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Our CSO Katie is doing a webinar on serum-free media development!
Whether you're thinking about bespoke, high-density production media or broad-spectrum FBS replacement for improved scientific reproducibility and control, Katie is giving a short, highly practical webinar next week. This is targeted at scientists new to serum-replacement, but it's also sprinkled with recommendations which should be helpful even for the most experienced. Super biased, but we think it should be pretty useful for anyone who does cell culture - so join us! Link to event: https://lnkd.in/df5Nt-7Z
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New application note, in partnership with Qkine and Elita! See how FRS Pioneer supplemented with Qkine growth factors out-performs FBS for AD-MSC culture. Most scientists move to a new batch of FBS by testing their cells in a few different batches, then moving forwards with the batch that "works best" for their cells. If you use FRS Pioneer to reduce your serum use by 90%, you also substantially reduce the risk of serum-derived variability impacting your seed train. Or, go fully chemically defined and eliminate the variability of serum all together. FRS Pioneer makes developing bespoke media for your particular cells easy. Read full application note > mcs_qkine_admscs.pdf Check out the products used in this application note: FRS™ Pioneer – Fetal bovine serum replacement > https://lnkd.in/gwqvyNVZ GECKO™ – adherence solution > https://lnkd.in/gFCXd_FT PDGF-BB (Qk044) > https://zurl.co/tuxOx Highly potent FGF-2 (145 aa) > https://zurl.co/vgfXV  Hard to believe: same cells, same media, same time point following seeding. Cell adhesion is highly underrated when it comes to serum-free cell culture. If you’re culturing cells in FBS-containing media, you’ve probably thought very little about adhesion and spreading because the development of TC-treated plastic in the 1960s became the infrastructure for serum-containing cell culture. If you’ve tried to move to chemically defined media, you may have seen something like images A or B and thought “wow, this serum-free media is awful”. This is not a faulty chemically defined media (see panels C and D for proof!) This is what an adhesion problem looks like. These are MCF-7; an epithelial line which is notoriously finicky when it comes to attachment and spreading in serum-free media. Fix the adhesion problem, and you'll see the serum-free media is providing the nutrition this line needs to grow happily in fully chemically defined, animal-free conditions. This is why we developed and validated adhesion reagents alongside FRS Pioneer, which include a chemically defined adhesion mix as well as recombinant vitronectin. Now, typically the serum-free media world relies on coating plates with adhesion protein because the world doesn't yet have the infrastructure-equivalent of the TC-treated plate for serum-free media. However, if you currently coat your plates....and you'd like to be able to skip this step, plus reduce the adhesion proteins you’re using by 90%+ and still get really nice adhesion.......talk to me. We have something new you’ll want to try.  If you’re curious:
A: No pre-coating B: Pre-coating with laminin C: Pre-coating with optimised blend of fibronectin and vitronectin (Media City Scientific GECKO) D: Pre-coating with 10% FBS-containing media (adhesion control). Surfaces were coated with protein diluted in PBS-/-, 1hr incubation at 37 degrees. Remove coat, plate cells in media supplemented with 10% FRS Pioneer. Here’s what I’m seeing from the NAMs space lately, following the Non-Animal Technologies Network (NAT-Net) Vanguard Symposium in Sydney last week: → My favorite talk was linked to a new strategy for dynamic control of cell exposure to signals which drive cell fate decisions. As someone who has spent a lot of time thinking about the complex mixture of signaling molecules that is fetal bovine serum, I found this an interesting new technology with a number of commercial implications. → A huge range of new organoid models were presented; cell culture media and surface stiffness are two key parameters that often help optimise a given model. Reproducibility challenges linked to handling were repeatedly cited; robotics are often the solution of choice. For one model, it took over a year to screen over 20 different combinations of cytokines. That’s a lot. I’m not sure what approach they took here, but I would love to see more academic scientists reach for design of experiments-based methodologies or Bayesian approaches to accelerate these kinds of studies. → I’m seeing increasing overlap in a specific challenge faced by two different groups of scientists. On the NAM side: scientists