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| Cellular crossroads. New miniaturized hollow-fiber bioreactor. The insert illustrates the crosswise pattern of 17 oxygenation membrane (vertical) and 25 perfusion membrane (horizontal) hollow fibers in the cell compartment. (Biotechnol. Prog. 2001, 17, 828–831.) |
Typically, mammalian cell cultures are grown in monolayers in tissue culture plates, suspension flasks of growth media, or hollow-fiber bioreactors (first described in 1972). Bioreactors allow the diffusion of nutrients, gases, and waste products to and from cultured cells across special membranes while preventing necessary larger-molecular-weight growth factors from escaping.
Conventional bioreactor design is based on hemodialysis models, and hence,cell retrieval is inefficient and damaging to the cultures. Because such bioreactors have generally been used to maximize production of cells or secreted compounds, large-scale extracapillary volumes ranging from 2.6 to 50 mL are typical. But this standard setup makes it almost impossible to observe the living cells in place microscopically during growth and experimentation.
In a recent article (Biotechnol. Prog. 2001, 17, 828–831), Herma Gloeckner and Horst-Dieter Lemke of Acordis Research (Obernburg, Germany; www.membrana.de) detail the development and use of a miniaturized hollow-fiber bioreactor that allows visual inspection of cells through a microscope—the first such system, according to the authors. These miniature bioreactors use a cross-linked set of membranes (see the figure). This system allows researchers to follow cell growth and behavior during experimentation, whether to test the effect of drugs and physical changes or to optimize growth parameters.
Using the bioreactor, the scientists cultivated several leukemic cell lines. The growth of the cells was well controlled by adjusting the medium flow rate, and densities of up to 3.5 x 107/mL were obtained—without a change of medium or manipulation of cells. Because the system allows controlled growth in much more limited volumes (only 1 mL), it is ideal for “the cultivation of rare cell populations at high densities.” The ability to maintain high population densities in small volumes can be critical to the health of cells that require the exchange of limited amounts of growth factors for proper culture. For small cell numbers,the use of larger-volume bioreactors can result in too much dilution of these critical (and often poorly characterized) factors.
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