Every TFF conversation runs on the same handful of words. Flux, conversion, retention, diavolumes. Miss the exact meaning of any one of them and the discussion turns slippery: two people agree on a number while meaning different things by it. None of these terms is difficult on its own. The value is in using them precisely. Here is what each one actually measures.
Before the metrics, the streams they describe. A TFF step takes one flow and splits it into two. The feed enters the module. Whatever passes through the membrane is the permeate (or filtrate). Whatever is held back and recirculated is the retentate (or concentrate). Every number below is describing what is happening to one of these three.
Flux is the rate at which permeate crosses the membrane, normalized to the membrane area.
Flux (J) = permeate flow ÷ membrane area. Usually expressed in LMH, liters per square meter per hour.
Normalizing to area is what makes flux useful. A bench cassette and a production skid running at the same LMH are doing the same work per unit of membrane, which is how a process is scaled from one to the other. Flux is driven by transmembrane pressure, but only up to a point: past a certain pressure it flattens out, held back by the layer of retained material that builds at the membrane surface. That plateau is concentration polarization, and it is why more pressure stops buying more permeate.
Conversion is the fraction of the feed entering the module that leaves as permeate in a single pass.
Conversion = permeate flow ÷ feed flow, for one pass through the module, expressed as a percentage.
In a recirculating system, per-pass conversion is kept deliberately low, a few percent, and the target concentration is reached by looping the retentate around many times. In single-pass TFF the logic flips: conversion is the whole design, and the system is sized to reach the concentration you need in one trip. Push conversion too high in a single pass and the retentate concentrates so much against the membrane that polarization and fouling take over.
Retention, also called rejection, describes how completely the membrane holds a given molecule back.
Retention (R) = 1 − (permeate concentration ÷ retentate concentration). Its mirror image, the sieving coefficient S = 1 − R, is how freely a species passes into the permeate.
Retention is where yield and clearance live. You want your product fully retained, a retention near 1, so it stays in the retentate and is not lost to permeate. You want the impurities you are removing to have low retention, high sieving, so they pass through and wash away. A membrane is chosen so those two numbers sit far enough apart to separate the product from what you want gone.
Diafiltration removes small molecules, such as salts, buffer components, or free payload, by adding fresh buffer while permeate leaves and the retentate volume is held constant. A diavolume is one retentate volume of buffer exchanged in that way.
After N diavolumes, a freely permeating solute falls as C / C₀ = e−N (for a sieving coefficient near 1). The washout is exponential.
Because it is exponential, the diavolume count tells you directly how clean you will get: roughly 3 diavolumes removes about 95%, 5 removes about 99%, and 7 removes about 99.9% of a fully permeable species. It also explains why chasing the last fraction is expensive: each additional log of clearance costs roughly the same two to three diavolumes of buffer again.
Where Alphinity fits: these numbers only mean something if they hold steady. The TFFi™ system controls transmembrane pressure and crossflow precisely, so flux, conversion, and diavolume counts stay reproducible run to run. Because it is membrane-agnostic, the retention you characterize is the retention you keep.
| Term | What it measures | Expressed as |
|---|---|---|
| Flux | Permeate rate per unit of membrane area | LMH (L/m²/h) |
| Conversion | Permeate as a fraction of feed, per pass | Percentage |
| Retention | How completely a molecule is held back | 0 to 1 (or %) |
| Diavolumes | Buffer volumes exchanged in diafiltration | A count (often 5 to 7) |
Get the vocabulary exact and the rest of the conversation follows. Flux is a rate, conversion is a ratio per pass, retention is a separation, and a diavolume is a unit of washing. Four words, and most of what happens on a TFF skid is described by them.
Flux is the permeate flow rate per unit of membrane area, usually expressed in liters per square meter per hour (LMH). It measures how fast permeate passes through the membrane, normalized to area so the number holds as the process scales.
Conversion is the fraction of the feed entering the module that leaves as permeate in a single pass, expressed as a percentage. It sets how much concentration you achieve per pass, and pushed too high it drives concentration polarization at the membrane surface.
Retention describes how completely the membrane holds a molecule back: R equals 1 minus the ratio of permeate to retentate concentration. A retention near 1 keeps product in the retentate, which protects yield. The sieving coefficient, 1 minus retention, describes how freely a species passes into permeate, which sets clearance of impurities.
A diavolume is one retentate volume of fresh buffer exchanged during constant-volume diafiltration. Removal of a freely permeating solute is exponential, so roughly 3 diavolumes clears about 95 percent, 5 clears about 99 percent, and 7 clears about 99.9 percent.
Crossflow, transmembrane pressure, concentration, and diafiltration. The essentials of TFF explained simply, with visuals.
Why permeate flux plateaus regardless of pressure, and what the polarization layer is doing at the membrane surface.
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