Among the various filtration methods available, normal flow filtration (NFF) and tangential flow filtration (TFF) are two commonly used methods in clarification and separation for both upstream and downstream processing in the biopharmaceuticals manufacturing process. In this article, we will explain the differences between TFF and NFF, and their respective advantages and disadvantages.

Table of Contents

1. Understand Normal Flow Filtration
   1. Advantages
   2. Disadvantages
2. Understand Tangential Flow Filtration
   1. Advantage
   1. No Filter Cake
   2. Gentle Separation
   3. Concentration and Diafiltration
   4. Linearly Scale-up
   5. Reusable
   2. Disadvantages
3. Conclusion

Understand Normal Flow Filtration

Normal flow filtration (also known as dead-end filtration), is a conventional filtration method that solutions flow vertically through the membrane. Molecules bigger than membrane pores retain and smaller molecules pass through.

Advantages:

Normal flow filtration are widely used in various industries for many years, which makes it easier to find suitable filters and membranes.The normal flow filtration system is straightforward and easy to set up than TFF system. 

Disadvantages:

However, normal flow filtration has a drawback that macromolecules tend to accumulate on the membrane surface, forming a layer known as a filter cake. As filtration time increases, this layer gets thicker, leading to reduced filtration efficiency and a shorter lifespan of the membrane.

Learn more about Cobetter Normal Flow Filtration Filters.

Understand Tangential Flow Filtration

In tangential flow filtration, the fluid flows tangentially across the membrane surface and the transmembrane pressure difference created by the fluid presses a portion of the solution against the filter membrane, while the retained portion circulates back through the system.

Advantages：

1. No filter cake

In tangential flow filtrations, the sample flows and rinses the membrane surface which prevents the accumulation of macromolecules and minimizes concentration polarization from reduced flow rate. So, it ensures a consistent flow rate and significantly extends the lifespan of the filter membrane. Furthermore, the transmembrane pressure is determined and maintained, allowing a large volume to be processed using an optimal membrane surface area.

2. Gentle Separation:

TFF operates at low transmembrane pressure, which ensures gentle separation and minimal shear stress on sensitive biomolecules. The shear rate can be accurately regulated by modifying the feed flow rate. 

3. Concentration and Diafiltration

Furthermore, the permeate that passes through the membrane is collected, while the remaining liquid is recycled and concentrated, which makes it possible to exchange buffers (diafiltration) during tangential flow filtration.

4. Linearly Scale-up

Last, TFF systems are modular in nature, allowing for flexibility in increasing the filtration area by adding more modules or increasing the length(hollow fiber modules). For this reason, most TFF devices are linearly scalable.

5. Reusable

With proper cleaning and storage, TFF devices can be reused, which significantly reduces consumable costs than normal flow filtration.

Disadvantages:

Complexity: To achieve optimal performance, it is essential to fine-tune operating conditions, including transmembrane pressure, cross-flow velocity, and temperature, etc.

Therefore, TFF systems can be more complex to set up and operate compared to normal flow filtration, requiring additional equipment such as holders, pumps, pressure sensors, and incurring the cost of implementing robust control systems to uphold ideal operating conditions. Which will lead to a higher initial investment cost as well.

Learn more about Cobetter Tangential Flow Filtration Cassettes.

Cobetter Hollow Fiber Filters

Conclusion

Normal flow filtration is known for its simplicity and well-established. Which is used when there is a need for clarification or bio-burden reduction of low-solid solutions, or sterile filtration in final polishing steps.

While tangential flow filtration has advantages in less chance of filter clogging, gentle filtration, concentration and diafiltration capabilities, linearly scalable and reusable, which is suitable for high-solid and viscous solutions. All the benefits of TFF make it becoming the preferable separation method in biotechnology fields.