trying to replace animal dosing studies with cell-based dose-response data. On the biopharma side: scientists running large scale cell-based assays to discover new drugs. The challenge is that albumin present in fetal bovine serum binds certain drug candidates, which impacts potency. FBS batch variability makes this more problematic. However, our animal-free FBS replacement contains a much lower albumin content and as a result, we’ve worked with scientists on the biopharma side to switch their cultures to FRS in order to remove that confound and inconsistency. This means cleaner screening data and an easier case to make to regulators on assay reliability. And of course it was great to be able to share some of the results of our FRS pilot studies, completed across a range of Australian and NZ labs over the last 18 months. Thank you to those labs for allowing me to present your data and thank you to Beyond Animal Research for support of the NZ pilot studies! P.S. NZ scientists, this access program is ongoing, so please reach out if you are keen to test some FRS Pioneer!  Cambridge, UK and New South Wales, Australia – 7th July 2026 – Qkine, Ltd. today announced it will begin global distribution of Media City Scientific’s FRS™ Pioneer, a chemically-defined, animal replacement solution to support routine cell culture in traditional basal media. The main research challenges with fetal bovine serum (FBS) are that, whilst it works well as a growth supplement, it is biologically undefined, variable, hard to control and comes with significant ethical and moral concerns. That creates problems for reproducibility, interpretation and clinical transability. There is now a genuine replacement alternative in FRS™ Pioneer, which shifts the cell culture media paradigm from the “black box” to a controlled input, trading undefined complexity for an explicit, engineerable, and reproducible choice. “Working with Media City Scientific is an absolute dream with the FRS™ Pioneer product completely aligned with our Qkine 100% animal-free, chemically defined non-negotiables. This is a potentially game-changing product for life science research and translatable pharma & biotech. Customers can now decide on one hand between continuing to be accepting and supporting the unknowns and risks which are associated with FBS whilst now on the other, proactively choosing to switch to a chemically-defined, animal-free FBS replacement which will work consistently, reproducibly, and in the meantime removing the supply chain risks associated with agricultural supplies of fetal calves.” Rob Nixon, Commercial Director, Qkine. “Scientists around the world are already using FRS™ Pioneer to make serum-free cell culture easy, at a time when life science research is undergoing a step change away from undefined animal products to defined inputs. Qkine’s range of recombinant animal-free proteins are a perfect complement to FRS™ Pioneer. Together they enable complete serum elimination across the most nutritionally demanding cell types which underpin many next generation therapies. Media City Scientific is excited to be working with Qkine to support many more scientists in making foetal bovine serum a fragment of history.” Katie Day, CSO, Media City Scientific. About Qkine Qkine manufactures high-purity, animal origin-free growth factors, cytokines, and other complex bioactive proteins for life science applications, including stem cell and organoid culture. Headquartered in Cambridge, UK, Qkine addresses fundamental biological, quality, and scale-up challenges by integrating proprietary recombinant protein production processes with protein engineering approaches, delivering more reliable tools for research and bio-manufacturing. Actively supporting and innovating in emerging fields such as 3D stem cell models, organoids, cellular agriculture, cell therapy, regenerative medicine and organ-on-a-chip, Qkine aims to accelerate the impact of these technologies on human health and wellbeing. Please visit qkine.com, email [email protected] or follow us on LinkedIn. About Media City Scientific Media City Scientific is an Australian biotechnology company committed to making serum-free adoption both practical and accessible for researchers and manufacturers worldwide. Its flagship product, FRS™ Pioneer, is a fully chemically defined and animal-origin free serum replacement engineered to support robust growth across a wide range of cells without the lot-to-lot variability or ethical concerns linked to fetal bovine serum. For more information visit mediacityscientific.com, or follow on LinkedIn  So, you want to grow your cells without fetal bovine serum? Be prepared to account for ALL of the myriad roles this golden cow elixir is currently playing in your cell culture.
