Advantages and disadvantages of the automated cell counter

Automation is a major theme in the biopharmaceutical world, and the automated cell counter is an essential piece of equipment. As industry moves at lightning speed to implement automated tools, it may feel overwhelming to understand the draws of one particular instrument over another. Hardware is complicated and depends on software to work properly. Ultimately, the instrument has to fit in with your operations and systems for you to benefit.

Despite the necessity of an automated cell counter in many operations, there are important considerations that may hold you back from making the switch, for the time being.

We all know that manual processes are more error-prone and not suited for scalable manufacturing. But making the investment in one or multiple automated cell counters is not a simple decision.

How does an automated cell counter work?

Automated cell counters work in different ways, meaning that there are unique advantages and disadvantages to each type of instrument and model. Generally speaking, however, there are some clear pros and cons that apply to all of the products, and that is what we will cover in this article.

How many types of automated cell counters are out there?

There are many types of automated cell counters. Some automated cell counters take images of cells, either using staining techniques or being label-free, and then apply sophisticated algorithms to enumerate the cell population from the captured image.

Flow cytometers, on the other hand, use laser beams to analyze cells based on their size, shape and fluorescence properties. The third type of automated cell counter is the electrical impedance-based cell counter, which measures changes in electrical conductivity as cells pass through a narrow channel.

For a general overview of cell counters, refer to our Ultimate Guide to Cell Counters article.

Automation ≠ standardization

The hemocytometer allowed scientists to enumerate cell populations for the first time, a task with a wide range of applications in the life sciences and the food industry. However, for some cell-based processes, an automated cell counter is required for compliance reasons, such as for manufacturing biologics and cell therapies, or in single-cell sequencing.

At the same time, there is no standardized method to count cells. This means we cannot know exactly how many cells are in a sample with 100% certainty. Cell counters from different manufacturers will all count differently. Inter-instrument comparisons are therefore not so straightforward.

For this reason, the hemocytometer still plays an important role in cell counting. All automated cell counters on the market are typically compared to and validated against the hemocytometer, typically by performing a dilution series. Despite how old the technology is, the specialized slide is still used as a barometer to judge the performance of new, sophisticated cell counting technologies.

Let’s now review common advantages of automated cell counters.

What are the advantages of an automated cell counter?

Speed and efficiency

One of the most significant advantages of automated cell counters is how quickly they can count cells. Because cell counters work quicker than a human counting cells by hand, the entire workflow the instrument is a part of becomes more efficient. Resources can be freed up due to not needing to physically manage every step of the cell counting process.

The automated cell counter can enumerate thousands of cells within seconds, an impossible feat to match with manual cell counting. This benefit is advantageous when aiming to reduce time-to-market and prevents cell counting from ever being a bottleneck in your operations.

Increased precision

Understanding cell count is absolutely vital for the entire biopharmaceutical industry. Precision, defined as the closeness of repeat measurements to each other, is required to obtain a clear understanding of any cell-based process. If one cell counter varies by 20%, and another by 5%, the latter is going to pave a clear path forward to reaching your goals, whereas the former may increase the chance of costly mistakes and even result in manufacturing failures.

The automated cell counter is generally—depending on the instrument—a lot more precise than manual cell counting. The exception would be if we compare a machine with high cell counting variation to a human operator with excellent pipetting technique using a hemocytometer.

In this case, it could be possible for the manual cell counting method to outperform the poorly performing automated cell counter. It is thus important to consider the coefficient of variation in a sample of measurements and compare this with similar products on the market. You can ask a field application scientist to help you run this experiment during a live demo.

By counting more cells, the precision of the measurement increases and the results are more reliable. Automated cell counters also increase the precision of the count by minimizing human error, a common source of variability in cell counting.

Counts many cell types

Using the NucleoCounter® line of cell counters, only one protocol is required for the vast majority of cell types. Whether neurons, liver cells or iPSCs need counting, we have ensured that only one protocol is required to accurately and precisely enumerate most cells.

This is important because not all cells are created equal.

However the cell counting method should ideally not need adjusting in order to work. This improves ease of use and efficiency.

To the contrary, having specific protocols for specific cell types could make sense, if accuracy could be increased. But differences in the algorithm may insert bias into the system and lower objectivity of the result.

Either way, automated cell counters are designed to be able to handle a wide variety of cell types and may even help identify cellular debris or non-cellular material in your sample. With some cell samples, it is not possible to obtain suspension cells, and thus you may benefit from a cell counter with this capability.

Data analysis

Many automated cell counters come equipped with integrated data analysis software. This goes beyond providing measurements of total cell count, cell viability, cell concentration and live/dead cell count. Most automated cell counters allow you to see your data to gain a deeper understanding of how cells were analyzed by the software’s algorithms.

By doing so, the automated cell counter aids in the interpretation of results and facilitates data-driven decision-making.

Healthier cells

With a fast processing time, cells avoid staying in suspension and stains, such as trypan blue, for too long. When cell counting becomes a bottleneck, cell health may deteriorate depending on the stains and media used.

Diluents such as phosphate-buffered saline lower cell viability by 25% after just five minutes of incubation. By using an automated cell counter with not only a low processing time, but also one that is so easy to use that cells never have to wait in solution before counting, you will analyze healthier cells and receive a more accurate cell count.

