Jim Simmons is the Senior Director of Education at SpectrumLabs.com. He has over 30 years experience in membrane separations and spent 15 years as the Regional Sales Manager for the central United States. Jim now conducts the Spectrum Lab’s Training and Education Program.

In this installment, we address the two main TFF platforms: flat membrane and hollow fiber membrane. Each has advantages and disadvantages, and we aim to provide insight and understanding to the platforms.

Both geometries have been around since the early days of TFF, but limitations of membrane materials early on led to flat membrane becoming more widely recognized in bioseparation applications.

Flat Sheet TFF

Devices that hold flat membranes for TFF are generally known as cassettes. Disk-shaped flat membranes are also used as dead-end filters, and flat membrane is also ‘jelly rolled’ into spiral wound filters used in industrial processes.


The support substrate eliminates the need for strength characteristics in the membrane, allowing for a thin membrane wall and compatibility with a wide variety of membrane (media) chemistries.

A membrane layer consists of three main components: the membrane, a support substrate, and a channel spacer. A device is made by stacking these layers together.

A membrane layer consists of three main components: the membrane, a support substrate, and a channel spacer. A device is made by stacking these layers together.

During TFF, the sample flows through the channel, which is controlled by the size of the channel spacer.  As the process fluid passes through the channel a way must be found to evenly disperse the sample across the membrane surface.  To this end, baffles are often used in the channel spacer to disperse the liquid flow.  In TFF, the baffles can lead to a turbulent flow condition within the channel, making it difficult to accurately measure critical operating variables.  This makes it difficult to design processes with precise reproducibility.  Some flat membranes are available without baffles; however, then even dispersion of the sample over the membrane surface becomes an issue.  Scaling up processes to production level using flat membrane can be difficult as it is not possible to reproduce design parameters with precision as surface area increases.

The principal advantages and disadvantages of flat membrane are:

  • A support substrate allows for the use of a wide variety of media chemistries and a thinner membrane wall.
  • Turbulence in the channel limits precise measurement of operating conditions, inhibiting process design options.
  • Scale up can be complicated.
  • Cost and design restrict options for single-use (validated) applications.
Hollow Fiber TFF

Hollow fiber membrane is made via an extrusion process.  This results in a membrane shaped like a soda straw, with the inside of the straw (the lumen of the fiber) serving as the channel through which the sample passes.  The membrane wall is self-supporting, with no support substrate layer, making membrane wall strength vitally important and often leads to a thicker membrane wall.

In the past, fewer media chemistries were available that offered the right combination of strength and performance, resulting in limited offerings.


The sample fluid passes through a hollow fiber membrane channel in a laminar, not turbulent manner, resulting in uniform sample and pressure distribution throughout the channel.  This allows for precise measurement and control of critical operating parameters greatly enhancing the ability to design a process with precise repeatability.  Channel dimension is easily varied to suit the needs of the application.

The principal advantages and disadvantages of hollow fiber are:

  • The hollow fiber extrusion process eliminates the support substrate layer, requiring self-supporting membrane and a thicker membrane wall.
  • Today’s membrane media meets the needs for strength and separation performance.
  • Hollow fiber allows for direct measurement of critical operating conditions, enhancing process-design robustness.
  • In general, TFF using hollow fiber is more gentle for the sample.
  • A generally lower cost provides options for single use (validated) applications with hollow fiber.

Hollow fiber membrane is assembled into devices commonly known as modules. Recent developments in media chemistries means applications for hollow fiber are no longer restricted by limited media choices.


In the next installment, we will discuss various media chemistries and their relative advantages and disadvantages in TFF applications.