Abstract:
The invention relates to a culture/exposure device for accommodating cultures ( 72 ), comprising a system for subjecting the accommodated culture ( 72 ) to the action of a gaseous medium. The inventive device also comprises a mechanical flow guide ( 40 ) provided with an entry ( 42 ) for introducing the gaseous medium into the flow guide ( 40 ) and with an exit opening ( 44 ) that discharges above the surface of the culture ( 72 ). The flow guide ( 40 ) forcibly guides the gaseous medium. The invention is characterized in that the inner surface of the exit opening ( 44 ) of the flow guide ( 40 ) opens in a trumpet-like manner in the direction of flow. In addition, an intake tube ( 74, 74 ′) having an intake opening ( 76 ) for drawing in the gaseous medium is connected to the flow guide ( 40 ) and is characterized in that the inner surface of its intake opening ( 76 ) opens in a trumpet-like manner counter to the direction of flow. The invention also relates to a kit consisting of two different bases ( 2, 108 ) and two different tops ( 4; 96 ) that can be combined in any manner to form four different culture/exposure devices.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     The invention concerns culture/exposure apparatuses for the receiving of cultures, a kit for the assembly of such culture/exposure apparatuses as well as a procedure for the culture of prokaryotes.  
       DESCRIPTION OF THE PRIOR ART  
       [0002]     As is disclosed in the state of the technology, culture/exposure apparatuses have been made known, wherein a cell culture contained within a culture/exposure apparatus is subjected to a gaseous medium. As an example thereof, the generically applicable publication DE 100 140 57 (assigned to assignee of the present invention) can be cited as well as EP 1 174 496.  
         [0003]     The culture/exposure apparatus (disclosed in DE 100 140 57) for the reception of cell cultures, employs a culture container, which has a side wall structure conically tapering downward to its bottom with a increasing effective diameter. The said apparatus further is provided with means for subjecting the cell cultures to a gaseous environment, wherein the cell cultures can be treated under predetermined harmful or therapeutic conditions. For this purpose, gases, aerosols, and/or media bearing particulate can directly contact the cell cultures. Among the said gaseous media may be numbered, for example, tobacco smoke for its impingement upon lung cells. The exposure-apparatus encompasses for this purpose, a through-passage, cylindrically shaped, flow directional device. This device is so positioned in the said culture/exposure apparatus above the cell culture that a directed flow of the gaseous medium can be induced therethrough, flowing over the surface of the cell culture and through an annular opening between the said flow device and the wall of the culture container. Such a flow pattern, for example, is produced by a vacuum pump, which is placed in the path of the flow, downstream from the said annular opening. The flow duct, at the entering zone, is connected with a suction fitting, through which the ambient air, test gases or the like are subjected to vacuum and thus can be contactingly conducted over the cell cultures.  
         [0004]     The cited EP 1 174 496 represents in the formation of the exposure apparatus, essentially, the stated publication of the present applicant. Moreover, this publication concerns itself in regard to more exactly determining the dosages of the entrained aerosol particles which deposit themselves on the cell culture. In this regard, the streamlining of the gas flow within the cylindrical flow duct is determined by visibly-marked aerosol particles noted in a pulsed laser beam. Subsequently, from the determined hyperbolically curved streamlines, those streamlines are selected, which travel at a defined distance above the cell culture surface and from which the entrained aerosols can still diffuse upon the cell culture surface. These streamlines are traced back to the entry of the flow duct and thereby an effective cross-section within this streamlining in reference to the entire cross-section of the opening of the flow duct is determined. By means of this effective cross-section, all through-flow aerosols can subject the surface of the cell culture to exposure.  
         [0005]     Practical experience has demonstrated, that prior exposure apparatuses operate unsatisfactorily, because no continuous exchange of the gaseous medium above the cell culture surface exists and no uniformly contacting exposure of the cell cultures can be guaranteed. Obviously, above the cell culture surface, resident “dead zones” have formed. Further in the “exhausted gaseous medium” these dead zones have accumulated, wherein no fresh, gaseous medium can be directed to the cell cultures.  
         [0006]     Also, problems have arisen in respect to the suction fittings, since, for example, the intake of ambient air by means of cylindrically shaped suction fittings is subjected to severe swings away from the predetermined suction intake capacity. On this account, no volume-specific suction is permitted and conversely, undesired suction variations from the vacuum lines occur.  
         [0007]     Thus the invention has the purpose of optimizing the flow characteristics of the gas flow directed over the surface of the culture. Likewise, the invention also has the purpose of improving the suction based removal of a gaseous medium, for instance, from an outer chamber. Finally, another purpose of the invention is to make available extended research possibilities by the cultivation and exposure of prokaryotes.  
       BRIEF SUMMARY OF THE INVENTION  
       [0008]     The invention is a culture/exposure apparatus that optimizes the flow characteristics of the gas flow directed over the surface of the culture and improves the suction based removal of a gaseous medium.  
         [0009]     A culture/exposure apparatus for the receiving of cultures with an arrangement for the treatment of the received culture with a gaseous medium in accordance with a first aspect of the present invention includes a mechanical flow duct with an entry for introducing a gaseous medium into the flow duct and an outflow opening placed above the surface of the culture whereby the flow duct directs the gaseous medium. The inner surface of the flow duct opens itself in a trumpet-like configuration.  
