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Something that annoys me to an arguably irrational level about the “serum-free media” space is how confusing the vocabulary gets once you start digging.
I’ve lived and breathed this stuff for the better part of a decade, and it still sometimes takes me a beat to understand a serum-free supplement. You see these words everywhere: Serum-free. Animal-free. Chemically defined. Reproducible alternative to FBS. A quick Google and you’d be forgiven for thinking there are a wide variety of equivalent, high-quality serum replacements out there. But these words can be layered together in ways that blur real scientific differences. First, some formulations simply replace FBS with another complex biological supplement. This is a reasonable strategy; for example, replacing FBS with human platelet lysate in cell therapy manufacturing to reduce cross-species risk. But you still have batch-to-batch variation. ”Animal-free” removes animal origin risk but can include other undefined extracts. Love this for ethics or regulatory positioning. It's less useful for having control over what’s in your media or batch reproducibility. “Reproducible alternative to FBS” has given me the ick several times. I’ve seen this wording, dug into the supplement, then realized it isn’t chemically defined in the slightest. There may be process consistency or tighter QC than raw serum but if the inputs are undefined, reproducibility has a ceiling. “Chemically defined” is the gold standard. Every component and concentration is known. This one tends to be safer, but there are levels. You’ll sometimes find purified bovine serum albumin or similar components, despite the fact that albumin is serum-derived and carries residual batch variability depending on purification and lipid loading. To be clear, this is how the category evolved rather than a criticism of any specific product, and perfect shouldn't be the enemy of good. People come to me because they’re over FBS for a lot of different reasons: Ethics. Reproducibility. Regulatory risk. Cost. Most existing serum replacements were designed to tackle one or two of these, not eliminate all of them simultaneously - fair. Still, when we built our replacement, we were deliberate about the vocabulary: fully chemically defined and fully animal-free, designed for reproducibility. I am regularly challenged on these terms by people who’ve been burned before - by products that were "reproducible" but not defined, or animal-free at the product level but not across the supply chain. And frankly, I love it, because I know our language matches the technical reality. The goal has always been to provide an alternative that can realistically compete with FBS on price, sustainability, regulatory AND experimental control/reproducibility across time, labs, and geographies. This vocabulary, and how we use it, matters a lot if we as scientists want to achieve that.
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To help prospective customers quickly understand the breadth of what FRS Pioneer can do, we've put together this helpful diagram. As always, please get in touch if you have any questions about using FRS Pioneer in your laboratory.  There’s a hidden modelling assumption baked into many AI- or ML-enabled biological datasets: If your models are trained on cell culture data, your media formulation is part of the model.
Here’s how a default choice I’ve seen teams make early on, accidentally becomes expensive to unwind later: When companies using cell biology to train predictive models are first established, cell culture processes are often given relatively minimal thought. Many companies treat this as basic infrastructure, while the critical part of the model sits downstream in protein folding, functional phenotypes, or biological performance metrics. Unfortunately, by starting from standard cell culture processes, many of these companies begin using processes that rely on fetal bovine serum or other undefined, variable cell culture media inputs. These model datasets are intended to become moats, but they’re only as robust as the conditions under which they were generated. Serum and other animal-derived nutritional supplements influence growth rate, shape stress responses, and impact metabolism, signaling, phenotypic baselines, and every facet of cell biology. From a modelling perspective, this means your training data can encode variability that isn’t obvious until conditions change. Unsurprisingly, this shows up in the data set as unexplained variability or performance drift. The major challenge is that this risk is easy to miss early on, when your model data is fairly limited, e.g. it’s been collected in one laboratory, using one batch of FBS, under “pretty constant” conditions. Usually, this risk rears its ugly head when datasets grow. Suddenly, you’ve used up your batch of FBS and you’re switching to a new one, or you’re transferring your findings to a different lab/company/site and the model’s results aren’t holding up. At that point, performance drift is sometimes blamed on “biology” or “model issues,” when it’s at least partially due to the “basic” cell culture processes that were popped in place three years ago. Reality is, if your experimental system isn’t controlled, your training data isn’t either. This will have implications for your model. My suggestion here is simple; think about this early! Media formulation should be a deliberate modelling decision, not a background reagent choice that we just roll into because “oh yeah, the literature says DMEM + 10% FBS so let’s go for it.” Teams that commit early to chemically defined, stable culture conditions are less likely to face costly or time-consuming surprises when models are applied, transferred, or scaled. Stable inputs in, more reliable models out, and a healthier data moat over time. That tends to keep everyone happy! Most scientists don’t think about this, but if you’re culturing cells with FBS, you’re also including a wildly batch-variable, undefined mix of protease inhibitors with downstream consequences for cell biology. The presence of protease inhibitors in FBS is critical for passaging cells with trypsin; these proteins are responsible for deactivating trypsin (assuming you’re using FBS-containing media to quench the reaction, rather than a separate trypsin inhibitor). Unfortunately protease inhibitors are more problematic during the culture process than most people realize - but odds are you’ve never even thought about the impact they’re having on your cells. Protease inhibitors regulate processes like ECM turnover/remodeling, cell-matrix signaling, or migration, invasion, and differentiation. So adding an undefined mix of protease inhibitors to your cultures, courtesy of FBS, inevitably has an impact. This is particularly relevant for studies linked to fibrosis, cancer invasion, differentiation, or organoid/3D culture systems. Here’s where it gets even more interesting: many scientists assume growth factor variation drives most of FBS batch variation, and this does play a role. However, protease inhibitor variation is very much present, largely unappreciated, and has major implications for our research studies. These variable protease inhibitors control how much cells can cut up and remodel their surrounding matrix. If one serum batch inhibits proteases more than another, cells will migrate differently, invade differently, remodel ECM differently, and respond differently to exactly the same experimental signals. So when it comes to publishing research results using different batches of FBS, ECM-related results can vary substantially. That’s a big reason experiments involving migration, invasion, fibrosis, or 3D cultures can be so hard to reproduce. And this is also why many scientists whose experimental readouts depend on ECM dynamics can and should consider working with chemically defined systems.
