At a glance
Diafiltration
Scope1-100 kDa MWCO
CAPEX$80k-$500k
Best forBuffer exchange, salt removal
vs
Size Exclusion Chromatography
ScopeSize-based
CAPEX$150k-$1M
Best forBuffer exchange, aggregate removal
Decision criteria
| Criterion | Diafiltration | Size Exclusion Chromatography | Verdict |
|---|---|---|---|
| Separation principle | Buffer exchange, salt removal | Buffer exchange, aggregate removal | Constant-volume membrane wash vs gel filtration |
| Throughput / scale | 100-50,000 L/hr | 1-100 L/hr | DF much higher |
| Capital cost | $80k-$500k | $150k-$1M | DF lower |
| Operating cost | Wash water | Resin life + dilution | DF much cheaper |
| Product purity ceiling | Buffer exchange | Resolves close MW | Application-dependent |
Quick verdict
DF is the manufacturing buffer-exchange tool. SEC is the analytical one.
Rule of thumb: Above ~1 L batch? DF. Below or analytical? SEC.
Frequently Asked Questions
When should I choose Diafiltration over Size Exclusion Chromatography?
Use diafiltration for production-scale buffer exchange — concentrate first, then exchange. Standard final formulation step.
When should I choose Size Exclusion Chromatography over Diafiltration?
Use SEC for very small batches or where dilution is acceptable and you need to resolve closely-sized species.
Can these two techniques be used together?
Almost never in series. DF replaces SEC for production buffer exchange.
Which has lower OPEX at scale?
DF costs scale with wash water (5-10 diavolumes). SEC costs scale with resin life and dilution-driven downstream.
Read more on each technique
Try both in your flowsheet
Build a process with each option side by side and compare yield, purity, and cost.
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