Abstract
The present invention relates to a deepwell plate system, comprising a deepwell plate and a lid system which can be detachably fitted to the deepwell plate by snap- or clamp-fastening means so as to tightly seal the deepwell plate and to a method for the cultivation of cells within the deepwell plate system according to the present invention.
Claims
1. A deepwell plate system comprising a) a deepwell plate comprising a frame and 24 or 96 deepwells, wherein at least one well comprises at least one inner structure; and b) a lid system, comprising an inner cover, at least one filter membrane and an outer cover, wherein the outer cover covers simultaneously all of the openings of the deepwells and includes at least one integrated lock element as a first locking portion, wherein said first locking portion can be detachably fitted to at least one second locking portion located on the frame of the deepwell plate, and wherein the first locking portion of the outer cover is a snap-fastening means, wherein the snap-fastening means comprises as least a circumferential indentation as the first locking portion extending outwardly of a plate matching lower portion of the rim of the outer cover to be engaged with at least a complementary circumferential protrusion as to the second locking portion extending outwardly of a lid matching upper portion of the deepwell plate.
2. The plate system according to claim 1, wherein a cross section of at least one well is one of a circular shaped, flower-shaped or star-shaped.
3. The plate system according to claim 1, wherein the inner structure is a symmetric or asymmetric inner structure.
4. The plate system according to claim 1, wherein the inner structure is a projection or an elevation of the wall of the well.
5. The plate system according to claim 1, wherein the at least one inner structure of the wall of the well is a vertical mixing baffle.
6. The plate system according to claim 1, wherein the inner structure is a projection or an elevation of the bottom of the well.
7. The plate system according to claim 6, wherein the projection or elevation of the bottom of the well is a symmetric or asymmetric slope.
8. The plate system according to claim 1, wherein a horizontal cross section of at least one well is asymmetric.
9. The plate system according to claim 1, wherein the lid system is integrally composed of the outer cover and the at least one filter membrane.
10. The plate system according to claim 1, wherein the lid system is integrally composed of the outer cover, the at least one filter membrane and the inner cover.
11. A method for the cultivation of cells, wherein the cells are cultivated in a deepwell plate system according to claim 1.
Description
(1) The invention is further explained with reference to the accompanying drawing figures, provided for purposes of illustration only and not intended to define the scope of the present invention.
(2) FIG. 1 is a cross-sectional view of the deepwell plate system according to the present invention.
(3) FIG. 2a shows a fragmentary cross-sectional view of the lid system of the deepwell plate system.
(4) FIG. 2b shows a fragmentary cross-sectional view of an alternative embodiment of the lid system.
(5) FIG. 3a is a fragmentary cross-sectional view of one embodiment of the lock element as a snap-fastening means.
(6) FIG. 3b shows a fragmentary cross-sectional view of another embodiment of the lock element as a snap-fastening means.
(7) FIG. 3c is a fragmentary cross-sectional view of yet another embodiment of the lock element as a snap-fastening means.
(8) FIG. 4a shows a fragmentary cross-sectional view of one embodiment of the lock element as a clamp-fastening means.
(9) FIG. 4b shows a plan view of the deepwell plate system with the clamp-fastening means described in detail with reference to FIG. 4a.
(10) FIG. 5a shows a fragmentary cross-sectional view of another embodiment of the lock element as a clamp-fastening means.
(11) FIG. 5b is a plan view of the deepwell plate system with the clamp-fastening means described in detail with reference to FIG. 5a.
(12) FIG. 6 shows perspective views of individual wells.
(13) FIG. 7a shows a perspective view of one individual well with a vertical mixing baffle.
(14) FIG. 7b shows a perspective view of one individual well with an inner structure in form of a slope.
(15) FIG. 7c shows a perspective view of one individual well with an inner structure in form of an asymmetric slope.
(16) FIG. 8a shows the cross section of a well with four edged mixing baffles.
(17) FIG. 8b shows the cross section of a well with six edged mixing baffles.
(18) FIG. 8c shows the cross section of a well with four round mixing baffles.
(19) FIG. 8d shows the cross section of a well with six round mixing baffles.
(20) FIG. 8e shows the cross section of a well with four big round mixing baffles.
(21) FIG. 8f shows the cross section of a well with a four-edged flower-shape.
(22) FIG. 8g shows the cross section of a well with a five-edged flower-shape.
(23) FIG. 8h shows the cross section of a well with a six-edged flower-shape.
(24) FIG. 8i shows the cross section of a well with a different six-edged flower-shape.
(25) FIG. 8j shows the cross section of a well with a five-edged star-shape.
(26) FIG. 8k shows the cross section of a well with a different five-edged star-shape.
(27) FIG. 8l shows the cross section of a well with a six-edged star-shape.
(28) FIG. 8m shows the cross section of a well with a different six-edged star-shape.
(29) Referring to FIG. 1 of the drawings, one embodiment of the deepwell plate system 100 according to the present invention is shown, consisting of deepwell plate 50 which comprises a plurality of wells 20 which are enclosed by frame 10 of deepwell plate 50. Each well 20 is open to the top for receiving, for example, liquid samples. Deepwell plate 50 comprising the plurality of wells 20 and frame 10 is essentially in form of a rectangle. Lid system 60 can be detachably fitted to deepwell plate 50 in order to seal the top openings of all wells 20 simultaneously in a liquid-tight fashion. Lid system 60 consists of at least outer cover 30 and inside filter membrane 32, generally having the same geometry as the principal surface of the deepwell plate 50.