         [0010]     Accordingly, a culture/exposure apparatus for the acceptance of cultures is created, which has a device for subjecting the resident culture with a gaseous medium. This said device possesses a mechanical generation of flow to compel the said gaseous medium to pass through an entry for the introduction of the said gaseous medium into the flow system. The device has further, an outlet opening placed above the surface of the culture. This outlet includes an inner, trumpet-like shaping which widens in the direction of the flow. The advantage of this opening which expands itself in a trumpetlike manner can be found in that, the flow release turbulence, which is especially difficult to control, is avoided at the edges of this type of opening. Normally, at the circumferential rim of a cylindrical discharge duct, turbulent eddies lead to the said dead zones above the culture. With the described special trumpetlike shaped exit opening, assurance is provided, that the flow of the gaseous medium is guided smoothly and free from turbulence over the surface of the culture. Further, the flow, including any therein entrained particles, is distributed to the greatest possible extent, uniformly over the culture surface.  
         [0011]     It should be noted, that the concept “trumpet shaped” is not limited to circular configurations, but may encompass, for example, lengthened openings, (rectangular), square, polygonal, rotation-symmetrical or other opening cross-sections. The decisive factor is, principally, that the opening cross section maintains an increasing cross-section to the exit area. Conversely a linear outlet in the form of a conical frustum does not bring about the desired result, nor does any “tulip shaped” outlet.  
         [0012]     Note should be taken that, the general concept of “culture” or “cell culture” encompasses, not only cell culture, but also the well known eukarotic cultures, the prokaryotic cultures and bacterial cultures and the like.  
         [0013]     A culture/exposure apparatus for the reception of cultures with an apparatus for the exposing of the accepted culture with a gaseous medium in accordance with a second aspect of the present invention includes a suction fitting having a suction opening for the intake of the gaseous medium and an outlet that is connected with a flow guide for conducting the gaseous medium to a plane above the culture. The inner surface of the suction opening opens itself in a trumpetlike flare counter to the flow direction.  
         [0014]     Accordingly, the culture/exposure apparatus intended for the acceptance of cultures is preferably made with an arrangement for the exposure of the resident culture to a gaseous medium. The said arrangement has a suction fitting with a suction opening for the intake of the gaseous medium and an exit opening, which is connected to a flow diversion for the guidance of the gaseous medium to flow immediately above the surface of the culture. For this purpose, the suction opening of the suction fitting exhibits a trumpet shaped inner surface widening in the direction of flow of the gaseous medium. In this case, analogous to the description made above, namely, that accompanying the trumpet shaped, continually widening suction opening, there is the advantage that dead zones which form themselves above the suction fitting are avoided, and from which, no fresh ambient air can be removed.  
         [0015]     A construction kit for the assembly of a culture/exposure apparatus in accordance with a third aspect of the present invention includes separable upper and lower parts, the parts being separable to access a culture container. The lower part is configured to contain the culture container, and may include a supply unit for furnishing the cell culture in the culture container and a heater for temperature regulation of the liquid medium. The upper part supports an apparatus for the exposure of culture in the culture container to a gaseous medium. The exposure apparatus includes a suction fitting for the intake of the gaseous medium and a flow guide for the conductance of the gaseous medium to a plane above the surface of the culture.  
         [0016]     Accordingly, a construction kit for the assembly of a culture/exposure apparatus is made, which contains four kit elements, namely, first, top parts separable from a culture container for access to the culture container, second, top parts with an apparatus for the exposure of the culture in a culture container to a gaseous medium, wherein the said exposure apparatus has as a third item, a suction fitting for the suction-removal of the gaseous medium and a flow directional means connected with the suction fitting for the guidance of the gaseous medium to the zone above the surface of the culture. The kit possesses further as a fourth item, a lower part element that accepts at least one culture container and may include a supply unit for furnishing the cell culture in the culture container and a heater for temperature regulation of the liquid medium. Thus, principally four different culture/exposure apparatuses can be assembled. These would be: 
        a first with an lower part element for the cultivation of cell cultures (or more generally of eukarotic cultures), which especially permits a submerse and basal nutrition with a feed liquid, together with a top piece with the invented flow guidance,     a second with the last mentioned lower part together with a “simplified” flow guidance (for example, with a through-penetrating, cylindrical flow duct)     a third with an lower part for the cultivation of prokaryotes, especially of bacterial in a Petri dish (without external supply with nutrient liquid), together with a top part with the invented flow regulation, as well as     a fourth with the last named lower part together with a top part with a “more simple” flow direction system.        
 
         [0021]     A process for the culture and exposure of prokaryotes with the use of a culture/exposure apparatus with a recess for the reception of a culture container carrying the prokaryotes to be cultured as well as an apparatus for the exposure of the prokaryotes residing in the culture container to a gaseous medium in accordance with a fourth aspect of the present invention includes the exposure apparatus having a suction fitting for the intake of a gaseous medium and a flow duct connected with the suction fitting for the conducting of the gaseous medium to a plane above the resident prokaryotes in the culture container.  
