TFF & Bioprocessing
March 26, 2026 · Alphinity
In viral vector and cell therapy manufacturing, yield loss isn't a surprise. It's expected. Published data and internal process experience consistently point to 20–40% losses during tangential flow filtration (TFF). Teams track it. They try to optimize around it. They accept it as part of the process.
But there's a more important question: What if that loss isn't inevitable?
When yield drops during TFF, the investigation usually follows a familiar path:
All valid. All important. But rarely does the conversation go further upstream — to the mechanism moving the fluid through the system. The pump.
The industry often talks about "low shear" as a single concept. It isn't. Different pump technologies create fundamentally different fluid dynamics:
These differences matter — especially for fragile biologics. Because damage isn't just about flow rate. It's about how that flow is generated.
Every pass through a TFF loop exposes product to mechanical stress. In viral vector processes, this can lead to capsid damage, aggregation, or reduced transduction efficiency. In cell therapy, it can affect viability. For proteins, structural changes may impact function.
These effects are often grouped under "shear," but in many cases they are driven by how the fluid is handled at a mechanical level. This is where pump design becomes critical.
Technologies that minimize pulsation and avoid repeated high-stress zones create a fundamentally different environment for the product. Diaphragm-based systems designed to produce smooth, continuous flow can reduce pressure spikes and mechanical stress, helping preserve biologic integrity throughout the process.
Pressure behavior is another factor that is often underestimated. In many systems, pressure fluctuates throughout the process. This leads to inconsistent TMP, unstable flux, and increased membrane fouling. The result is not just reduced efficiency, but variability between runs.
By contrast, stable pressure profiles enable consistent filtration performance, improved reproducibility, and better product quality. This level of stability is not simply a control issue — it is a reflection of the underlying system design.
In early-stage development, every milliliter matters. Yet many TFF systems have high hold-up volumes, require larger starting material, and waste valuable product in the system.
This becomes critical in viral vector development, cell therapy processes, and early PD workflows. Low working volume isn't just a convenience — it's a yield strategy. And it's often overlooked when systems are designed around legacy architectures.
The reality is simple: modern biologics have evolved. The hardware used to process them largely hasn't. Traditional TFF platforms were not designed for AAV, lentivirus, CAR-T, exosomes, or LNPs — yet they are now expected to process them efficiently.
The result is a growing gap between what the biology needs and what the equipment delivers.
A new generation of TFF systems is emerging — built around:
Diaphragm-based systems using multi-diaphragm configurations can deliver smoother, low-pulsation flow — reducing pressure spikes and protecting sensitive molecules. Platforms designed with low internal volume and full drainability help maximize product recovery — particularly important in high-value biologics.
These are not incremental improvements. They represent a shift in how TFF systems are designed.
If your TFF step is losing yield… if your process behaves differently at scale… if your results are inconsistent run to run…
Then the question isn't: "How do we optimize this system?"
It's: "Is this system designed for the biology we're running?"
Learn More
Designed from the ground up for shear-sensitive biologics. Ultra-low working volumes, stable pressure, and PIXER® pump technology.