ultimately get more than 350 systems into the hands of researchers, manufacturers, and CDMOs worldwide.

We sat down to chat with Lim about what a fruitful academia-industry partnership can look like, how to set yourself up for collaboration opportunities, and the role of risk-taking in innovation.

 

Q+A with Dr. Rebecca Lim

Tell us a bit about your background. What motivated you to join the cancer research and cell therapy space?

I actually got my start as a stem cell biologist.  When I was applying for PhD scholarships back in 2002, I was going in completely different directions trying to figure out what I wanted to study. I got offers from three programs, and I had to make a choice. There was one opportunity with developing novel anti-virals for HIV infection and another with developing new plant-based medicines for MRSA – both important projects.

But then I saw an opportunity to study the role that adult stem cells could play in the development of liver cancer. In 2002, adult stem cells and cancer stem cells had a lot of ‘hype’ in the field. I asked myself, is it a trend? Will this topic actually have long-term roots in the scientific community?

I’ve always had a fascination with cancer research. I don’t think there’s anyone on Earth who hasn’t been touched by cancer one way or another. Everyone knows someone who has been affected by cancer, so I think it’s a disease that affects us all on some level. As we move towards longer lifespans, there will be increasing potential to accumulate genetic aberrations and we will be more susceptible to developing cancer at some point in our lives. Cancer research is an area that is going to require a lot of effort, and I’m very grateful to be part of the community in that effort.

And the liver cancer project was the one I went with. Throughout my scientific journey to date, I started through stem cell biology and regenerative medicine and have kind of gone back full circle to cancer research.

What was your role in the early development of the device that is now the CTS Rotea Counterflow Centrifugation System?

I helped with testing and developing some protocols using the technology. Anqi was really the hands and brains behind the technical operations of the Rotea in my lab. During the early development stage, we tested a number of different protocols using commonplace cell types such as PBMCs and MSCs to understand how varying centrifugal speed and flow rate could influence the rate of cell recovery. This is when we began to understand the extent to which common additives such as DMSO could influence media density. Our findings then allowed David and his team to adjust the protocol settings to account for those steps. From the software development side of things, we were able to provide feedback for his time to fine-tune the user interface in a manner that would be intuitive and flexible.

From your Nature review, it sounds like your involvement in this project had an interesting start. How did you meet David James, one of the Rotea system’s co-developers?  

I met David at a 2017 trade mission in Japan, which is a type of conference that governments organize to facilitate international relationship-building in scientific innovation and industry.

We were both there to discuss technology and to network, but funnily enough, we first connected between meetings over a common interest in dogs. We’re both enthusiastic about canine behavior and non-aversive training approaches, so every time we saw each other at lunch or coffee, we’d just circle back to that topic and ‘geek out’ about dogs. We’d take a deep dive and ask each other, “What have you tried? What do you think about this [training] method?”

The format of a trade mission is essentially like a road trip. You travel by bus somewhere to deliver your presentation, then get back on the bus, go to the next event, do the same spiel and repeat. So by the end of the first portion of the mission, we’d heard each other’s presentations maybe three or four times. And because we’d already connected over dog training, I think we each paid extra attention to the other’s talks. You know, you become extra invested because it’s like watching a friend at a gig.

 

Tell me more about the chance brainstorming session between you and David on the Nozomi Shinkansen bullet train line, and how it sparked a significant collaboration.

The trade mission eventually had us all travelling to events between Yokohama and Osaka, about an hour trip by high-speed bullet train.

So one day on the bullet train, I felt this tap on the shoulder. It was David leaning over from the seat behind me saying, “hey, take a look at this, I think you’d like it.” He showed me the Rotea system’s early rotary coupling and conical cell chamber – and he’s trying to explain the mechanism to me while leaning over the back of my seat and probably annoying my poor seat partner!

But that was our first conversation about the Rotea system. After that interaction, we started to talk more about the device and what he’d been able to do so far with the prototype. He showed me some more data, and we agreed that when he was in Melbourne, we would test it out in my wet lab.

 

What was it about this device’s approach that really grabbed your attention on the train and piqued your interest in collaborating?

At the time, my lab was involved in Phase I clinical trials with extremely premature infants to assess the safety and tolerability of allogeneic amniotic epithelial cells for bronchopulmonary dysplasia – a chronic lung disease of infancy.

We were working with unexpanded amniotic epithelial cells. In some of our trials, we were actually working with extremely premature infants who weighed only around 500 or 600 grams at birth (just over a pound, or the weight of a loaf of bread). I think the heaviest infant enrolled in our trial at the time was born at maybe 800 grams.

Cell therapy doses for these patients are very small. Before the Rotea came into the market, there was no small-scale piece of equipment for cell processing or buffer exchange. There was nothing that could fit inside our biological safety cabinets and work with small enough volumes.

To create an allogeneic cell therapy, you need to remove everything but the white blood cells. It’s a technically challenging task, and we had no option but to do it manually.