Pros and cons of automated cell counting

This advantage however may not apply to high throughput automated cell counters. In these types of products, the user can load multiple cell samples into a tray and wait for the cell counter to provide the results, instead of loading each sample one at a time. This is called walk-away cell counting, because you can walk away and focus on other tasks as the instrument analyzes all the samples.

What could happen here is that different samples spend different amounts of time waiting. It is not unusual to see a progressive drop in cell viability as the samples get counted. If you are considering a high throughput cell counter, ensure to double-check that cell counts are not significantly different between samples (sometimes referred to as “positional bias”).

Compliance-ready software

To comply with 21 CFR Part 11, many automated cell counters include special data handling software, including features such as an audit trail and restricted user groups. Learn more about these advanced features in our article here.

Reduced fatigue

Manual cell counting can be labor-intensive and lead to operator fatigue. Automated cell counters allow staff to focus on the data analysis and interpretation rather than perform busy lab work.

Disadvantages of Automated Cell Counters

Cost

Automated cell counters can be expensive to purchase, use and maintain. The initial investment includes the price of the equipment, but ongoing expenses may come from consumables, reagents and maintenance. This cost can be a significant barrier for smaller research labs, startups and healthcare facilities with limited budgets.

While determining if an automated cell counter fits your budget, evaluate the long-term cost of the instrument. Even if a significant investment is required, the benefits may outweigh the costs in the long run. This is especially true if your processes improve as a result, allowing you to decrease costs elsewhere or produce a better product.

Operator training

While automated cell counters are user-friendly, operators still require proper training to use them effectively. Inexperienced users may struggle to set up the equipment, perform routine maintenance or troubleshoot technical issues. Worse, without proper training carried out by the manufacturer of the instrument, misuse of the instrument may occur, undermining the integrity of the data. It is thus vital for GMP personnel to receive regular training, as is encouraged by both US and EU authorities.

For GMP processes, regular training of staff is required by regulatory authorities in both the United States and the European Union. Investing in an automated cell counter is a continuous long-term decision. Integrating new analytical tools into your processes requires harmonizing operators across departments and sites.

Lack of automation

Wait a minute… aren’t automated cell counters all automated? Yes, but not fully!

Many automated cell counters will require manual sample preparation steps, such as carefully pipetting a precise volume of sample onto a cell counting slide or manually staining the sample. A fully automated cell counter will integrate with pipetting robots and require no manual operation steps.

Despite the benefits of full automation, not all laboratories are set up in this regard. The ideal cell counter for your process depends on how well it integrates into the entire system you have created and the stage of the drug product life cycle.

Inaccurate algorithms

The core functionality that allows automated cell counters to automatically count cells and measure cell viability is their software. Many factors influence the performance of the software, and one may argue that it makes or breaks the entire instrument.

Some cell types may give the algorithm more trouble than others. It is important to thoroughly test the automated cell counter using different cell types, including aggregated cells, to understand how reliable the instrument is for your purposes.

Maintaining the automated cell counter

It is vital to have access to customer support specialists and application scientists and engineers after purchasing an automated cell counter for all maintenance needs. Compared to using a hemocytometer, maintenance on an automated cell counter may cause more delays and be more costly. If a hemocytometer breaks, you can grab a new one. If an automated cell counter breaks, you will need it to be repaired as soon as possible so you can return to your operations.

Some cell counters require more maintenance than others. When it is time to fix a broken part or when poor performance slows operations, some key offerings can be crucial to avoid downtime. These include:

  • Response time of customer support
  • Replacement of broken instruments
  • Virtual support
  • Service plans

Our customer support team includes over 25 field application scientists and engineers that are ready to provide service virtually and on-site across Europe and the United States. We also provide replacement instruments to minimize delays in your operations and aim to respond to support cases within two business days.

Some automated cell counters require regular calibration

Calibration is also a regular procedure for many instruments. Although ChemoMetec products are all pre-calibrated and do not require calibration after release, many cell counters on the market do. These calibration procedures typically involve running a cell count on suspension of beads with a known concentration, and verifying the results from the instrument. Without this critical step, one cannot be entirely sure that the instrument’s performance does not deviate over time.

Conclusion

Automated cell counters offer numerous advantages in terms of speed, accuracy and efficiency, making them invaluable tools in biopharmaceutical production, scientific research and for other biotechnological applications. Automating the cell counting process reduces human error, increases productivity and provides consistent results. However, they come with their fair share of disadvantages, including high costs, operator training requirements and the need for maintenance.

Ultimately, the decision to use an automated cell counter or rely on manual cell counting depends on the specific need, budget and stage a company or a medicinal product is in.

Are you curious about our instruments and how they can help you streamline your cell-based processes? Request more information using the tabs to the right-hand side of this page and we will be in touch with you soon.

References

  1. Spyrou, G., Appelgren, D., Rosén, A., & Ingelsson, B. (2020). Sizing Up Extracellular DNA: Instant Chromatin Discharge From Cells When Placed in Serum-Free Conditions. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.00634
  2. FDA. Part 11, Electronic Records; Electronic Signatures – Scope and Application [Internet]. U.S. Food & Drug Administration. 2003. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/part-11-electronic-records-electronic-signatures-scope-and-application
  3. FDA. CFR – Code of Federal Regulations Title 21 [Internet]. U.S. Food & Drug Administration. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=211.25
  4. European Commission. EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines [Internet]. Available from: https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en#part-i—basic-requirements-for-medicinal-products

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