Here are just a handful of the many roles FBS is playing: Driving adhesion: Fibronectin and vitronectin are the key proteins found in serum which coat plastic surfaces and help cells stick. Remove serum and many adherent cell types won't attach. Failure mode: Wonky, raised morphology or floating cells. This commonly reads as a viability issue, when you actually may be really close and just need to start coating your plates with adhesion protein. _________ Delivering proliferation signals: Serum contains a complex, variable mixture of growth factors at biologically active concentrations. Different cell types often require different signals. Failure mode: Slowed growth, usually within a few days. _________ Buffering & antioxidant activity: Serum contains a variety of antioxidants which stabilise the culture environment. Without these agents, oxidative stress accumulates. Failure mode: poor cell health, which worsens if your cells are seeded at lower-than-optimal densities. _________ Source of lipids: Many cells need exogenous lipids, and yet lipids are nonexistent in most basal media. Failure mode: This usually shows up after 3-5 passages, after intracellular stores have been depleted. _________ Source of trace elements and hormones: These are present in serum at concentrations that are often important for primary cells and differentiation-sensitive applications. Failure mode: Cells grow but behave differently, for example unexpected differentiation or altered morphology. _________ Provides a carrier protein system: This allows fatty acids, hormones, and other small molecules to be shuttled in and out of cells. Failure mode: This one usually shows up pretty quickly. _________ A serum-free medium that addresses all of these simultaneously, and appropriately for a broad range of cell types is quite challenging to formulate. I’d know! However, media development can be fairly efficient if you’re focused on one specific cell type. And what I find particularly interesting is that when an adaptation process goes wrong, the failure mode can actually be quite diagnostic if you know what to look for. Somewhat forwards planning, but I'll be going deeper on all of this in a free seminar scheduled for August. We’ll chat about what a well formulated serum free system actually needs to do, plus how to troubleshoot each of these functions. (Big thanks to Sarah Farrow for suggesting this!) You can register here: https://lnkd.in/gpJqgbJK So, you've moved your cells to a serum-free media and now they look bad. Been there 🙃 Here's what to check first, because your cells' disapproval might have nothing to do with the cell culture media formulation you've chosen.
1. Remove or reduce antibiotics by 5-10x FBS binds and sequesters common cell culture antibiotics, so the activity level in culture is reduced compared to serum-free cultures. "1X" antibiotics in serum-free culture might impact your cells more than you'd expect. 2. Gentle passaging wins FBS covers all manner of cell culture sins. Serum-free cultures often require gentler handling; minimise exposure to passaging reagents, keep cells and wash media warm, and try Accutase or TrypLE over trypsin. Trypsin also isn't inactivated by most serum-free media, so something to keep in mind! 3. Adaptation has an impact Weaning cells gradually into a new media is gentlest on the cells and typically recommended. If using a direct adaptation process, move the cells into their new media when they aren't facing any other kind of passaging or thaw-related stress. For adherent cells, this means letting the cells attach to the plate and enter the exponential growth phase before performing a 100% feed to new media. 4. Adherent cells lifting up from the surface, looking like a viability issue? Rule out an adherence issue before playing with the media formulation. Impaired attachment or spreading can very, very easily read as a viability issue, but requires a different trouble-shooting approach. Look for debris, check viability empirically, and consider eliminating FBS for the first time mid-passage, so (as much as possible) you can decouple the impacts of the media on viability/cell growth versus on attachment. Not totally comprehensive, but the check list I wish I had when I started working in serum-free media dev ~6 years ago! Fetal bovine serum is this rather quite pretty reddish-amber colour, but most scientists don't think about its color much, except along one of two lines of thought: 1) "yep, checks out, it's a blood product" or 2) "this FBS looks weird, what's going on?"