When David showed me the chamber on the train and explained how counterflow centrifugation could work –  that testing revealed that the system could precisely separate beads based on sedimentation properties like size and density – it clicked how much we could do with this technology with live cells. And the device chamber was only 10 mL volume. Could we then dispense an output even smaller than that? 5 mL?

We started playing with all these ideas with the initial consumable prototype. Things like – how many bubble traps are needed for the most common workflows? Where do the sensors go? How accurate is the optical density sensor in pushing subsequent cells through? We tested the device with leukopak prep, played around with buffer exchanges, everything we could think of. It was super fun.

 

Your Nature perspective piece centers the role of serendipity in this process – from conference brainstorming to a chance meeting on a bullet train in Japan.  But there’s also a nod to the Seneca quote, “Luck is what happens when preparation meets opportunity.” Are there ways that scientists – academics and industry-members alike – can proactively create the ideal conditions for collaborative innovation?

One traditional method of collaboration has the academic scientist testing a product in its final stages, after it’s been fully built, to collect validation data. It’s often not very fulfilling for the academic because the relationship doesn’t get formed, and you may not feel as personally invested in the technology.

I think the most fruitful collaborations happen in the prototype stage. The fact that I was able to contribute so early on with this technology’s development – when it was just a collection of machine parts built in someone’s garage – is really cool. Academics would sooner do that any day of the week than any late-stage collaborations, simply because they get to be part of the discovery process. How does it work? What does it take for it to work optimally? What can ‘break’ the software or the hardware? What redundancies need to be put in place to prevent operational failure? These are the fun questions that academics like to answer!

I think it’s good for innovators to be open-minded about collaboration and I’d urge them to consider the value of early stage collaboration.

What are your thoughts on the role of risk and failure in all of this, the innovation process?

Like I said, go into it with an open mind. But also go in with the expectation that nine times out of ten, something will fail. The real question is, are you enthusiastic enough in this collaboration to see it to its success?

It’s the Stockdale paradox – you need to have enough optimism to know that you will eventually succeed, but enough pragmatism to know that it’s going to be a slog. Don’t expect miracles. I think if you can take that kind of approach, you’ll have a lot of fun, you’ll meet a lot of people and build amazing networks, and yes, you’ll have an impact.

 

One of the other key collaborators on the early Rotea team was a jointly-funded PhD candidate in your lab, Anqi Li. How did her doctoral research contributions make an impact here?

Anqi came to me just as I was heading off to Japan and told me that she’d really like to collaborate on a PhD project that was industry-focused. At that stage, I believe she had been a researcher in the department labs for about 8 years and wanted to take the next step towards exploring industry. I had already worked with her and developed trust in her work, so I introduced her to David and his team.

Anqi joined us and provided great user feedback. Things like what the user interface should look like, where the buttons might be placed, what kind of tactile feedback should be kept – like a clicking sound when you place the cartridge kit in, which reassures the user that the kit is correctly in place.

Supervising her was simple because it is a productive collaboration when you have a candidate who knows what they want out of the PhD, and supervisors who are focused on the project and in growing the person along a very clear route that the student themselves has already identified. She took every opportunity to network with collaborators and did the wet runs for testing. She showed a lot of pride in being able to showcase the final product that was part of her PhD work.

 

What’s next for you?

In January 2021, I moved across to biotech where I have continued to grow my knowledge and expertise in cell and gene therapies. You could say that my experience with this collaboration was the spark that lit the tinderbox. I now work with academics on early stage technology development as an industry collaborator, and I continue to look for opportunities while continually preparing myself and those whom I have the pleasure of mentoring.

 

Learn more about the CTS Rotea system and cell therapy manufacturing at thermofisher.com/rotea » 

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Further Reading on Cell Therapy Manufacturing

• Cell Therapy Manufacturing: Protocol Handbooks, Virtual Lab, and more (Thermo Fisher Scientific)
• The Gibco™ CTS™ Rotea™ system story—a case study of industry-academia collaboration (Li, James & Lim 2021; Nature Gene Therapy)  
• Connect to Science Profile: Building the CTS Xenon Electroporation System
• Connect to Science Profile: What is CAR-NK therapy, and is it the “off-the-shelf” solution the cancer research field needs?
• Learn more about a day in the life of a leukemia research lab with Dr. Laura Eadie (Thermo Fisher Scientific)
• EBook: Counterflow Centrifugation (Thermo Fisher Scientific)

 

 

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About the CTS Rotea System

The multipurpose Gibco CTS Rotea Counterflow Centrifugation System applies the proven counterflow centrifugation method to a broad range of cell processing applications by customers including but not limited to T-cell processing (for CAR-T therapy), NK cell processing (for NK therapy), iPSC and MSC processing, and PBMC separation from leukopaks.

 

For Research Use or Manufacturing of Cell, Gene, or Tissue- Based Products. CAUTION: Not intended for direct administration into humans or animals.