Spin filter bioreactor

Jo EC, Yun JW, Jung KH, Chung SI, Kim JH (1998), Performance study of perfusion cultures for the production of single-chain urokinase-type plasminogen activator (scu-PA) in a 2.5-L spin-filter bioreactor, Bioproc. Eng. 19 363-372. 

Fig. 4. Two spin-filter bioreactors configured in series for the growth of embryogenic cells and the promotion of somatic embryo maturation on a large scale. The stage 1 bioreactor is for cell proliferation and operates on a continuous culture mode the stage 2 bioreactor is for somatic embryo maturation and operates in a perfusion mode...

Himmelfarb et al. [80] introduced spin-filters as a cell retention device for high cell density perfusion cultivations of mammalian cells in suspension. Spin-filters are cylinders with a porous wall, which are placed inside stirred tank bioreactors, either mounted on the impeller shaft or driven by an independent motor (Fig. 5). Perfusate is pumped out from inside the spin-filter at the same... 

Fig. 5. Schematic view of a spin-filter mounted on the impeller shaft of a bioreactor. Alternatively, spin-filters can be driven by an independent motor...

In a spin-filter based stirred bioreactor, there are various forces acting on both the liquid medium and the cell particles gravity force, axial force due to impeller rotation, centrifugal force created by the spin-filter rotation, and radial force (drag) generated by the perfusion flux. 

For a spin-filter based bioreactor, an overall cell balance as given by Eq. (11) can be applied [89] ... 

As a consequence, the perfusion bioreactor can only be operated up to a cell concentration supported by the perfusion rate In this way, spin-filter retention efficiency determines the maximum attainable cell concentration in a given perfusion process. 

Yabannavar et al. [81] used Eqs. (19) and (20) for scale-up purposes. Based on successful operation conditions determined for an existing 12-L bioreactor, they calculated the spin-filter dimensions and operation conditions for an existing 175-L bioreactor. Experiments with the spin-filter designed for the large-scale bioreactor resulted in an absence of filter clogging with cell retention efficiency similar to the 12-L bioreactor. This was considered as an evidence that the suggested scale-up strategy is adequate. 

Deo et al. [13] proposed an empirical model based on experimental results obtained with a small-scale spin-filter based bioreactor. They observed that the perfusion flux capacity, which was defined as the perfusion flux at which fouling begun to occur, was proportional to the inverse of the cell concentration and to the square of the tangential velocity at the screen surface (Eq. 21) ... 

Deo YM, Mahadevan MD, Fuchs R. Practical considerations in operation and scale-up of spin-filter based bioreactors for monoclonal antibody production. Biotechnol Prog 1996 12 57-64. 

Batch cultivation is perhaps the simplest way to operate a fermentor or bioreactor. It is easy to scale up, easy to operate, quick to turn around, and reliable for scale-up. Batch sizes of 15,000 L have been reported for animal cell cultivation [2], and vessels of over 100,000 L for fermentation are also available. Continuous processes can be classified into cell retention and non-cell retention. The devices typically used for cell retention are spin filters, hollow fibers, and decanters. Large-scale operation of continuous processes can reach up to 2,000 L of bioreactor volume. Typically, the process is operated at 1-2 bioreactor volumes... 

When bioreactors coupled to cell retention devices are used, it is also necessary to evaluate the scale-up of the cell separation equipment. In the case of the spin-filter (see Chapter 11), parameters such as filter rotation velocity and the ratio of filtration area to bioreactor working volume are particularly relevant (Deo et at, 1996). 

Schematic representation of a spin-filter fitted on the impeller shaft of a bioreactor.

The internal spin-filter consists of a cylinder with porous walls (normally a mesh), which rotates inside a bioreactor. It may be driven by an independent motor or may be fitted on the impeller shaft (Figure 11.14). Culture medium is continuously removed through the mesh, under vacuum, while fresh medium is added at the same volumetric rate to the bioreactor. 

Mesh fouling is the main problem associated with the operation of a spin-filter. As it is located inside the bioreactor vessel, it is impossible to exchange the filter under sterile conditions once it has clogged. When this happens, the culture must be terminated. 

Figueredo-Cardero A, Chico E, Castilho LR, Medronho RA (in press), CFD study of the fluid and particle dynamics in a spin-filter perfusion bioreactor, In Hauser H (Ed.), Proceedings of the 20th ESACT Meeting (European Society for Animal Cell Technology), Springer, Dordrecht. 

Until now, bioreactors of various types have been developed. These include loop-fluidized bed [14], spin filter, continuously stirred turbine, hollow fiber, stirred tank, airlift, rotating drum, and photo bioreactors [1]. Bioreactor modifications include the substitution of a marine impeller in place of a flat-bladed turbine, and the use of a single, large, flat paddle or blade, and a newly designed membrane stirrer for bubble-free aeration [13, 15-18]. Kim et al. [19] developed a hybrid reactor with a cell-lift impeller and a sintered stainless steel sparger for Thalictrum rugosum cell cultures, and cell densities of up to 31 g L1 were obtained by perfusion without any problems with mixing or loss of cell viability the specific berberine productivity was comparable to that in shake flasks. Su and Humphrey [20] conducted a perfusion cultivation in a stirred tank bio-... 

Fig. 1. Different types of bioreactors for plant cell, tissue and organs. (A) mechanically-agitated bioreactors, a aeration-agitation, b rotating drum, c spin filter. (B) air-driven bioreactors, a bubble column, b draft tube, c external loop, (C) non-agitated bioreactors, a gaseous phase (mist), b oxygen permeable membrane aerator, c surface aeration, (D) light emitting draft tube...

Fig. 6 Various types of animal cell bioreactors (A) roller bottle (B) rotating disk (C) stirred tank with a marine impeller (D) tank with a pulsating agitator (E) stirred tank with a spin filter (F) airlift (G) fluidized bed and (H) hollow fiber. (View this art in color at WWW. dekker. com.)...

Figure 18. Different types of bioreactors for plant cells, tissues and organs. (A) Shake Flask. (B) Aeration-Agitation. (C) Percolated Impeller. (D) Draught Tube Air-lift. (E) Draft Tube with Kaplan Turbine. -Air-liftloop. (Gj Rotating Drum. (7/1 Light Emitting Draught Tube. (I) Spin Filter. (J) Bubble Column. (K) Aeration. (L) Gaseous Phase.

Yabannavar VM, Singh V, Connelly NV. (1992) Mammalian cell retention in a spin filter perfusion bioreactor. Biotechnol. Bioeng., 40 925-933. 

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