Acoustic Wave Separation as an Alternative to TFF

An acoustic wave-based technology for cell harvesting applications may help enable continuous manufacturing.
Sep 01, 2017
Volume 30, Issue 9, pg 30

Acoustic wave separation (AWS) technology for cell harvesting and clarification, unlike tangential-flow filtration (TFF), does not achieve separation of cells using a physical barrier, but with high-frequency resonant ultrasonic waves. The cells are held back using an acoustic force field as the bioprocess fluid flows through an open channel. The use of acoustic waves allows differentiation of particles of equal size, and thus the technology can be used for the separation of particles from the nano (20 nm) to macro (5-400 µm) scales. The process is gentle; cells are subjected to extremely low shear forces unlike in TFF and centrifugation, and thus cell viability is not impacted, according to Chris Leidel, vice-president of business development with FloDesign Solutions (FDS). 

Equally important, there is no potential for clogging or fouling in the open chamber, and thus no need to halt operation and change the membrane filter. “One-hundred percent product transmission can be maintained for long periods, and because all product is removed throughout the run, it is not concentrated in the reactor overtime, potentially leading to product quality and consistency improvements. Furthermore, fines are not returned to the bioreactor, leading to cleaner culture conditions, and the tunability of the acoustic waves means that the clarification conditions can be adjusted to meet the specific needs for each cell culture process,” Leidel says. Overall, he adds, these attributes make AWS a more selective and robust alternative process to TFF and normal-flow filtration (NFF), and may translate into potentially cleaner reactions, more productive cells, and better process economics.

Pall Life Sciences has exclusively licensed the FDS AWS technology for continuous clarification of perfusion processes in biomanufacturing (branded as the Cadence Acoustic Separator), and the two companies are working closely to further develop the technology. For perfusion, Leidel expects a process-development-scale system to be introduced early in 2018 with a commercial-scale version (50-500 L) to reach the market shortly thereafter.

Applikon Biotechnology also offers an ultrasound-based solution to the biopharmaceutical industry, the BioSep acoustic perfusion system based on Sonosep Technology. Five models cover capacities ranging from 1-1000 L/day, according to the company’s website (1).

Adoption hurdles

The biggest challenge in getting the acoustic wave separation technology accepted in the biopharmaceutical industry will be the fact that TFF is already proven and companies are comfortable with it, according to Leidel. He also notes that because some fines come through the system, a small secondary filtration step is needed. AWS devices must also scale with the size of the bioreactor, which FDA and Pall are currently addressing. There is, in addition, a theoretical cell density limit, but to date the companies have been successful with cultures up to 100 million cells, according to Leidel.

“Otherwise, the AWS consumables are single-use, gamma-irradiated, closed systems like current TFF devices with similar pumps and setup requirements. We also have extensive data from a number of long-term runs performed in conjunction with different customers demonstrating similar and in some cases improved results in terms of impact on cell growth, cell viabilities, product expression, and other attributes indicative of cell-culture performance, are achieved with both technologies,” Leidel states.

The rate of adoption of acoustic separation technology for continuous harvesting will, according to Leidel, depend largely on the rate of adoption of continuous processing. “There is definitely growing recognition of the benefits of continuous manufacturing. We are seeing an increasing interest from industry leaders to work with equipment vendors like Pall to develop effective solutions that will enable integrated continuous bioprocessing. As a result, I don’t think the timeframe for adoption of acoustic separation and other technologies that facilitate continuous manufacturing will be too long,” Leidel concludes.

It should also be noted that AWS technology is applicable for perfusion production of cell, gene, and viral vector therapies. “AWS provides a gentle means for harvesting cells. The challenge is to scale down the technology for these personalized medicines,” Leidel observes. FDS is focused on developing solutions for this segment of the biopharma market, which was not part of the license to Pall.


1. Applikon Biotechnology, “BioSep Acoustic Perfusion System,”

Article Details

BioPharm International
Volume 30, Number 9
September 2017
Page: 30


When referring to this article, please cite it as C. Challener, “Acoustic Wave Separation as an Alternative to TFF," BioPharm International 30 (9) 2017.

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