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What is fetal bovine serum (FBS)?

Fetal bovine serum (FBS), also known as fetal calf serum, is used extensively by both academic biology and industrial researchers as a supplement to basal growth medium in cell culture applications. It is a rich source of proteins and growth factors that support cell growth in culture.

Serum is the amber-colored blood fraction remaining after the natural coagulation of the blood; it is typically further refined via centrifugation, which serves to remove remaining blood cells, coagulation fibrinogens, and low-solubility proteins.

Fetal bovine serum is derived from the blood of a cow fetus, which is drawn via a closed system of collection. Notably, FBS is the most widely used serum supplement for in vitro cell culture (for eukaryotic cells) [1,2].

Categories of bovine serum

Bovine serum is classified according to the age of the animal from which the blood was collected [3]:

Artistic rendering of a cow next to a bottle of Gibco Fetal Bovine Serum (FBS) with outlines of cells in the background

Note: The age of the animal is important to know as it can impact the composition of the blood and, consequently, the serum.

Fetal bovine serum composition

Composition iconFetal bovine serum provides a rich culture system known to support the widest range of cell types, including both cell lines and primary cells. The growth factors and very low levels of antibodies in FBS facilitate the versatility of this serum [4].

What is in fetal bovine serum?

Gibco FBS and Gibco Cell Culture Media in a cell culture hood with a cell culture plate, hand, and pipette

FBS contains over 1,000 different components, including:

  • Growth and attachment factors for cells
  • Lipids
  • Hormones
  • Nutrients and energy sources necessary for growth (e.g., vitamins, sugars)
  • Electrolytes
  • Carriers
  • Enzymes
  • Factors providing buffering capacity/protection from pH shifts, proteases, and toxins
  • Binding and transfer proteins

Note: Due to its undefined nature, FBS composition can vary from lot-to-lot.


FBS storage and handling

Freezer iconAs a biological substance, FBS must be carefully taken care of and appropriately stored to avoid degradation. The most effective manner of storage is by keeping the sera frozen.

FBS should be:

  • Stored at ≤–10°C
  • Thawed between 2–8°C
  • Stored and transported in consistent conditions to prevent deterioration

Because serum can be stored for extended periods of time, researchers and manufacturers will often use the same serum lot over a couple of years. However, since FBS is not chemically defined, when it comes time to replenish their supply, they try to source a similar lot with the same kind of specs as the product purchased before.

Thermo Fisher Scientific is committed to providing solutions that help ensure consistency from lot to lot, including FBS fingerprinting and the iMATCH Sera Lot Tool.

What is fetal bovine serum used for?

Eukaryotic cell iconThe primary use of FBS is as a growth supplement for in vitro cell culture, and it is typically added to basal cell culture media at a concentration of 5–10%. While other animal sera (e.g., horse, rabbit, goat, porcine, etc.) are also available and utilized for cell culture, fetal bovine serum remains the most universally employed.

Why is fetal bovine serum used in cell culture?

Fetal bovine serum used as a supplement in culture media primarily aids in:

  • Supplying hormone factors for cell proliferation and growth
  • Providing nutrients, trace elements, transport proteins, adherence, and extension factors
  • Cultivating a suitable environment for growth with stabilizing and detoxifying factors
  • Stimulating cell differentiation
A scientist pipetting Gibco FBS into media in a cell culture hood

Academic researchers as well as those in pharmaceutical and biotechnological industries have relied on the valuable properties of FBS for many years. Specific applications of FBS in research and industry include but are not limited to:

  • Animal diagnostics
  • Cloning
  • Cryopreservation
  • Stem-cell research
  • In vitro fertilization
  • Biopharmaceuticals
  • Cell and gene therapy production
  • Immunotherapy
  • Synthetic protein production
  • Viral vector production
  • Vaccine production

Want to learn more about FBS and vaccines? View our guide to fetal bovine serum in vaccine production

Benefits of fetal bovine serum use

Eukaryotic cell and heart iconThe unique biological makeup of FBS promotes rapid cell growth, thus making it a product that yields a high efficacy. In addition, fetal bovine serum contains a sparse amount of gamma globulin, higher levels of growth factors, and fewer complement proteins than both calf and adult bovine serum. This makes FBS ideal for propagating cell growth while also decreasing the possibility of mammalian cells binding or lysing in the culture, rationalizing the preference of FBS over other types of bovine sera. Furthermore, FBS contains low levels of antibodies and other growth-inhibiting components.

In addition to providing cells with many growth-enhancing factors (growth factors, hormones, nutrients, etc.), FBS can also protect cells from harmful disruptions, including:

  • Large pH shifts
  • Proteases
  • Toxic agents
  • Shear forces
  • Agents that would typically break up monolayers of adherent cells (FBS acts to inactivate these agents)

Therefore, when FBS is used, cell growth is typically:

  • Rapid
  • Consistent and reproducible
  • Lacking in undesirable changes in differentiation
  • Not hampered by the introduction of detrimental contaminants

While other animal sera, such as horse serum, may be good for certain types of applications, FBS is more universal and can function across a variety of applications, streamlining supply needs.


