Continuous metabolic monitoring in cell and gene therapy research
Tia Harmon (left) is a Technical Product Sales Specialist in the cell and gene therapy (CGT) space at PHC Corporation of North America (PHCNA; IL, USA) with a background in cancer research.
In this interview, we spoke with Tia about the importance of metabolic monitoring in CGT research, how continuous monitoring can overcome the limitations of traditional monitoring methods and the capabilities of PHCNA’s Live Cell Metabolic Analyzer (LiCellMoTM).
What excites you about working in the CGT space?
Even though CGT has been around since the ’90s, it remains a growing area, and it has future implications for how doctors will treat diseases. It can help to slow or stop the progression of disease, which – of course – is exciting because that’s what we all want.
Why is metabolic monitoring important for CGT research?
Metabolite monitoring gives researchers an understanding of what is happening during cell metabolism. When cells become activated, a ligand binds to a receptor, which leads to a cascade of downstream events. These events could be cell proliferation or the release of cytokines, enzymes, inhibitors or molecules of that nature. Therefore, being able to pinpoint when these events are happening provides an insight into what the cells are doing metabolically and how that could be augmented for therapeutic purposes by adding an inhibitor or a drug, for example. Metabolite monitoring is important because it gives a full picture of what’s going on with the cell so researchers can address it from a more holistic standpoint.
What challenges exist when monitoring metabolites in cell culture?
The challenges that currently exist are in part due to the nature of traditional periodic sampling. Periodic sampling provides discrete endpoint metabolite measurements, which doesn’t capture the dynamic nature of cell metabolism and doesn’t offer real-time information about the cell culture. It also requires labeling; researchers must introduce reagents to look for specific markers. And finally, this monitoring method requires sampling, which is laborious and means researchers must be at the bench at certain times to manually sample culture media and input it into a specialized instrument their lab may not have readily available. Sampling can also be disruptive to the cells, introducing contaminants or causing cell loss.
What is LiCellMo, and how does it work?
LiCellMo is an instrument that measures glucose and lactate metabolism in real time. It has a few components, including a sensor module, detector and controller. The sensor module is the consumable, which sits on top of the culture plate, inserting an electrochemical sensor probe into each well of a 24-well plate. These probes are designed with glucose and lactate dehydrogenases that produce an electrochemical gradient readout every 15 minutes containing minute-by-minute data, which informs glucose consumption and lactate production, as well as metabolic rate. The 24-well plate assembly is then placed in the detector, which is about the size of a shoebox, making it possible to fit four of them in a standard-size incubator. The controller outside of the incubator allows researchers to monitor the metabolic data as it’s read out.
How does LiCellMo overcome the challenges associated with traditional metabolic monitoring?
LiCellMo addresses the challenges associated with periodic sampling methods by conducting continuous measurements, gleaning more information about cells’ metabolic profiles and giving researchers a fuller picture of their cell cultures without having to sample the culture media. The cells are free to grow, undisturbed, in the incubator, which means there is less chance of accidentally contaminating the cells or causing cell loss. This technology is also label free, so it doesn’t require the addition of any reagents or dyes to look for specific markers. This way, the cells can be preserved if they are needed for downstream assays. Its small size means it has a small footprint; you simply place the detector inside your incubator, and you don’t have to create extra space in the lab. Finally, LiCellMo is an intuitive instrument that doesn’t require extensive training to use.
How are innovative tools – such as LiCellMo – propelling research forward?
Continuous monitoring is helpful in cancer research, especially when we think about treating with different drugs or inhibitors. Each well in the 24-well plate can contain different experimental conditions. We always want to have a blank well as our control, which contains untreated cells; however, to other wells, we can add activators or inhibitors. This can be done before placing the cells in the detector or at a later stage since there is the option to pause the system via the controller. Once you’ve paused it, you can remove the plate, and then add an inhibitor or drug to the particular wells of interest at that time point. This will allow the researcher to determine metabolic changes induced by the treatments.
Continuous monitoring is also beneficial for stem-cell research and manufacturing. If manufacturing iPSCs for reprogramming, for example, continuous monitoring provides clear guidance on when to change your culture media to produce more robust cells.
What advice would you give to lab managers when selecting new tools for CGT research?
Before purchasing any piece of equipment, I always say that you want to look for reliability and efficiency. PHC has been around for over 60 years; our legacy stems from Panasonic and Sanyo, so we have a name in the business. We have established a reputation of reliability.
From an efficiency perspective, you also want equipment that’s going to free up time for researchers to perform other important work. The LiCellMo is continuously monitoring in the incubator, and each sensor can be run for up to 10 days. This allows scientists to spend their time conducting other valuable research and simply allows them to be away from the lab during weekends.
Part of this efficiency point is asking: can the equipment be easily integrated into the lab?With LiCellMo, you can use standard 24-well plates, and our state-of-the-art incubators. It is also likely compatible with non-PHCbi brand incubators already in the lab.
To summarize, when selecting new tools for CGT research, you should consider reliability and efficiency, but you should also consider the value the equipment brings to your research and your lab staff.
Interested in learning more about continuous metabolite monitoring? Check out our In Focus on the topic!
The opinions expressed in this interview are those of the interviewees and do not necessarily reflect the views of BioTechniques or Taylor & Francis Group.
LiCellMo is available for purchase in the U.S., Canada, and select other geographies globally. For research and education use only, not for use in diagnostic procedures in the U.S. or Canada. This product has not been approved or cleared as a medical device by the U.S. Food and Drug Administration or Health Canada.
This interview is sponsored by PHC Corporation of North America.
