Bioreactor, in particular for NMR spectroscopy

Abstract

A description is given of a bioreactor ( 1 ), in particular for NMR spectroscopy, comprising a container ( 7 ) capable of containing a cell culture, a first inlet line ( 6 ) for the inward flow of a culture medium to the inside of the container and a second outlet line ( 9, 10 ) for the outward flow of the culture medium from the container ( 7 ). The first line ( 6 ), an inlet line, is connected to a spiral-shaped device ( 12 ) which has a form such that when the medium is made to flow inside the first line ( 6 ) and made to flow out of the second line ( 9; 10 ), hydrostatic thrust and hydrodynamic forces produce with respect to the cells a condition of simulated reduced gravity inside the container ( 7 ).

1 .- 29 . (canceled) 
   
   
       30 . A method for the culture of cells in a bioreactor comprising the following steps:
 preparing a culture medium;   preparing a culture of desired cells;   
     characterised in that it also comprises the steps of
 arranging said culture inside a container; 
 positioning in said container a spiral-shaped device.; 
 bringing about perfusion of said medium inside said spiral-shaped device so as to obtain, locally in the area in which said cell culture is present, an effect of simulated reduced gravity. 
 
   
   
       31 . A method according to  claim 30 , in which provision is also made for the step of arranging a reservoir for the introduction of said medium, said medium being made to flow from said reservoir to said container and vice versa. 
   
   
       32 . A method according to  claim 30 , also comprising the step of oxygenating said medium inside said reservoir. 
   
   
       33 . A method according to  claim 30 , comprising the step of regulating the temperature of said medium so as to keep it constant. 
   
   
       34 . A method according to  claim 30 , in which the step of preparing a culture medium comprises the step of supplementing or conditioning said medium. 
   
   
       35 . A method according to  claim 34 , in which said medium is devoid of serum or proteins, and/or is recycled and/or has tracers and/or thickeners added in order to obtain optimum growth of the cells desired. 
   
   
       36 . A method according to  claim 34 , in which the step of supplementing said medium comprises the addition of mineral salts, and/or amino acids, and/or glucides, and/or lipids, and/or proteins, and/or growth factors. 
   
   
       37 . A method according to  claim 30 , in which the step of preparing a culture medium comprises the step of introducing into said medium suitable tracers, such as isotopes, and/or chromophores, and/or pH indicators and/or ions and/or contrast means. 
   
   
       38 . A method according to  claims 30 , in which said cell culture comprises animal and/or vegetable cells, and/or micro-organisms and/or yeasts. 
   
   
       39 . A method according to  claim 38 , in which said cells are anchored to substrates or encapsulated. 
   
   
       40 . A method according to  claim 39 , in which said anchorage substrates are microcarrier beads, non-porous, or porous, or constituted from polymers and/or mineral matrices. 
   
   
       41 . A method according to  claim 39 , in which said encapsulation substrates are of the microcarrier type, sponges, of a permanent or biodegradable type, or produced from polyurethane and polypeptide biomaterials. 
   
   
       42 . A method according to  claim 30 , comprising the step of altering the density of said medium. 
   
   
       43 . A method according to  claim 42 , in which said the step of altering the density of said medium comprises the addition to said medium of proteins, serum, deuterated water, methylcellulose, Pluronico™ F68, polyvinyl alcohols, polyvinyl pyrolidones, dextrans, polymers. 
   
   
       44 . A method according to  claim 30 , in which the diameter of said spiral-shaped device and the diameter of said substrates of the culture cells are of the same order of magnitude. 
   
   
       45 . A method for the production of metabolites by microbial means comprising the step of culturing in a bioreactor cells capable of producing said metabolites, characterised in that said cell culture is arranged in a bioreactor comprising a container capable of containing a cell culture, a first inlet line for the inward flow of a culture medium to the inside of said container and a second outline line for the outward flow of the culture medium from said container, where said first inlet line is connected to a spiral-shaped capillary tube, said spiral-shaped capillary tube having a form such that when said medium is made to flow inside said first line and made to flow out from said second line, hydrostatic thrust and hydrodynamic forces produce a condition of simulated reduced gravity with respect to said cells, inside said container. 
   
   
       46 . A method according to  claim 45 , in which said metabolite is glutathione. 
   
   
       47 . A method according to  claim 46 , in which said cell culture is a culture of yeasts. 
   
   
       48 . A method according to  claim 47 , in which said cell culture is a culture of  Saccharomyces cerevisiae.    
   
   
       49 . A method according to  claim 46 , in which said glutathione is localised extracellularly.