         [0022]     Accordingly, a procedure is given for the cultivation of prokaryotes with the aid of a culture/exposure apparatus with a receptor for the acceptance of a culture container holding the prokaryotes to be cultivated and also an apparatus is made for the exposure of the prokaryotes received in the said culture container to a gaseous medium. In this arrangement, the exposure apparatus comprises a suction fitting for the intake of the gaseous medium, a flow diversion means connected with the said suction fitting for the guidance of the gaseous medium over the surface of the prokaryotes residing in the culture container. In this operation, it is, in the first place, advantageous to create a culture/exposure apparatus, wherewith also prokaryotes (for instance, bacteria, fungi and the like) can be exposed to a predetermined gaseous medium, whereby their reaction thereto can be investigated. Up to now, such investigations were carried out only on eukaryotes, that is, mammalian cells. Prokaryotes, or special bacteria were cultivated and investigated only in connection with a liquid active material, for example cultivated when encapsulated in agar.  
         [0023]     A culture/exposure apparatus for the carrying out of the above procedure in a fifth aspect of the present invention includes a recess for the reception of a culture container carrying the prokaryotes to be cultured as well as an apparatus for the exposure of the prokaryotes resident in the culture container to a gaseous medium. The exposure apparatus includes a suction fitting for the intake of the gaseous medium and a flow duct connected with the suction fitting for the conductance of the gaseous medium over the prokaryotes resident in the culture container.  
         [0024]     Accordingly, a culture/exposure apparatus for the carrying out of a procedure described above with a recess for the receiving of a culture container with the prokaryotes to be cultivated as well as an apparatus for the exposure of the prokaryotes which are in the said container to a gaseous medium. When this is done, the exposure apparatus includes a suction fitting for the suction-removal of the gaseous medium and a flow guidance means connected with the said suction fitting for the guiding of the gaseous medium over the surface of the prokaryotes placed in the culture container.  
         [0025]     The invention, as well as further features and advantages is now to be more closely described and explained with the aid of the attached drawing of embodiments. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0026]      FIG. 1 a  schematic longitudinal cross-section through an invented culture/exposure device having the guidance of flow in accord with the invention,  
         [0027]      FIG. 2 a  schematic, profile view in section through an invented culture/exposure device having the guidance of flow in accord with the invention,  
         [0028]      FIG. 3 a  schematic plan view on the lower part of an invented culture/exposure device,  
         [0029]      FIG. 4  (i.e.,  4   a  to  4   c ) respectively, a sectional view, a perspective view angularly seen from above, a perspective view angularly seen from below of an invented flow duct,  
         [0030]      FIG. 5  (i.e.,  5   a  and  5   b ) respectively, a schematic top view and a profile view of an annular orifice in the invented culture/exposure device for the uniform apportionment of the suction flow about the guided flow,  
         [0031]      FIG. 6  (i.e.,  6   a  and  6   b ) respectively, a profile view and a plan view of a flow-spin body which is placed in the invented flow guidance,  
         [0032]      FIG. 7 a  schematic sectional view through the placement of an invented flow duct and a culture container with a culture placed therein,  
         [0033]      FIG. 8  (i.e.,  8   a  and  8   b ) respectively, a schematic sectional view of an invented suction fitting in accord with a first embodiment and a schematic plan view of a bottom zone of this invented suction fitting,  
         [0034]      FIG. 9  (i.e.,  9   a  and  9   b ) respectively, a schematic sectional view of an invented suction fitting in accord with a second embodiment and a schematic plan view of a bottom zone of this invented suction fitting,  
         [0035]      FIG. 10 a  perspective, angular view of an additional upper component for the invented kit for the assembly of an invented culture/exposure device,  
         [0036]      FIG. 11 a  perspective profile view of an additional lower part for the acceptance of cell culture containers with a supply apparatus for delivering to the cell cultures a fluid medium, which said apparatus is a component of the invented kit for the assembly of an invented culture/exposure device, and  
         [0037]      FIG. 12 a  perspective profile view of an invented culture/exposure device assembled from the upper component of  FIG. 10  and the lower part of  FIG. 11 . 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0038]      FIG. 1  shows a schematic, longitudinal cross-section through an invented culture/exposure apparatus. The said apparatus is made in a nearly boxlike form and consists, accordingly, of two halves, one superimposed on the other, namely an assembly of an lower part  2  and an upper part  4 . In the combined condition, lower part  2  and upper part  4  can be held together by a fastener  6  in the form of a latch. The lower part  2  contains, in this example shown in  FIG. 1 , three recesses  8  formed to receive three culture containers  10 . Obviously, this number can be optionally selected. The recesses  8  are cylindrical borings in the blocklike lower part  2 , as may be more clearly seen in the top view of  FIG. 3 . Also, the culture containers  10  have the form of a circular, open container, wherein the outer walls are obviously cylindrical. The height of said walls of the containers  10  is somewhat lower than the depth of the said cylindrical recesses  8 .  
