Advancing Flow Cytometry With High-Throughput Analysis and Automation

Flow cytometry is quite a complex technology, entire books have been written explaining the technical details of how it works. For anyone who would like to learn the principles of flow cytometry, we have some really great resources including guides, workbooks and free online learning on the Bio-Rad website.

A really easy way to understand what a cytometer does is to think of a microscope. When you look down a microscope, you can get an idea of how many cells you have and maybe some idea of their relative size. If you add some sort of stain that sticks to some cells but not others, you can start to differentiate cells.

In a flow cytometer, the cells are suspended in liquid and move very quickly one by one through the detectors. With a typical microscope, you may see a couple of hundred cells at a time. With a cytometer, it’s in the region of tens of thousands of cells per second and that’s the key difference; the number of cells that can be analyzed. Another advantage is the number of stains or parameters that can be used at once. Because we use lasers to illuminate the cells, cytometers can detect dozens of parameters simultaneously.

This is valuable for cell analysis because it allows for extensive and detailed examination, thanks to the large number of cells that can be analyzed simultaneously and the multiple parameters that can be assessed at once. It means that we can look at a huge number of cells and get a lot of information about each one of those cells very quickly. 

The ZE5 Cell Analyzer is a very versatile instrument with up to 30 parameters, making it suitable for simple or very complex assays. It’s also easy to use and learn so it can be a great benefit to just about any lab. It excels in applications that require very high throughput or in labs that are busy with a heavy demand for flow instruments. It’s also been designed to be a true walk-away system – something that many flow users are not used to because a lot of systems require constant attention. The fact that you can set the instrument going and then confidently walk away means that it can free up the researcher’s time to be more productive.

The key differentiating factor is the speed at which experiments can be performed. It has an industry-leading data collection rate of up to 100,000 events per second, which can really speed up rare cell analysis. It can also process a 96-well plate in under 15 minutes, making it ideal for screening applications. The ZE5 Cell Analyzer’s suitability for automation — a strong focus of the SLAS conference — is another stand-out feature. 

There are many considerations when investing in this type of instrumentation. The number of lasers and detectors needed, price point, suitability for high-throughput applications and automation, ease of use and reliability are all important things to consider.

Everyone’s needs are slightly different. If you need an instrument that can handle a very broad range of assays, increase your flow cytometry productivity or even just your productivity in general, you should consider the ZE5 Cell Analyzer. But if your main workflow involves a high volume of medium to high complexity assays and time to results is critical, then really it should be right at the top of your list because no other system does that better. 

There are many challenges relating to sample preparation. But, when it comes to instrumentation, signal-to-noise ratio and resolution are important. The type of detectors used and how those detectors are set up make a big difference here.

The ZE5 Cell Analyzer uses photomultiplier tubes, which have optimal signal-to-noise characteristics, and a dedicated small particle detector to give improved resolution for exosomes and bacteria. Both those features make it well suited for these types of applications.

Sample preparation is key to generating accurate data. As everyone knows, if you put garbage in you get garbage out. But that is not to say that the instrument you use makes no difference at all. For example, samples often must be kept cool to avoid temperature artifacts. If you are collecting data for an extended period, that could start to become an issue. However, the ZE5 Cell Analyzer has integrated sample cooling to avoid temperature artifacts.

Also, poorly prepared samples can often aggregate, which can cause a lot of problems for any instrument, but the ZE5 Cell Analyzer has integrated sample agitation and is resistant to blockages.

Finally, upstream automation of your sample preparation probably represents the ultimate means of standardizing sample quality, so using an instrument that is ideal for integration into robotic work cells is the obvious solution.

I think, in the past, automation was a bit of an afterthought for many flow cytometer manufacturers. A case of figuring out how to make a cytometer work for automation rather than being central to the design. In contrast, the ZE5 Cell Analyzer was developed with automation in mind from the start. It has a host of features like automatic cleaning on shutdown, automatic fault detection and recovery that just wouldn’t have been possible otherwise.

Additionally, there has been historical acceptance of flow cytometry as a labor-intensive technique that involves many hours in front of an instrument gathering data. We are moving away from that with the ZE5 Cell Analyzer, allowing users to simply add their samples, press go and come back later to collect the data. Once users see that a hands-off approach is a feasible way of working, it will be a short leap to maximizing those benefits by adding automation.