As always, literature below if you're keen to dive deeper! For more reading: Page-McCaw et al. - for a review on how protease activity controls ECM remodeling, signaling, and cell behavior. https://www.nature.com/articles/nrm2125 Bonnans et al. - shows how protease regulation impacts cancer and fibrosis. https://www.nature.com/articles/nrm3904 Gjorevski et al. - A deeper dive into how chemically defined, tunable systems are important for reproducibility in the context of ECM composition and remodeling studies. https://www.nature.com/articles/nature20168 Not FBS specific, but one of the older papers on protease inhibitors in serum. Love a good study from the 1950s: https://pubmed.ncbi.nlm.nih.gov/14946322/ If you scroll through the formulations for most foundational basal media (DMEM, RPMI, MEM, etc), here’s what you won’t find: Lipids.
These basal media were created over 50 years ago, before lipid metabolism and membrane biology were well understood. As such, you won’t find key fatty acids, cholesterol, and the delivery systems required to supply them to cells for efficient uptake. This is just one of the many, many reasons that scientists include fetal bovine serum in their cell culture media; it delivers lipid complexity. However, you'll notice a surprising number of serum-free media recipes don’t include many - sometimes any - lipids. This may appear okay for short-term cell growth, or even growth of particularly robust cell lines. But it does have an underappreciated impact. Without lipids, cells often end up with altered membrane composition, shifted eicosanoid pathways, ER stress, and/or rewired inflammatory signaling. Phenotypes like morphology, proliferation rate, and oxidative stress sensitivity often reflect this underlying lipid deficit. This is something we thought a lot about when developing our chemically defined FBS replacement. And it’s something for you to think about if you’re trying to eliminate serum from your cell culture; are you incorporating the right lipids for your cells, and do you have the right strategy to ensure their bioavailability? As always, journal articles below if you want to dive deeper 😊 https://pmc.ncbi.nlm.nih.gov/articles/PMC5661806/ Following a recent article for Beyond Animal Research in New Zealand about the use and limitations of foetal bovine serum (FBS) and Media City's alternative 'FRS Pioneer', I was asked to put together a similar article for Animal-Free Science Advocacy in Australia. Here is a link to the article: Foetal Bovine Serum finally has a superior replacement alternative  Let me tell you what’s driving your FBS batch-to-batch variation; it’s similar to how bear serum varies between summer and winter months (yep, see the comments for that absolute gem of a study).