         [0039]     An ejector mechanism  12  is provided for the removal of the culture containers  10 , which is shown with particular clarity in the section view of  FIG. 2 . The ejector  12  includes a cylindrical penetrative boring  14 , which extends itself from the bottom of the lower part  2  up into the recess  8 . As seen from the said bottom of the lower part  2 , this boring  14  is made with an offset  16  which provides an abutment for a return spring  18 . Guided for back and forth movement within this boring  14  is an ejector pin  20  and the outside diameter of said pin is compatible with the smaller inside diameter of the boring  14 , upward from the offset  16 . The ejector pin  20  has a cylindrical head  22 , the outside diameter of which slidingly corresponds to inside diameter of the penetrative boring  14  in its larger section. In this way, an exact guidance of the ejector pin  20  in the penetrative boring  14  is assured. On the underside of the said head  22  is attached the return spring  18 . Thus the return spring  18  prestresses the ejector pin  20  in a direction away from the recess  8 . On the flat, outer side of the head  22  is to be found attached a lever  24 , the active end of which pivots in the longitudinal direction of the boring  14  about an axis of rotation  26 , slightly to the side of the boring  14 . The opposite end of this lever  24  protrudes from the underside of the lower part  2  in the form of a manually activated handle  28  and so accessibly extends out of the culture/exposure apparatus. As may be seen in  FIG. 1 , for all three ejection mechanisms  12 , one, common pivot axle  26  in the form of continuous shaft is provided to extend itself completely through the lower part  2 . This pivot axle  26  is motionlessly fixed in the lower part  2 , while the lever  24  can freely rotate about it. Thus there can be found, extending out of the longitudinal side of the lower part  2  three handles  28 , with which the three culture containers  10  may be individually ejected by hand. The lever  24 , in detail, possesses a rounded activation cam  30 , which raisingly contacts the open end face of the head  22 . This activation cam  30  allows the pivotal movement of the lever  24  to be carried out in the most friction-free manner possible for the reciprocal movement of the ejector pin  20 . The ejector pin  20  meets, in the upper, smaller diameter part of the boring  14  an annular seal  32 , which closes off the recess  8  from the lower section of the ejector mechanism  12 . Obviously, any other kind of ejection mechanism is possible, with which the culture container  10  can be more easily removed from its recess  8 .  
         [0040]     The lower part  2  is, essentially, hollow, and forms around the discussed recess  8  a liquid-tight chamber  34  which is filled with a liquid for the temperature regulation of the recess  8  and thereby also provides temperature regulation of the culture which is in the culture container  10 . For temperature control on the chamber  34  can be found a liquid inlet  36  and a corresponding liquid outlet  38  (clearly seen in  FIG. 3 ). These fittings  36 ,  38  can be connected to an external heating circulation for the adjustment of the temperature in the chamber  34 . It is obviously possible that alternative heating apparatus can encompass the recess  8 , for instance, a heating coil or the like, with which the culture container  10  can be kept at a predetermined temperature.  
         [0041]     The top-part  4  encompasses an exposure apparatus for the subjection of the culture in the culture container  10  to a gaseous medium. The gaseous medium can be, for example, a pure gas. That is to say, all the therein contained substances such as atoms, molecules and the like find themselves in the gaseous phase. The gaseous medium can also be a carrier for entrained solids and/or liquid particulate, or again may be a mixture of the above, for the purpose of bringing a gaseous medium into contact with the culture. Further it is possible that the gaseous medium may be or may carry such substances as aerosols, atomized liquids, small droplets, or plant-protection means such as spray fogs, Brownian size particulate, solid particulate such as wood dusts, or colloidal suspensions in gas, or atomized suspensions or yet emulsions. For example, the loading of lung cells with cigarette particulate can be investigated in this suspended form. The here numbered materials are not conclusive, but may further vary in accord with the investigations at hand.  
         [0042]     The exposure apparatus encompasses a flow duct  40  with an entry  42  in the form of a connection fitting and an exit fitting  44 , which opens closely above the surface of the culture in the culture container  10  located in the lower part  2 . The flow duct  40  includes a cylindrical transition section  46  with a cylindrical inner boring, which blends continuously in the flow direction into the widening trumpet opening inner surface of the exit opening  44 . This inner surface is, in the flow direction, preferably hyperboloid in shape (see, in particular,  FIGS. 4   a - 4   c ). The outer shape of the flow duct  40  is independent of the hyperboloid inner surface. In accord with the application (composition of the aerosols, etc.) it is possible that various shapes of the opening edges  48  of the exit opening  44  can be advantageous (for instance, rounding off, edges being as sharp as possible and the like). The inner surface of the outlet opening  44  runs onto the outlet rim  48  exactly in a horizontal plane. That is to say, the hyperbolic shape of the section inner surface is so designed, that it possesses a curving to the horizontal. All together, the hyperbolic curve generates itself from the completely vertical run of the flow guide section  46  ( FIG. 2 ) and curves into the present fully, horizontal direction at the outlet edge  48 . This transition of flow direction leads to a flow turning a 90° angle radially away from the central axis. This special geometry makes possible a smooth, turbulence-free outward flow, which, among other things, assures the continual feed of fresh, gaseous medium onto the culture surface. Moreover, the circumferential, concentration apportionment of the medium onto the surface to be treated is nearly completely uniform.  
