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A diffusion cell is, in laboratory work, an apparatus that holds a membrane (often excised skin or a synthetic film) between a donor compartment and a receptor compartment so that the rate at which a substance crosses the membrane can be measured. The same words are also searched for the biology topic, diffusion in cells, which is covered below.
Short answer
As an apparatus, a diffusion cell separates a donor compartment (where the formulation is applied) from a receptor compartment (where the permeated substance is sampled), with the membrane between them. The best-known design is the vertical Franz cell. In cell biology, diffusion is the passive, energy-free movement of solutes down a concentration gradient across a membrane.
Definition and scope
Two unrelated meanings share the phrase, and they need separating before anything else.
- Apparatus sense (lab equipment). A diffusion cell is a permeation-testing device. Common families include the vertical Franz cell, side-by-side cells and in-line (flow-through) cells; the manufacturer PermeGear, for example, lists all three, in jacketed or unjacketed configurations, and describes the measurements as diffusion coefficients, partition coefficients and membrane permeabilities.
- Biology sense. Diffusion across cell membranes: simple diffusion and facilitated diffusion (see the questions further down).
This page is general information for researchers and laboratory staff. It is not a protocol and does not replace a validated method or a regulator’s guidance.
What is a Franz diffusion cell?
A Franz cell is a vertical diffusion cell developed by Dr Thomas Franz and described in 1975 (Franz TJ, J Invest Dermatol 64:190-5) to examine percutaneous absorption in vitro and to correlate it with in vivo results. According to a 2024 review by Lane in the European Journal of Pharmaceutical Sciences, earlier horizontal designs are rarely used today. The formulation is applied to the donor compartment, the receptor compartment normally holds an aqueous medium, and the skin sits between the two. The receptor medium is agitated, usually with a magnetic stirring bar in a stand-alone cell.
How a diffusion cell is used in practice
The two main set-ups are static (stand-alone) cells and flow-through cells. OECD Test Guideline 428 (Skin Absorption: In Vitro Method, adopted 13 April 2004) states that both are acceptable. In a static system the receptor fluid should be continuously stirred and sampled regularly; in a flow-through system the flow rate must not hinder diffusion into the receptor fluid. The guideline also calls for good temperature control of the cell and its contents, with humidity preferably between 30 and 70%.
Static (Franz) versus flow-through cells
| Feature | Static / stand-alone (Franz) cell | Flow-through cell |
|---|---|---|
| Receptor mixing | Stirring, usually a magnetic bar (Lane 2024); OECD 428: continuously stirred | Continuous replacement of the receptor medium (Lane 2024) |
| Sampling | Manual sampling for a stand-alone cell; cell arrays can automate collection (Lane 2024) | Automated sample collection is possible (Lane 2024) |
| Keeping sink conditions | May need optimised sampling times and volumes for poorly soluble actives (Lane 2024) | Easier, because the medium is continuously replaced (Lane 2024) |
| OECD 428 status | Acceptable | Acceptable; flow rate must not hinder diffusion |
Sink conditions and sampling: a checklist of what the sources say
- Sink. The receptor must not hinder absorption (OECD 2004). Lane (2024), citing Skelly (1987), describes sink as the thermodynamic activity of the active in the receptor not exceeding 10% of that in the donor.
- Receptor medium. Phosphate-buffered saline at pH 7.4 is acceptable if the active is soluble enough. For poorly soluble actives, additives such as bovine serum albumin or a non-ionic surfactant (PEG-20 oleyl ether) have been reported. The medium should be deaerated to avoid bubbles.
- Alcohols. Ethanol and isopropanol have been used, but ethanol may compromise the skin barrier. The FDA draft IVPT guidance (2022) states that including organic solvents and alcohols in the receptor solution is not recommended and may invalidate the IVPT method.
- Sampling volume. Each sampled volume is replaced with an equal volume of fresh receptor solution to maintain sink. Too large a volume dilutes the sample; too small or too infrequent lets the active accumulate and sink is lost. Lane advises pilot experiments for unknown actives.