We run into this when I drop off bottles of FRS Pioneer to research institutes for their regular FBS batch testing ritual. FRS is clear, so unfortunately it's not exactly a blinded head-to-head comparison. The colour of FBS comes down to hemoglobin and its breakdown products. These heme-derived pigments carry over from blood collection and processing, which can vary from batch to batch. Because it’s commonly used as a processing quality indicator, certificates of analysis often flag FBS hemoglobin content. The same is not true of most sources of variability in FBS. These variability sources range from the well-known, for example growth factor concentration variability, but extends to protease inhibitors, oxidant capacity, miRNA-containing extracellular vesicles, and dozens of other parameters which modulate cellular biology in completely unaccounted for ways that most scientists never ever think about, let alone record in the methods section of xyz journal. So you've got some options. Moving to 100% chemically defined media eliminates this variability entirely, but FBS reduction also has a meaningful impact. The research institutes we work with are typically considering reduction of standard FBS concentrations down to 1–2%, and at that level you've already cut a significant fraction of the batch variability. Plus much as we all love our ritual FBS batch testing processes, wouldn't it be even lovelier if it happened once a decade? As always, journal articles below if you're keen to dive deeper! FBS batch variability - https://www.sciencedirect.com/science/article/pii/S3050620425000429 Protease inhibitor deep dive and sources - https://www.linkedin.com/posts/kathleenbashantday_most-scientists-dont-think-about-this-but-activity-7416587209304203264-XT5T?utm_source=social_share_send&utm_medium=member_desktop_web&rcm=ACoAABxyS3cBZRJoB-cKhs2ybXkT-p4uHHtCnJk miRNA extracellular vesicles deep dive and sources - https://www.linkedin.com/feed/update/urn:li:activity:7431801402559209472/?originTrackingId=MQz2KBX26vsc%2FLqOCAlJsA%3D%3D Behind the scenes of building a biotech company: It’s been about 6 weeks since we’ve started shipping out our chemically defined FBS replacement every Monday.
We ship, I refresh my tracking app incessantly throughout the week, and we learn new things about new countries' import processes every single week. On the upside, I came into this accustomed to Australian import (one of the more complicated bars), so things have been smooth sailing more often than not. The real world humbles us but also enthuses us. User guides get improved to prevent mistakes during onboarding. We publish new data on our website showing the limits and capabilities of the product. Folks have success with new cell lines and we add them to our tally. In the background, we pull together application notes for fully chemically defined primary cell culture and operationally easy adherence in serum-free systems. We fall into a regular manufacturing and QC cadence; it’s boring and predicable, just the way I like my manufacturing processes. In a few months, we’ll know even more about product performance and edge cases. We’ll start sending product to distributors globally, to make FRS more accessible to folks outside Australia. We’ll scale up the size of each manufactured batch. And I guess that’s how a “real company” is born. Only took a few years! Trends I’m seeing in the cell culture space lately:
→ AI meets biology is accelerating the already-in-progress trend towards chemically defined research tools. This is logical. If you’re training models using cell culture data, you want the inputs as clean and consistent as possible. For example, this makes the variability introduced by FBS more noticeable as well as problematic. → Completely anecdotal but there seem to be some bad batches of FBS circulating. I’m hearing from scientists who have used fetal bovine serum for years, but suddenly - despite certificates of analysis and in-house batch testing - their latest batch is testing positive for problematic viruses or has heavy precipitation/flocculants. → Cell culture media optimisation platforms are becoming more and more advanced. The result is highly specialised cell culture media built for specific cell types allowing for faster proliferation rates, cheaper costs per liter, and higher densities than ever. → Despite these advanced cell culture media, there are plenty of scientists looking for “this is easy to use and it grows the six different types of cells that my lab grows” instead. Knock out serum replacement (KSR) seems to be the best known "serum replacement", which is kind of interesting because it was designed primarily for pluripotent stem cells and usually doesn’t substitute well for serum in most other cell types. → In this vein: there’s increasingly a natural split between “exploratory biology media” and “production media.” Highly optimized, specialised media are necessary for high densities or cost optimisation at huge scales. But for exploratory work, operational simplicity is important; a single formulation that reliably grows a variety of cells and is sufficiently forgiving of handling variation is valuable. → Adherence is a sticking point (hah, I amuse myself anyway). In most serum-free media systems, coating plates with adherence proteins is the standard. This is operationally annoying relative to culturing adherent cells with serum-containing media. (Let’s do something about this, why don’t we? 😉) |
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