         [0043]     The flow duct  40  is frictionally held in a penetrative boring  52  in the upper part  4 , which boring extends from the top side thereof and opens into an inner chamber  50 . In the outside surface of the cylindrical guide section  46  is a is a ring shaped groove  54  designed to accept a complementary ring sealing means, such as an O-ring. This ring shaped sealing means now between the outside wall of the flow duct  40  and the inner wall of the through boring  52  seals off, in an airtight manner, the outer space of the culture/exposure apparatus from the inner chamber  50 . The flow duct  40  is slidably and longitudinally placed in the through boring  50 , whereby the distance of the opening edge  48  to the surface of the culture in the culture container  10  can be adjusted. For information in this regard, see the more detailed discussion below.  
         [0044]     The inner chamber  50  forms, in the assembled condition of the lower part  2  and the upper part  4  with the recess  4 , a closed inner space, cylindrical in shape, wherein the inner chamber  50  and the recess  8  fit into one another without edge impact damage.  
         [0045]     In the cylindrical guidance section  46  is inset a twist body  56 , which is held by frictional closure. For details of the twist body  56 , refer to  FIGS. 6   a,    6   b.  The twist body  56  is a short cylindrically shaped piece, the outer diameter of which corresponds to the inner diameter of the cylindrical section of the guidance device  40  into which three neighboringly placed, spiral shaped blades  58  are incised. Obviously, the number of the neighboring blades in relation to the length of the entire twist body is of such a nature, that essentially, they follow a path through half a full rotation about the cylinder shaped twist body  56 . Further, the blades  58  are placed so close to one another, that the remaining web which lies therebetween is as thin as possible. In addition, the through-flow cross-section openings between all blades  58  are as large as possible. Centrally, on the upper end of the twist body  56  is formed a conical apex  60 , the external wall of which makes a transition at its base in an “impact-free” manner into the bottom of the blades  58 . The conical apex  60  is directed counter to the direction of the flow. In this connection, the concept “impact-free” is so selected, that indeed, if necessary, a more or less sharp bend is present between the outside surface of the conical apex  60  and the inner surface of the blades  58  at their deepest position. However, in this is no sharp offset, which otherwise might engender turbulent eddies which could be imparted to the flow. In  FIG. 6   b  the circular base surface of the conical apex  60  is shown in dotted lines.  
         [0046]     Around the cylindrical guiding section  46  of the flow duct  40 , additionally, a disk like, annular orifice  62  is placed, which is slidable in the longitudinal direction. The inner diameter of this said annular orifice  62  corresponds to the outer diameter of the cylindrical guidance section  46  and the outer diameter of the said annular orifice  62  corresponds to inner diameter of the inside chamber  50  of the upper part  4 .(See  FIG. 1 .) On the cylindrically shaped outer wall of the annular orifice  62  is, further, a ring groove  64  into which a sealing ring can be inserted, which seals off the cylindrical outer wall of the annular orifice  62  against the inner wall of the inner chamber  50 . As may be inferred from  FIG. 5   a,  the annular orifice  62  encompasses several axial running through-borings  66 , which allow communication between the upper space section of the inner space  50  with the lower space section of the same although the said sections are separated by the intervening annular orifice  62 . On the upper side of the inner space  50  is also a boring  68  up to a connection fitting  70 , onto which, for example, a hose may be attached and connected to a vacuum pump. In this way, the inner space  50  is placed under suction. For example, it is possible for one vacuum pump to serve all three of the culture/exposure apparatuses shown in  FIG. 1  by means of connection with a common, appropriately subdivided hose. The annular orifice  62  serves also the uniform rotation-symmetric apportionment of the suction and the thereby induced flow about the entire outer surface of the flow duct  40  in order to compensate for the lack of rotational-symmetry from the duct  40  because of the placement of the through borings  66  (see also  FIGS. 5   a,    5   b ). Beyond this, it is possible that various annular orifices  62  per flow duct  40  can be provided, which differ among themselves in the dimensioning of their penetrative boring  66 . In each case, in accord with the adjustment to be made in the suction in the flow dust  40 , an appropriate annular orifice  62  is selected and slipped over the flow duct  40 .  
         [0047]      FIG. 7  shows a schematic sectional view through the flow duct  40  and the culture container  10  for the explanation of the adjustment of the separating distance between the opening  48  and the surface of a culture  72  held in the said culture container  40 . The separating distance of the outflow opening  44  to the surface of the culture  72  is so adjusted, that the through-flow cross-section Q 2  of the annular orifice between the opening edge  48  and the surface of the culture  72  is less than the through-flow cross-section Q 1  in the cylindrical guidance section  46  of the flow duct  40 . With this measure, the flow over the surface of the culture  72  accelerates, which once again avoids the formation of turbulent eddies. As a rule, the separating distance of the outlet rim  48  from the surface of the culture  72  lies in the millimeter range, for example, perhaps only  1  mm. Such a minimal separating distance is also required on the basis, that quite likely the surface of the culture  72  can be uneven in some places. As an additional measure, provision has been made that the ratio of the inner diameter of the container  10  and the outer diameter of the outlet opening  44  on the opening rim  48  is to be so dimensioned, that the flow cross-section Q 3  of the ring opening between opening rim  48  and the inner wall of the container  10  is likewise greater than the previously named through-flow cross-section Q 1 . Generally, no restrictions are imposed on the height of the flow duct  40 —exclusive of the design of the hyperboloidic shape of the outflow opening  44 . Obviously, the cylindrical guidance section  46  may indeed be omitted and the entrance can introduce the flow directly into the hyperboloidal curvature  44 . The diameter of the outflow opening  44 , measured across the rim  48 , is, in any case, determined by adhering to the stated ratio Q 3 /Q 1  with consideration given to the diameter of the culture container  10 , which can be the standard container which is most used in practice.  
