Why is Membrane Chromatography Faster Than Resin Chromatography?
Convection vs. Diffusion
Imagine a glass holding sugar. After adding water, it is left to sit. Ultimately, the sugar will dissolve after a few hours. This is an example of a diffusion dominant process. On the other hand, If the sugar and water are stirred, dissolving will be completed in minutes. This is an example of a convection dominated process. This simple but effective example demonstrates how a convection-based process is much faster than that of diffusion.
Resin vs. Membrane Chromatography
For several decades, resin-based chromatography columns, consisting of porous resin beads, have been used as a workhorse in biologics purification. The internal porous channels provide resin particles very large, specific surface area for biologics binding. However, target molecules must travel into the channel and access to the binding sites through a diffusion-based mechanism. Consequently, resin columns usually require a very long residence time, hindering the productivity of biologics purification. Additionally, the pore size in resin columns is generally below 100 nm. Thus, the issue of inadequate productivity becomes more significant with larger gene products, including mRNA, plasmid DNA, AAV and LV vectors.
Conversely, the straight-through pores present in membranes allow for purification to be completed through a convection dominated process. As an advantage of this design, membranes can operate at very short residence times. Additionally, with large biologics, there are minimal size exclusion effects on membrane applications. With a pore size generally between 100 nm and a few micron meters, the membrane can have a much higher binding capacity and flow rate for gene therapy products when compared to resins.
Size Comparison: Biologics vs. Pores
Unlike resin bead purification products, the open, straight-through pores in membrane chromatography technology accommodates a wide size range of biologics. For example, a commonly used resin product pore size is usually in the sub-100 nm range. In the case of plasmid DNA purification, a biologic with sizes between 150 and 300 nm, the smaller resin pores cannot satisfy this larger target molecule at a high binding capacity. On the other hand, the Purexa™ product line has pore sizes ranging from 0.3µm to 5 µm. With a much larger pore size, the target molecule is easily able to bind to the membrane at a high capacity, regardless of the size. Thus, Purilogics’ membrane chromatography products can be applied for the purification of many sizes of biologics while also maintaining and a rapid flow rate and high binding capacity. Figure 2: Size Comparison: Biologics vs. Pores compares the sizes of these common biologics to the sizes of both resin and membrane pores.
Common biologics that Purilogics’ membranes can purify include, but are not limited to:
Monoclonal Antibody
mRNA
Adeno-associated virus (AAV)
Lentivirus/Lentiviral vectors (LV)
Plasmid DNA
Oligo nucleotides; Nucleotides/Nucleosides
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