Important considerations for FBS use in cell culture

Person iconAlthough researchers may assume that all FBS products are of the same quality, there are several key factors that should be monitored and considered when sourcing FBS for the lab, including:
  • Supply continuity
  • Lot-to-lot consistency
  • Reproducible results
  • Price fluctuation
  • Product integrity

Furthermore, researchers rely on FBS that is sterile, filtered, and free of mycoplasma. Thermo Fisher Scientific’s commitment to quality and consistency helps ensure that each lot of Gibco sera meets the needs and standards necessary for optimal cell culture performance and growth.

Important terms to know when evaluating FBS

When evaluating FBS integrity for cell culture use, there are a variety of terms that should be understood regarding the quality and safety of the product.

TermsDefinitions
9CFR virus testingVirus panel testing according to Code of Federal Regulations, (CFR), Title 9, Part 113.53 (c) [113.46, 113.47]. Detected by fluorescent antibody.
Biochemical and hormone profileQuantification of biochemical and hormonal (estradiol, insulin, progesterone, testosterone, and thyroxine) profiling that may have impact on cell culture.
BSE statusBSE (bovine spongiform encephalopathy) is a disease for which the OIE (The World Organisation for Animal Health) has established official recognition of the sanitary status of countries and zones. Regions that have negligible risk of bovine spongiform encephalopathy (mad cow disease) have lesser biosafety risk for import.
EMA virus testingVirus panel testing according to Code of Federal Regulations, (CFR), Title 9, Part 113.53 (c) [113.46, 113.47]. Detected by fluorescent antibody.
Endotoxin testingEndotoxin is directly related to the quality of collection and processing of serum, the higher the level, the more introduction to gram-negative bacteria. 
FiltrationTriple (0.1 µm) filtration: Aseptic process that has been validated to ensure that all products meet the industry standard sterility assurance level of 10-3.
Haemoglobin/hemoglobinIndicator of proper and/or improper collection and processing of blood and/or serum. 
Mycoplasma and Mycoplasma supplemental testing (H-Stain)Direct culture and Hoechst stain. Testing indicates Mycoplasma - Not Detected.
Origin confirmationWe use a Oritain sera fingerprinting technology for Gibco sera to confirm FBS origin and eliminate the potential for counterfeit product. Learn more
OsmolalityOsmolality of FBS, a measure of the concentration of solutes like salts and sugars, should be similar to culture media to avoid osmotic shock that may impact cell viability.
Performance: relative growth promotion (RGP)The growth promotion assay measures the ability of each FBS lot to support proliferation of fastidious human diploid fibroblasts through multiple subcultures.
pH: relative pH promotionSerum acts as a buffer in the cell culture system; the pH is tested to ensure accurate cell culture quality and performance.
Total proteinFBS is rich in a variety of proteins that can impact cultured cells; the total protein in serum is measured by taking a chemistry panel of the serum.
TraceabilityComplete traceability back to original source. ISIA Traceability Certified. Learn more

Market scenarios that drive FBS availability and price

Although the quality and integrity of FBS can be monitored and regulated, fetal bovine serum is still a byproduct of the meat industry. Therefore, FBS cost and supply is difficult to manage. The added variables of the environment and geopolitical events account for a somewhat inconsistent supply. Within recent years, the price of FBS has increased by over 300% in response to growing demand and restricted availability [4].

Watch the video to learn more about why FBS prices fluctuate constantly.


History of FBS use in cell culture

Ringer's cell culture medium was developed by Sydney Ringer in 1882 and was the first instance of in vitro cultivation of animal tissue. Over the next few decades, scientific innovation led to the development of the first animal cell cultures, then synthetic media. The 1940s saw the establishment of cell lines, basal media, and research into protein-free media.

In the late 1950s, Theodore Puck first introduced the use of FBS in cell culture with the purpose of encouraging cellular proliferation. Additional studies revealed that, in addition to its ability to stimulate cell proliferation, FBS also contained a multitude of components essential to cell growth and viability (e.g., hormones, vitamins, growth factors, etc.) [5].

For several decades, the use of fetal bovine serum has been ubiquitous across laboratories worldwide. Its popularity has continued to lay in its indispensability as a supplement in cell and tissue culture applications.

The future of fetal bovine serum use

Person iconThe availability of research-grade fetal bovine serum has dramatically increased the pace of biomedical science, and as a supplement to growth culture media, it’s unparalleled. Although the development of serum-free media has provided benefits to certain cell culture applications, FBS remains the most versatile and widely used source of nutrients for cells and will continue to be the primary supplement to laboratory tissue culture media for the foreseeable future.

To help ensure quality, safety, consistency, and regulatory compliance, Gibco FBS products undergo strict testing parameters, including being ISIA Traceability Certified and Fingerprinting Origin Guaranteed.

References

Resources

Fetal Bovine Serum Basics
Learn the basics of FBS for cell culture, including information on the FBS uses, components, and the market dynamics driving this industry.

Cell Culture Basics
Learn the fundamentals of cell culture for achieving consistent results, including laboratory setup, safety, and aseptic techniques.

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