         [0048]     The separating distance of the outflow edges  48  from the surface of the culture  72  can be adjusted in multiple ways. First, in the recess  8 , before the inset of the culture container  10  containing the culture  72 , an adjustment platelet of known thickness may be laid therebetween. Subsequently, the flow duct  40 , upon the closing of the lower part  2  and the upper part  4 , may be pushed downward, just so far against the frictional holding force, until the outflow rim  48  impacts the adjustment platelet. Subsequently, the culture/exposure apparatus can be opened, the said adjustment platelet be removed, and in its place the culture container  10  with its resident culture  72  may be inserted. Second, as an alternative to the above, in the top area of the upper part  4 , an adjustment apparatus for the manual or automatic displacing of the said separating distance is provided. The manual adjustment apparatus can, for example, be a spiral drive with a worm gear serving as the manual activation agent. In this case, the spiral drive acts between the upper part  4  and the flow duct  40 . In yet another adjustment arrangement, it is possible that graduation markings may be inscribed on the end of the flow dust  4  extending from the upper part  4 , with which markings one or more selected separating distances may be emphasized. Instead of the frictional binding between the flow duct  40  and the upper part  4 , it may also be advisable to employ a screw fitting, so that the said separating distance may be adjusted by rotating the flow duct  40  to achieve a threaded advance or retraction thereof relative to the upper part  4 .  
         [0049]     For the temperature control and conditioning of the gaseous medium, it is advisable to place a heating coil about the flow duct  40 , which would be connected to a corresponding heating source for the adjustment of the temperature. Alternatively thereto, the flow duct  40  can be constructed of a corrosion resistant metal (titanium could be recommended) or at least be encased within said metal, and a current be directed to and through the corrosion resistant metal, which would result in the warming thereof.  
         [0050]     In addition, it is possible that either between the entry  42  of the flow duct  40  and a therewith bound suction fitting or between the suction fitting  70  and the vacuum pump a flow measuring device based on volume per time unit or on a mass sensitive element with an attendant control valve could be placed in the circuit. In this way for example, the through-flow quantity of the gaseous medium through the said flow duct  40  can be specifically controlled.  
         [0051]     In the  FIGS. 8   a,    8   b,    9   a,    9   b  are shown two alternative designs of invented suction intake fittings  74 ;  74 ′. These said fitting can be connected with the inlet  42  of the multiple flow dusts  40 . The suction fittings  74 ;  74 ′ are constructed, in principle, in a similar manner to the flow duct  40 . That is, these embrace a suction opening  76  with a trumpet shaped inner surface directed counter to the direction of flow. This inner surface possesses, again, in the flow direction, a hyperboloid design. Further, there is connected to this inner surface a cylindrical guidance section  78  with a cylindrical inner surface. The suction opening  76  in, as said, hyperboloid shape, can—otherwise than is indicated in the  FIGS. 8   a,    9   a —advantageously open themselves to the extent, that the generally circumferential edge  80  resides in a horizontal plane. Thereby, once again a flow diversion of the flow present at the suction opening  76  occurs to the extent of approximately 90° away from the horizontal and into the vertical path. In regard to the opening of the suction fitting  76 , is overlaid with a large porosity, foamed material  82 . This foamed material overlay assures a uniform flow and damping within the suction intake fitting  75  itself as a protection against erratic movement and turbulence in the source of ambient air. Nevertheless, the passage of smoke or other solid particulate is not hindered nor filtered out. In this way, prevention is especially extended against lateral currents which strike internally on the suction fitting  74 ;  74 ′ and disturb the uniform distribution of the effective flow within the suction opening  75 . Instead of the said overlaid foamed material  82 , it is also possible that a large opening screening be provided in the suction opening  76 . Alternately also, use may be made of another material which damps cross flows in the suction opening  76 .  
         [0052]     The suction fitting  74  shown in  FIGS. 8   a,    8   b  possesses, in turn, connection fittings  84 , which are directed radially outward. These fittings  84  are connected in the bottom zone of the cylindrical duct section  78  and serve for the connection of lines to the individual entry fittings  42  of the flow ducts  40 . As may be seen in  FIG. 8 , the said, connection fittings  84 , which are radially projecting from the duct section  78 , are placed to be rotationally symmetric about the outer wall thereof. In the illustrated example, four connection fittings  84  are provided, offset at 90° from one another. Obviously, it is allowable, that another number of such connection fittings  84  be chosen, for instance eight thereof. In order to avoid the switching of flows among the four oppositely set connection fittings  84  within the cylindrical duct  78 , therewithin are to be found symmetrically disposed guide vanes  86  in the bottom of duct  78 . These reach from the closed bottom of the said duct  78  approximately twice as high as the plane of the openings of  84 , which same are equally high and near the bottom of duct  78 . In this way, the four partitions  86  form four quarter-circular chambers. The ratio of the length to the diameter of the duct section  78  lies approximately at  2 , whereby the length of the straight line, radial projecting connection fittings  84  more or less correspond to the diameter of the duct  78 . The diameter of the said connection fittings  84  is approximately ten times smaller than the length of the guide duct  78  and the height of the said partitions  86  runs in effect, some three time the diameter of the connection fitting  84 .  
