Chemistry: molecular biology and microbiology – Apparatus – Mutation or genetic engineering apparatus
Patent
1991-02-22
1993-12-14
Wityshyn, Michael G.
Chemistry: molecular biology and microbiology
Apparatus
Mutation or genetic engineering apparatus
435310, 435315, 435316, 435813, C12M 304
Patent
active
052702073
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is concerned with culture equipment to make a mass culture of bio-organisms including animal cells, human cells, higher plant cells and cells of micro-organisms such as algae, and to maintain the cultured cells in a high density for a long period of time. In additional, this invention is concerned with devices for cell culture and cell maintenance which can be applied to culture equipment for the production of secreted substances and of cellular substances, and to bioreactors for metabolism and extracorporeal artificial organs.
BACKGROUND OF THE INVENTION
High industrial value is widely recognized in the production of substances from animal cells including human cells. They include such substances with wide use for medicine and reagenets as viral antigenic proteins from virus-infected cell, interferons, cytokines, growth factors, monoclonal antibodies, and tissue plasminogen activator.
In addition, mass cells themselves, such as cultured skin keratinocytes, endothelial cells, liver cells and pancreatic Langerhans cells are of great value, since they have successfully been applied in therapy in such ways or forms as skin grafting, hybrid-type artificial blood vessels, artificial organs and transplantation in experimental level. A particular example of success in experimental level is the application of a mass culture of liver cells in the replacement of liver function: A mass culture of liver cells in a vessel, which is connected to a living body from outside through artificial blood vessel, works as an extracorporeal liver, and is expected to overcome liver disfunction in an acute stage.
Technological needs therefore exist in the methods and devices to obtain a mass culture of such bio-organisms as animal cells including human cells, as well as to maintain cultured cells for a long time in a high cell density.
Below, related art is described exemplifying the methods of animal cell culture with the purpose of substance production.
(1) Stationary monolayer culture method.
In this method, cells are cultivated in the state that cells adhere, either actively or passively, to the surface of flat substratum, such as glass and plastics. Plastic culture bottles have widely been used. The use of culture vessels, each with a large surface of multi-layered plastic plates settled in a cuboid module, is the representative technique of mass cell culture (Weiss, R. S. & Schleicher, J. B., Biotech. Bioeng. 10:601-616 (1968). The technique using this type of culture vessel is generally operated with batch culture method, i.e., a method in which cells inoculated in a vessel are fed with culture medium for a period of time, and then the culture is terminated yielding cells and spent medium. Although being the most basic method of mass cell culture for adherent cells, this method has such restriction that the number of cells cultivated is relatively small per volume of culture vessel, that man power for handling culture vessels and feeding cells is large, and that a culture vessel is costive, if it is disposable.
(2) Movable monolayer culture method
In this method, a culture vessel is moved, or rotated while cells grow in a monolayer. This method partially solved problems associated with the stationary monolayer culture method. Using various mechanical means, feeding cells with gas and nutrient has become efficient. The area of substrate surface can be increased extensively. This method is exemplified by a technique (Roller bottle culture method) in which the cell monolayer is formed in the internal surface of a rolling cylindric culture bottle (roller bottle). A number of modifications of the roller bottle culture method have been attempted in order to increase cell density per device volume. In one example, a sheet of wavy plastic thin plate and a sheet of flat plastic thin plate are alternatively rolled in within the interior of the roller bottle (Sterilin, Bulk Culture Vessel, Sterilin Ltd., Teddington, Middlesex).
The movable monolayer culture method is for increasing the contact
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patent: 3617541 (1971-11-01), Pan
patent: 3966599 (1976-06-01), Burkhead
patent: 3980561 (1976-09-01), Miyagi et al.
patent: 4454038 (1984-06-01), Shimodaira et al.
patent: 4940540 (1990-07-01), McDowell
Fuzimori Takao
Matsumura Toshiharu
Sawai Yasuko
Suzuki Jun
Beisner William H.
Meiji Milk Products Company Limited
Wityshyn Michael G.
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