5 reasons to switch to serum-free culture media

To grow cells in vitro culture media must mimic in vivo conditions. This is commonly achieved by adding serum to a classical medium (DMEM, RPMI etc) at concentrations of 5 to 10%.

Growing concern over the poorly defined nature and variability of serum has led to the development of serum-free media and serum substitutes. Below you can read why we think it's a good idea to replace your current serum-containing media by serum-free alternatives.

Consistent, defined composition

Serum is a poorly defined culture medium component as its composition can vary considerably. Even though serum consistency has improved over the years, and new lots can be tested, the physiological variance can be quite high, leading to poor reproducibility or misinterpretation of results.

The composition of serum-free medium on the other hand is exactly known and the level of each component precisely defined. This ensures lot-to-lot consistency and eliminates the screening of new serum lots.

Lower risk of infectious agents

Contamination of serum with viruses, bacteria, fungi or BSE has been a concern for many years. For biopharmaceutical manufacturers this has led to the elimination of all animal derived components from the manufacturing process.

For research, serum-free media also offer the benefit of eliminating the risk of infectious agents while supporting the growth of a wide range of cell types.

Lower risk of interfering components

Serum components may also bind, degrade or otherwise interact with substances added to the medium. This may influence the observed effect and lead to false conclusions.

Serum-free medium has fewer possible interfering factors and if an interaction is observed, it can be more easily controlled.

Less contaminants

The concentration of serum proteins is generally much higher than the level of a recombinant protein produced by mammalian cells. Serum proteins are thus a major contaminant of the target protein. And if the target protein is related to a serum protein, it may be difficult to separate the two.

In serum-free media the protein concentration is low and, unlike serum, the composition is known. As a result, the target protein is easier to purify in fewer steps and with higher recovery.

Avoids ethical issues

Based on what is known about the harvesting process of fetal calf serum it can be said that animal welfare is better served by serum-free alternatives.


Despite the major benefits of serum-free media described above, there are a few drawbacks that should be considered. First, it takes time to adopt a particular cell line to serum-free medium. The cells will have to be weaned from serum gradually and some cell lines may require the addition of growth factors.

Second, serum-free medium does not contain sufficient protein to protect cells against shear. The addition of Pluronic F68 or PEG or alternative supplements may be required.

Finally, adherent cell lines require an extracellular matrix on the culture surface, part of which is provided by serum. Therefore, when using serum-free medium the culture plates should be pre-coated with a fibronectin, laminin or another suitable alternative.


Serum-free cell culture media are an excellent alternative to standard serum-containing media and offer several major advantages. The commercial availability of optimized serum-free medium and serum substitutes has made it easy to obtain and use. As a result serum-free media deserve serious consideration for the culture of a wide variety of cell types.