“Evolutionary downstream improvements have not kept up with protein titers from cell cultures.”
-Dr. Thierry Ziegler, Genetic Engineering and Biotechnology News (Vol. 32, No. 11)
Bioprocess operators have been facing a growing problem with of upstream cell culture and fermentation productivity outpacing downstream purification abilities. Over the years, improvements in downstream process technology, mostly increases in resin binding capacities, have been insufficient to equal the pace of improvements in upstream operations. Operators have been resorting to installing parallel downstream production trains, including additional columns and buffer preparation and storage systems.
Aroostook Pure is concerned with the inefficiency of approaches of this sort, and is developing the Aroostook Loop technology to be the revolutionary improvement that today’s large scale Bioprocess facilities desperately need.
By cycling resin, the Bioprocess Aroostook Loop achieves numerous advantages over traditional chromatography and other mass transfer based technologies. The most influential of which is a reduction in consumables, including resin and buffers. The reduced resin usage (Up to 70%) translates in to a smaller resin inventory, resulting in smaller storage requirements. Reduced buffer usage means a smaller water demand, as well as smaller buffer hold vessels, which in turn, reduce the physical foot print of the downstream process area.
The Aroostook Loop is not constrained by the binding capacity of the resin; rather, its recycling feature allows operators to process entire batches with higher than expected titers by extending the operating time of the loop while using a drastically smaller amount of resin.
The Bioprocess Aroostook Loop can also eliminate the post-harvest clarification. Because of the resin bed undergoes a partial fluidization; particulate contaminants are trapped by the bed and then washed away during resin cycling. This filtration mechanism eliminates the need for a post-harvest filtration step to remove cellular debris.
This elimination of the post-harvest clarification places the Aroostook loop in a distinct advantage over simulated moving bed, (SMB). However, by eliminating the need to pack multiple columns, considerable time and effort are also saved. Production workers simply load the resin into the loop, connect process fluids, and standardize probes.
Process development for the Aroostook Loop is simple and straight forward since it follows the same load, wash, elute, and regeneration methodology. A process developed for a chromatographic unit operation can be transferred directly into an Aroostook Loop using the same resin, buffers and linear flow rates, only in lower quantities.
For 1500-2000 litre scale processes, the Bioprocess Aroostook Loop will be supplied in either a non-disposable or a disposable version which can serve as the initial capture step. The non-disposable version can be completely disassembled and cleaned in a standard glass washer and autoclaved/ depyrogenated if required. The disposable version will be the only purification system that can be used as an initial capture step and then be disposed of entirely, avoiding cleaning validation requirements. In both cases, the buffer requirements may be reduced to the point where disposable bags may be used instead of permanent storage vessels, further reducing validation costs.
These features make the Bioprocess Aroostook Loop the revolutionary leap forward the bioprocess industry needs in its downstream process operations. Its compact size and potential disposability make it an operationally and economically effective replacement for traditional chromatography. Bringing downstream costs down.