Many researchers are left wondering which sample type to use when testing biomarkers: serum or plasma?
Serum and plasma are not the same and are not always interchangeable. Once you understand the differences between the two, you can better judge which is the best fit for your experiments.

But even experienced scientists who know the differences are still stumped when it comes to the proverbial question: Does it really matter if I use serum or plasma?

Sometimes it does. Sometimes it doesn’t.

When the Sample Type Matters

During the clotting process, activated platelets release proteins stored in their cytoplasm along with activated proteases. We checked the levels of Vascular Endothelial Growth Factor (VEGF) in plasma and serum samples from two different donors. From one donor, we collected plasma in EDTA, plasma in heparin, and serum. From the second donor, we collected EDTA plasma, serum, and serum from a tube containing a  separation medium.

This figure shows the data from these sample types.  The serum samples are consistently higher than the plasma samples.  

When using our Proteoglycan Detection Kit, we recommend serum since heparin plasma will give falsely high levels of proteoglycan and EDTA plasma is not properly digested because of the inhibitory effects of EDTA. 

When the Sample Type Doesn’t Matter

For other analytes, the sample type doesn’t seem to matter.  The detection of placental growth factor is similar for both serum and plasma as shown in the figure below. This is particularly interesting since placental growth factor binds to the same receptor as VEGF and can form dimers with VEGF.


If the biomarker you are measuring is found in platelets, pick one sample type and don’t compare levels in plasma to levels in serum. If your detection method uses an enzyme, then EDTA might not be the best choice since it can inhibit enzyme activity. And when in doubt, get a set of samples from us and try it out.

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