Screening with Cell Based Assays… Imaging or Flow Cytometry?

Author: Thomas Duensing, Ph.D.; Published: Mar 14, 2011; Category: Drug Discovery, Flow Cytometry; Tags: High Content Analysis, high throughput flow cytometry, Suspension Cells; Comments Off

YES!

As most of you know, we here at IntelliCyt have developed the HTFC Screening System; which is a high throughput screening platform using cell based assays. What is unique about our system is that it uses flow cytometry to measure cellular fluorescence. What you might not know is that our founder, Terry Dunlay, was also the co-inventor of High Content Screening and a co-founder of Cellomics, which pioneered the field of imaging based high content screening. This gives us a unique perspective, having developed both imaging and flow cytometry based screening products.

So back to the question; imaging or flow cytometry? As you might have guessed, I see these platforms as complementary technologies. Let’s look at flow cytometry first. Very simply put, this is a very powerful technology that measures fluorescence signals associated with cells in suspension as they pass through a laser based detection system, one cell at a time. This enables a couple of important features. The first is speed; thousands of cells can be analyzed in one second. This has obvious advantages in terms of statistical robustness. What’s more, multiple colors of fluorescence are detected on each cell simultaneously. This means that it doesn’t take additional time to measure additional parameters. Another valuable feature is that flow is perfect for suspension cell analysis. Suspension cells, including primary cells of the blood and bone marrow system and cell lines representing the immune/inflammatory system have largely been underutilized in high throughput screening environments. With the introduction of high throughput flow cytometry, screening assays employing these important cells are now being incorporated into drug discovery screening campaigns.

Now let’s look at imaging. High content screening platforms utilizing fluorescence microscopy have revolutionized the drug discovery industry. HCS platforms use fluorescence microscopy to capture images of cells in microplates, and then employ sophisticated imaging algorithms to interpret the fluorescence signals present in each cell. Analyzing cells by imaging in microplates thus enables the combination of throughput with spatial measurements. Imaging, then, is great for testing the effects of compounds (or other treatments) on readouts like subcellular translocation of molecules, cell morphology and even cell motility. Because the majority of these platforms work best with immobilized cells, they are perfectly suited for analyzing adherent cells.

This is an exciting time in cell based screening. Each year new platforms are becoming available for high throughput analysis of cells, which gives scientists powerful tools for drug discovery and systems biology. Now scientists have a choice in selecting the most appropriate cells –whether suspension or adherent- in which to perform small molecule or biologics screens, or when performing high throughput systems biology experiments.