Hitachi, Ltd.

Nobuko Nishimura

Shinichi Fukuzono

Norio Shimizu

Yoji Odawara

Harumi Matsuzaki

Ryoichi Haga

Fumio Maruhashi

Kiyoshi Fujimori

Kenji Baba

Masahiko Ishida

Tomoaki Sumitani

Ryusei Nakano

Yuusaku Nishimura

Setuo Saitoh

This invention relates to an efficient process for culturing recombinant cells which comprises a step of removing a cell proliferation inhibiting substance and/or a substance which inhibits induction of the desired product and a step of inducing production of the desired product.

Process for culturing recombinant cells

In order to investigate an object, such as a culture of micro-organisms, the object is repeatedly captured at two different magnifications by a suitable image pick-up device. The images at the two different magnifications are then analysed by a suitable picture image recognition device and the results of the repeated analysis are compared, thereby to derive a measurement of the change in the object with time. Thus, for a culture of micro-organisms, the number of cells can be determined at one magnification and the number of microscopic spherical bodies can be determined at another magnification, to obtain a measure of the activity of the culture. Preferably, one or more conditions of the object are then controlled on the basis of the measurement of change.

Method and apparatus for investigating and controlling an object

An apparatus for culturing animal cells, includes a diagnosis system to make it possible to diagnose by measuring sizes of the cells by means of image processing while a system of culturing the animal cells is cut off from the outside of the apparatus system, a control system to control the culture conditions of a culturing cistern on the basis of a result of the diagnosis, and a culture medium regenerating system to remove waste contents in a culture medium. In the apparatus of this invention, the culture system and diagnosis system are cut off from the outside of the apparatus system. Therefore, no infection of miscellaneous microorganism, etc., occurs, nor does consumption of valuable cells and products occur. Further, since it is possible to easily obtain data of the proportions of division potential-possessing cells and living cells, the environmental factors to the culturing cistern can be easily and instantly controlled based on the data, and therefore, the culturing efficiency can be enhanced.

Apparatus and method of culturing and diagnosis of animal cells using

Cultivation of microorganisms or animal cells or plant cells is carried out to produce high density cultivation, high cell yield and high production of desired metabolite products by monitoring acetate concentration in culture broth and regulating assimilation of acetate in the culture broth by the microorganisms or animal cells or plant cells to control the acetate concentration to a set value or less. Preferably, an acetic acid-producing bacterium that is inhibited by acetic acid and is capable of assimilating acetic acid is cultured to produce biologically active substances such as enzymes. The bacterium may be a recombinant Escherichia coli and an inducer which acts on a promoter in an expression vector is added to produce the desired metabolite product. The inducer is 3-.beta.- indolylacrylic acid when the promoter is trp-promoter or isopropyl-.beta.-D-thiogalactoside when the promoter is lac-promoter or tacpromoter.

Production of substances with an acetic acid-producing and assimilating

A method of controlling culture wherein cells are aerobically cultured to produce metabolite is characterized by adding substrate and/or inducer to the culture broth, judging the endpoint of the growth of the cells and/or the production of the metabolite or terminating the culture under the guidance of a change in the ratio of the first parameter based on the amount of carbon dioxide evolved by the cell culture to the second parameter based on the amount of oxygen consumed by the cell culture. The ratio is a respiratory quotient, for instance.

Method of controlling culture

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Katsuta, Japan

Nobuko Nishimura