At first glance, “batch variation” sounds like a QC problem but most biologists will know FBS variability comes down to its animal-derived nature. FBS is essentially a biological snapshot of fetal physiology at a specific point in gestation. The fetal blood is pooled, essentially in an attempt to somewhat standardize the FBS. What scientists might not know, is pooling can help mitigate shifts due to: 🐮 Fetal age: As fetuses mature, albumin levels increase, immunoglobulins rise, and lipid profiles shift. Pooling smooths this out to an extent. 🐮 Stress at harvest: Cortisol and catecholamine spikes in mama cow alter glucose, lactate, and metabolic profiles. Pooling dilutes these acute stress-related changes. Pooling does not (particularly) help mitigate changes due to 🐮 Maternal diet: Micronutrients, fatty acids, and trace minerals pass directly from mama to fetus. 🐮 Seasonality: Pasture quality, climate, and feed composition change micronutrients, hormones, and fatty acids in serum. FBS collected in winter is measurably different from summer (like bears!). 🐮 Geography: Soil composition, water mineral content, and regional feed practices influence trace elements, metal-binding proteins, and vitamin levels found in serum. And this is why you’ll see differences in cells cultured using FBS from South America versus the US versus Europe versus New Zealand. _______ We spent years developing an animal-free replacement for FBS that doesn’t have batch-to-batch variation. To do that, we had to benchmark against FBS - multiple batches of FBS. It’s tough to establish a baseline of “this is what good looks like” when your standard is intrinsically variable. For balance, we worked with ~6 FBS batches. As an extreme example, one batch straight up did not grow our AD-MSCs. This is why scientists batch-test and stockpile FBS to ensure consistency across a series of experiments. Once a given batch of FBS is gone, it’s impossible to precisely replicate the mix of proteins, lipids, metabolites and trace elements. This is also why — where feasible, because it certainly isn’t always feasible (yet) — growing cells in chemically defined media is a good move for scientific reproducibility. Interesting science below if you want to dive deeper, including that study in which mouse cells were cultured with bear serum from summer versus winter, aka hibernation season. https://pubmed.ncbi.nlm.nih.gov/34336951/ - Winter/Summer bear serum, and how it maybe can be used to identify helpful therapeutic agents https://pubmed.ncbi.nlm.nih.gov/39617443/ - Selenium variation in FBS from different geographies....and the result on cells. https://pubmed.ncbi.nlm.nih.gov/29196597/ - Impact of different batches of FBS on cells https://pubmed.ncbi.nlm.nih.gov/1153408/ - An older paper, in which different FBS batches were quantitatively profiled Scientists, I’ll level with you: when I started sharing publicly about building a biotech company without raising VC, it was easy to imagine what a post describing the wrap up of company operations would look like. It was much harder to imagine commercial launch…and yet here we are. Happy launch day. 🥂
One morning a few months ago, something pretty cool happened: Media City Scientific made our first sale. In the afternoon, something even cooler happened: we made our second sale. Today we publicly launch FRS Pioneer - a chemically defined, animal-free replacement for fetal bovine serum (FBS) that’s drop-in and easy to use. How did we get here? ➡️Obsession: indulge me because the word is bandied about, but the formula was a labor of love. I clocked eight days away from a biosafety cabinet in 2025. Four of them were after I gave birth. ➡️Support from Australian scientists: When not in our lab, I was in external labs. We dedicated an entire year to piloting FRS, swapping it directly for FBS across a range of every-day activities in different lab setups. Varied processes for passaging, dilution in different basal media, mixing freeze media, running standard assays, growing cell lines, other cell types, and more. To break a 50+ year old FBS habit, FRS needed to be genuinely user-friendly, and our earliest pilot testers are the real MVPs for helping us get there. __________ FRS Pioneer is not a perfect replacement for fetal bovine serum for every use case, but I’ve been around the entire block when it comes to serum-replacement. I haven’t found anything that comes close to matching its ease of use or broad functionality. Our earliest users have started re-ordering and have encouraged me to launch, so here we are. Our website has data. We’re open for orders. With every order, you’ll get personalized, hands-on support from Katie. We make going serum-free or serum-reduced easy - whether that involves FRS Pioneer, your own in-house media development efforts, or something else. We are an Australian company that will start small but scale globally. We’re scientists too, so talk to us if you want our honest opinion on how FRS Pioneer will perform in your system. ________________________ There are many people reading this who have pushed us along in small and large ways. Thank you. A few years ago, we were quite literally dry walling an R&D lab. Last week, we were putting the final touches on our ISO documentation, negotiating supply chain agreements, and talking to cGMP facilities. There’s a big lift to go, and there will certainly be challenging days ahead, but I’ve become quietly convinced it’s all possible. Cleaning up packaging and empty boxes isn't the most glamorous task. Here's how we've approached it to make it a little more fun and eco-friendly!  It's been a truly massive 2025; if I’ve learned anything from piloting our chemically defined FBS replacement in 15+ Australian laboratories, it’s that even the most basic of cell culture activities varies between labs. Temperature, passaging reagents, thawing processes, cell culture plates; every single one of these variables impacts how cells transition to serum-free media. Unfortunately, these are exactly the kind of insights that don’t make the most exciting scientific papers. Useful insights are hidden in failed experiments that never get shared. Media City Scientific is now preparing for launch of our first product. We’ve thought a lot about how important it is to ensure the transition from FBS to our serum replacement product is super, super smooth. That’s why I’m committing to things that don’t scale; to support early adopters, I’ll offer 1:1 time with every single customer. But as we scale - even globally - we want to see that kind of tailored support scale too. That’s why we’re exploring a collaboration with Carmen Kivisild, PhD and her team at Elnora AI. Their platform is designed to capture negative data and turn it into shared knowledge, so labs can avoid repeating the same dead ends. Together, we’re asking: could the combination of deep scientific expertise and a trained GPT agent effectively support labs to transition away from serum use? We’re hoping to identify a pilot lab anywhere in the world to test this with us - you’ll get all of Media City’s scientific insights, wrapped up alongside a GPT to test whether this is an efficient way of making the transition. If your lab is considering a move away from FBS, or if you have stories about a transition-gone-poorly, let us know! Taking notes over here to make sure adoption can be super smooth ✏️  |
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