         [0053]     In  9   a,    9   b  is to be seen an alternative embodiment of the connection fittings  74 ′, wherein said fitting possesses four connection fittings  88  projecting axially parallel from the bottom of the guide duct  78 . These four connection fitting  88  enter through appropriately shaped transition sections  90 ,  92  into the cylindrical interior of guide duct  78 . As is evident from  FIGS. 9   a,    9   b,  the transition sections  90 ,  92  are not designed to be rotationally symmetric to the connection fittings  88  although this is contrary to the positioning of the connection fittings  88  themselves in reference to the bottom of the guide duct  78  On this account the corresponding separation walls  94  are provided for the apportionment of the flow into equal parts through the guide duct  78  respectively to the four connection fittings  88 . These walls embrace two separation walls  94  which divide a horizontal (as per  FIG. 9   b ) centerline between the two transition sections  92  into three approximately equal lengths. Further, in this way the said separation walls  94  stand vertically to the said center line as does a third separation wall  94  encompassing the said center line. This third separation wall is placed between the two first named separation walls  94  and divides the transition section  90  within the cylindrical guide duct  80  into two separate parts. In regard to this suction fitting  74 ′, the ratio of the height to the diameter of the guide duct  78  is about 5, the ratio of the diameter of the guide duct  78  to the suction fittings  88  is about 4 an the ration of the height of the separation walls  94  to the height of guide duct is about 7. The three separation walls  94  are equal in height.  
         [0054]     Obviously, such a suction fitting  74  can also attach itself directly onto a flow duct  40 . That is to say, do so without the connection by means of its connection fittings  84 , the connection line and the entry  42  of the flow duct  40 . The cylindrical guide duct  78  of the suction fitting  74  can thus communicate directly with the same diameter into the cylindrical flow section  46  of the flow duct  40  or it can even place the trumpet shaped suction opening  76  of the suction fitting  74  directly into the trumpet shaped opening of the outflow opening  44  of the flow duct  40 . The suction fittings  74 ;  74 ′ can either be positioned in the ambient atmospheric air or in a corresponding space, into which space the entrained particulate from the gaseous medium is artificially injected. That is to say, for example, liquid droplets, by means of appropriate spray nozzles, were atomized into the aid space or again solid materials were blown in through an opening in the said space, or yet a smoking robot could produce smoke in the said room, along with other possibilities.  
         [0055]     In the following, further components in the form of upper and lower parts of an assembled kit for a culture/exposure apparatus are described, which in combination with the above described upper part  2  and lower part  4  can be combined into the construction kit. In this way,  FIG. 10  shows a top part  96  with a simplified exposure apparatus for the treatment of cultures with a gaseous medium. This top part  96  then encompasses, as per  FIG. 10  two major components, namely a top part  96  with a simplified Exposure apparatus for the treatment of culture with a gaseous medium and three essentially container-like recesses with a rotation symmetrical inner surface for the guidance of the gaseous medium up to the surface of the culture. The flow guidance means  98  possess at the height of their opening rims a cylindrical inner profile which transforms into a flat bottom structure. Penetrating from the two longitudinal sides of the upper part  96  into the flow guides  98  are connection fittings  100  and  102 , which are serving as feed and removal conduits for the gaseous medium. The gaseous medium moves, for example, in this way by means of feed functioning connection fittings  102  (which, for example, is bound with the invented suction fittings  74 ;  74 ′ at a side wall into the flow guide  98 . The said gaseous medium is removed therefrom by induced suction through the suction connections  100 , which are functioning as exit means for the flow. The said induced suction can be generated, for example, by connection to a vacuum pump.  
         [0056]     In this case, when seen from a flow-technology standpoint, the matter concerns a simply designed flow guidance means  98 , which does not possess a uniform time and space, homogenous apportionment of the gaseous medium over the entire surface of its outflow opening. Further, the upper part  96 , designed as a liquid tight hollow body possesses also a feed connection  104  and a removal connection  106 , both intended for a hot liquid with which the flow guidance means  98 , and therewith the gaseous medium can be temperature controlled over the culture.  
         [0057]      FIG. 11  shows an additional lower part  108 , which is constructed for receiving culture containers with the cell culture contained therewithin. The cell cultures may be in general, eukaryotes. To this end, the aid lower part  108  possesses three recesses  110  to receive three culture containers  112  (for example, Transwell-inserts) in which the cell culture may be placed. At this point, reference is made to German Patent 198 017 63, which has disclosed an apparatus for cell cultivation. The disclosure of this patent is herewith fully accepted in the present application.  
