Spin filter

Fig. 2. Schematic of a process for microcarrier perfusion culture using a spin filter device.

Leave to express for 3-4 days, then collect medium, spin, filter 0.22 pm, then go on to protein purification (method depends on the tags used etc.). 

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. 

As discussed above, fouling of the filter screen is a major concern regarding efficient operation of the spin-filter, because ideally perfusion processes should reliably operate for longer periods of time. Since replacement of internal units is practically impossible, the spin-filter should be designed and operated to avoid clogging, preventing a premature termination of the culture [18]. Dif-... 

Table 5. Overview of reported perfusion processes employing spin-filters as cell retention device... 

Fouling caused by increasing perfusion rates can be partially compensated by increasing the spin-filter rotation speed. However, according to Yabaimavar... 

Besides fouling, cell retention efficiency is another important factor regarding spin-filter performance. A poor retention capacity of a spin-filter leads to a low apparent growth rate of the cell culture due to cell leakage (Eq. 10). 

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

Yabannavar et al. [89] employed Eq. (11) to calculate the maximum perfusion flow rate attainable before cell wash-out, which occurs when cell growth is compensated by cell passage through the spin-filter or, according to Eq. (12), when Fapp = 0- Under these conditions ... 

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. 

Scale-up of spin-filters has been often studied in the recent years, and simple scale-up procedures have been proposed by Yabannavar et al. [81] and Deo et al. [13]. Yabannavar et al. [81] suggested a procedure based on keeping the ratio of permeation drag to lift force constant for the different production scales, in... 

Yabannavar et al. [81] proposed a proportionality relationship valid for spin-filters based on an analogy to Eq. (15). They defined the Reynolds number based on the tangential velocity at the screen surface. Since in spin-filters the permeation velocity, or perfusion flux, is given by Eq. (16), and it can be assumed that the screen porosity e will be maintained constant throughout the scale-up process, it is possible to write a proportionaHty relationship for the ratio from drag to lift force in spin-filters as given by Eq. (17). 

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) ... 

Although much progress has been made in the last decade regarding operation, design and scale-up of spin-filters, in most works found in the literature either fouling or retention problems (or both) were observed. A better comprehension of the fluid and particle dynamics involved in spin-filter perfusion would improve this situation. In this context, a valuable tool that could be used is computational fluid dynamics (CFD), which has been recently employed for the design and performance prediction of other cell separation devices [46,114]. 

Shen X, Sun L, Benassi E et al (2010) Spin filter effect of manganese phthalocyanine contacted with single-walled carbon nanotube electrodes. J Chem Phys 132 054703/ 1-054703/6... 

Szulczewski G, Tokuc H, Oguz K, Coey JMD (2009) Magnetoresistance in magnetic tunnel Junctions with an organic barrier and a MgO spin filter. Appl Phys Lett 95 202506... 

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... 

Filter the combined extracts (2.8 mL) through a 0.45-pm spin filter (Coming). 

Filter the final supernatant through a 0.22 pm spin filter (Spin-X, Corning). 

Widely known as perfusion, this operation mode presents the highest productivities and, at the same time, the highest operational complexity. Since the innovating work on a spin-filter in 1969 (Himmelfarb et al., 1969), the use of this operation mode has become more and more popular, both at laboratory and industrial scales (Chu and Robinson, 2001). 

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). 

Himmelfarb P, Thayer PS, Martin HE (1969), Spin filter culture the propagation of mammalian cells in suspension, Science 164 555-557. 

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