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Related Experiment Video

Updated: Jun 8, 2025

Tangential Flow Ultrafiltration: A “Green” Method for the Size Selection and Concentration of Colloidal Silver Nanoparticles

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Published on: October 4, 2012

An Experimental and Modeling Approach to Study Tangential Flow Filtration Performance for mRNA Drug Substance

Ehsan Nourafkan¹, Charlotte Kenyon¹, Adithya Nair¹

¹Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK.

Biotechnology Journal

|November 8, 2024

Summary

Tangential flow filtration (TFF) effectively purifies messenger RNA (mRNA) from in vitro transcription (IVT) mixtures. This validated fouling model optimizes mRNA separation, ensuring high recovery and purity for next-generation vaccines and therapeutics.

Keywords:

Hermia model mRNA separation membrane fouling tangential flow filtration transmembrane pressure

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Area of Science:

Biotechnology
Bioprocessing
Filtration Technology

Background:

The COVID-19 pandemic accelerated mRNA manufacturing development for vaccines and therapeutics.
Efficient purification of mRNA from in vitro transcription (IVT) reaction mixtures is critical for producing high-quality mRNA products.

Purpose of the Study:

To evaluate tangential flow filtration (TFF) for high-recovery, high-purity mRNA separation from unreacted nucleoside triphosphates (NTPs).
To validate a fouling model using experimental TFF data to describe mRNA adsorption onto filtration membranes.

Main Methods:

Tangential flow filtration (TFF) was employed for mRNA purification.
A fouling model was developed and validated against experimental TFF data.
Optimization of capacity load, transmembrane pressure (TMP), and feed flux was performed.

Main Results:

Achieved over 70% mRNA recovery without degradation.
Successfully validated a fouling model for mRNA adsorption on filtration membranes.
Identified optimal TFF parameters: capacity load of ~19 g/m², TMP <2.5 psi, and feed flux of 300 LMH.

Conclusions:

TFF is a viable method for high-purity mRNA separation from IVT mixtures.
The validated fouling model aids in process monitoring, filter maintenance, and cost reduction.
This purification approach supports the development of diverse mRNA therapeutics for various diseases.