- Bubbles. Air bubbles under the skin must be avoided when sampling.
- Reference substances and integrity. OECD 428 mentions reference substances (for example caffeine, benzoic acid, testosterone) to check a range of lipophilicity, and evidence of barrier integrity when skin has been stored. If metabolism is being studied, the receptor fluid must support skin viability.
Infinite dose versus finite dose
An infinite dose is a large amount that gives a steady-state profile; it is used for permeation enhancers or new actives but is not representative of in vivo use. A finite dose is a small amount (Lane gives 2 to 10 µl/cm² as typical), usually applied unoccluded, so the donor depletes. Lane emphasises mass balance (skin deposition, retention and permeated amount), and notes that an EMA draft guideline requires skin deposition and distribution to be reported.
Where it matters for labs and supply decisions
Diffusion cells appear wherever skin delivery or membrane permeation has to be measured in vitro, as in OECD 428 skin absorption work and in-vitro permeation testing (IVPT) of topical products. Variants exist for nail and scalp tissue, and 3D-printed Franz cells have been reported (Sil et al. 2018, cited by Lane). Because the cell design, receptor medium and dose type all change the result, a method description should record them. Related permeation work on this site includes the Caco-2 permeability assay (a cell-monolayer system), glove breakthrough time and permeation data, and iontophoresis.
Common misunderstandings
- “A diffusion cell is a biological cell.” In the apparatus sense it is a device, not a cell. The two meanings share only the word diffusion.
- “Any receptor liquid will do.” The receptor has to maintain sink; the sources above single out alcohols as a particular concern.
- “Infinite dose mimics real use.” Lane states it is not representative of in vivo exposure; finite dose is closer.
- “Agar disk diffusion is the same thing.” The Kirby-Bauer disk diffusion test measures antimicrobial inhibition zones on agar, which is a different method.
Frequently asked questions
What is a Franz diffusion cell?
A vertical diffusion cell, introduced by Thomas Franz in 1975, in which a membrane such as skin separates a donor compartment holding the formulation from a stirred receptor compartment that is sampled over time to measure permeation.
Why is diffusion in cells important?
Stillwell (2016, An Introduction to Biological Membranes) notes that life depends on a membrane’s ability to control solute levels in the compartments it separates, and that the diffusion rate of a solute is essentially fixed, which limits cell size and sets a theoretical limit for enzymatic reaction rate.
Can you give examples of diffusion?
Oxygen crossing a membrane is the standard example of simple diffusion; glucose entering cells through GLUT transporters is an example of facilitated diffusion. In the laboratory, a drug permeating skin in a Franz cell is an example of measured diffusion across a membrane.
What are the key differences between simple and facilitated diffusion?
| Property | Simple diffusion | Facilitated diffusion |
|---|---|---|
| Energy | Passive, no energy input | Passive, no additional energy required |
| Driving force | The solute’s own concentration gradient | The solute’s own concentration gradient |
| Protein needed | No; can occur anywhere in the bilayer | Yes; a specific transmembrane protein or carrier |
| Kinetics | No saturation described | Michaelis-Menten saturation kinetics |
| Specificity | Limited to water, small uncharged solutes and gases | Highly specific; can distinguish d-glucose from l-glucose |
| Speed | Slower | Orders of magnitude faster than simple passive diffusion |
These rows are from Stillwell (2016). Sodium-coupled glucose uptake is a separate, active process and is not facilitated diffusion.
Sources
- Lane ME. In vitro permeation testing for the evaluation of drug delivery to the skin. Eur J Pharm Sci. 2024. doi:10.1016/j.ejps.2024.106873 (read 2026-11-07).
- OECD. Test Guideline 428: Skin Absorption: In Vitro Method, adopted 13 April 2004 (read 2026-11-07).
- Franz TJ. J Invest Dermatol. 1975;64:190-5.
- Stillwell W. Membrane Transport. In: An Introduction to Biological Membranes. Elsevier; 2016. PMC7182109 (read 2026-11-07).
- PermeGear, diffusion testing fundamentals (cell family naming only; read 2026-11-07).