         [0058]     These culture holding containers  112  (Transwell-inserts) possess, for example, a cup-like shape with a circular cross-section, wherein the diameter of the container opening to the container bottom is diminishly conically shaped. The container bottom consists of a porous plastic material, that is, of polyethylene phthalate. The cell culture-insert offers a liquid permeable carrying structure for a membrane, which, in accord with the current requirement of the cells to be cultivated, can be made from various plastic materials, for instance, from the said polyethylene phthalate. In this operation, the membrane carries the cell culture.  
         [0059]     The recesses  112 , in their bottom areas, are bound with a common line system  114 . This line system in turn, branches into two connection fittings  116 , to which a liquid level controller can be attached with which the cell cultures in the culture containers  112  can be supplied with liquid nutrient substances. For example, a pulse-like control of the feed and removal thereof can be included. The controller, which not described here in greater detail, controls the level of the liquid medium within the culture container  112 . Therewith the cell cultures within the culture container  112  can be periodically nourished in a basal and submersible manner, since, correspondingly, the liquid level of the liquid nutrient can be introduced above or beneath the surface of the cell culture. For further details in regard to the pulse control and level regulation of the liquid medium within the culture container  112 , reference should me made to the above cited patent application. The lower part  108  is designed, once again as a fluid tight hollow body, with a liquid feed connection  118  and a liquid outlet connection  120 . Through these connections a temperature controlled liquid can be conducted through the lower part  108  for temperature regulation of the cultures held in the culture container  112 . The receptacles, i.e. the culture container  112  are likewise liquid tight sealed against the said inner space.  
         [0060]      FIG. 12  shows a variant of a culture/exposure apparatus which can be assembled, wherein the lower part  108  of the  FIG. 11  is combined with the upper part  96  of  FIG. 10 . The combined kit is so designed, that even the lower part  2  and the upper part  4  can correspondingly be combined with the lower or under part  108  and the upper part  96 , in accordance with which culture is to be investigated. For example, for cell cultures the under part  108  would be used, for prokaryote-cultures, under part  2  is recommended, whereby these cultures, then, for the purpose of nourishment in an appropriate substance, for instance, agar, can be held in the culture containers. The said arrangement of upper and lower parts is to be recommended if homogeneity of the most possible timely and spatial characteristics is desired in the apportionment of the gaseous medium to which a culture is to be exposed. In a case wherein this is critical to an investigation, then the upper part  4 , along with the invented flow guidance features should be used, if this is less critical to an investigation, and the upper part  98  would be recommended therewith.  
         [0061]     All together, the culture/exposure apparatus can be so designed, that it can be operated following the equipping of an automatic line by robots with corresponding culture containers,  10  or  112  and provided with the contained cultures to be contained therein (these being, for example, eukaryotes or prokaryote cultures). In this case, however, instead of the clasping mechanism  6  as shown in  FIG. 1 , a robot operable closure can be provided. If this is done, then the lower part  2 ,  108  and the upper part  4 ,  96  can be easily opened and closed by a robot. Further, on the culture containers  10 ;  112 , for example, means can be provided such as magnets, indentations, frictional protuberances and the like, with which a robot arm can easily seize the culture container  8 ,  110  and remove same, and of course, perform the converse operation of replacement. Finally, the culture/exposure apparatus as a whole is so designed, that in a cleaning station, all culture containers  10 ;  112 , after they have been removed, can be easily washed. Another advantage is, that as far as possible, edges and other difficultly accessible places, which come into contact with the gaseous medium, have been avoided.  
         [0062]     Especially, in accord with the invention, with the culture/exposure apparatus as shown in  FIG. 1  (wherein the upper part  4  can be changed to the upper part  96 , if a corresponding homogenous apportionment of the flow is not necessary), prokaryotes (that is, for example, bacteria, fungi, etc.) can be cultivated and subjected to a gaseous medium, which opens a fully novel possibility for investigation with this kind of cultures. Up to now, such investigations were carried out only on cell cultures. Thus it is now possible to carry out the Ames-test, which up to now could only be executed with liquid starting materials (which were encapsulated with the bacteria in agar). This can now be done with the active material carried in the gaseous medium (or with the gaseous medium itself, or with the therein contained liquid or solid entrainment).  
         [0063]     The said investigations can now be extended, since the bacteria were, under certain circumstances, only encapsulated with their nutrient material in agar and the active material flowed over the encapsulated bacteria.  
         [0064]     The flow of the gaseous medium intended for cultivation treatment would be, in such investigations, normally adjusted to the following values: about 80 ml/minute, about 50 ml/minute, about 10 ml/minute, so that the flow within the flow-guidance means lies in the lower ranges of the Reynold numbers and can be classified as linear, non-turbulent flow. Further, in the case of investigations of the effects of tobacco smoke on lung cells, smoke/air mix ratios of 1 to 5 up to 1 to 10 have been adjusted, and this smoke/air mix was held at a temperature of some 35° C. (for example by means of the corresponding heating means about the flow guide ducts  40 ,  98 ). Of the smoke which is carried in the air, in accord with laboratory determinations, about 1% was bound by the lung cells.