(30) Referring to FIG. 2a, wherein lid system 60 of deepwell plate system 100 is shown in greater detail. Rim 43 of outer cover 30 mates with lid-matching upper portion 13 of frame 10. When lid system 60 is attached to deepwell plate 50, filter membrane 32 comes to lie on the upper surface of frame 10 and is preferably snugly compressed by the attachment of lid system 60 to deepwell plate 50.
(31) In another embodiment, and referring now to FIG. 2b of the drawings, lid system 60 comprises outer cover 30, filter membrane 32 and inner cover 34. Rim 43 of outer cover 30 is formed to overlap lid-matching upper portion 13 of frame 10. Filter membrane 32 and inner cover 34 preferably have the same geometry as the principle surface of the deepwell plate 50 facilitating their compression when lid system 60 is attached to deepwell plate 50. Hence, all openings of wells 20 are sealed by filter membrane 32 and inner cover 34 in a leak-tight fashion.
(32) Preferably, outer cover 30 comprises small holes in a number according to the number of wells 20 of deepwell plate 50 which come to lie exactly above the center of the openings of wells 20. Filter membrane 32 preferably does not comprise any holes, but is permeable for gases to provide for the exchange of for example oxygen between the outside air and wells 20. Inner cover 34 comprises small holes in alignment with the center of the openings of wells 20 and is preferably made out of a resilient hydrophobic material. The deepwell plate system 100 thus achieves a hermetic sealing of wells 20 by virtue of compressing filter membrane 32 and inner cover 34 when lid system 60 is attached to deepwell plate 50 while still allowing gas exchange. This makes deepwell plate system 100 especially suitable for cell culture procedures.
(33) Referring now to FIG. 3a, lock element 70 in one embodiment is a snap-fastening means. Rim 43 of outer cover 30 overlaps or matches the upper portion of frame 10. In this particular embodiment, plate-matching lower portion 40 of rim 43 of outer cover 30 comprises protrusion 42 extending inwardly, i.e. facing frame 10, preferably lid-matching upper portion 13. Lid-matching upper portion 13 of frame 10 on the other hand comprises protrusion 12 which extends outwardly, i.e. facing rim 43 of outer cover 30, preferably plate-matching lower portion 40. As at least outer cover 30 is made preferably of a resilient material, outer cover 30 comprising filter membrane 32 can simply be pushed downwards to close the deepwell plate 50 until protrusion 42 snaps or clicks over protrusion 12 thereby securing lid system 60 onto deepwell plate 50. To detach lid system 60 from deepwell plate 50, lid system 60 simply has to be pulled away from deepwell plate 50 using force until protrusion 42 of outer cover 30 disengages from protrusion 12 of frame 10 by snapping over protrusion 12.
(34) Another embodiment of lock element 70 as a snap-fastening means is shown in FIG. 3b. Here, plate-matching lower portion 40 of rim 43 of outer cover 30 features indentation or groove 44. To seal wells 20 of deepwell plate 50, lid system 60 can be pushed downwards until indentation 44 snaps over protrusion 12 of lid-matching upper portion 13 of frame 10.
(35) Yet another embodiment of lock element 70 as a snap-fastening means is shown in FIG. 3c. In this embodiment plate-matching lower portion 40 of rim 43 of outer cover 30 features protrusion 42 extending inwardly, i.e. facing frame 10, preferably lid-matching upper portion 13 of frame 10. Lid-matching upper portion 13 of frame 10 on the other hand features indentation or groove 14. To close deepwell plate 50 with lid system 60, lid system 60 has simply to be pushed downwards until protrusion 42 snaps or clicks into indentation 14 of frame 10, thereby securing lid system 60 on deepwell plate 50.
(36) All of the protrusion/indentation combinations shown in FIGS. 3a, b and c may be formed as pairs of at least two, which would then preferably be located on opposite sides of deepwell plate system 100, or at least one part of the protrusion/indentation combination is formed in a circumferential fashion.
(37) Referring to FIG. 4a, another embodiment of lock element 70 is a clamp-fastening means. Here, rim 43 of outer cover 30 integrally provides clamp 46 which reaches to the side wall 47 of frame 10. Side wall 47 of frame 10 features notch or aperture 16. To secure lid system 60 onto deepwell plate 50, lid system 60 has to be pushed downwards until the hook-shaped end of clamp 46 engages with notch 16. For the purpose of detaching lid system 60 from deepwell plate 50, fastening clamp 46 can be pulled away from deepwell plate 50, so that it disengages from notch 16.
(38) FIG. 4b shows a plan view of the deepwell plate system 100 closed by the clamp-fastening means of the lid system 60 described in detail in FIG. 4a.
(39) Referring now to FIG. 5a, another embodiment of lock element 70 as a clamp-fastening means is shown in cross-sectional view. In this embodiment, side wall 47 of frame 10 of deepwell plate 50 integrally provides clamp 18. Clamp 18 is intended to be engaged with catch notch 48 provided by the rim 43 of outer cover 30. To close lid system 60, it is thus only necessary to push lid system 60 downwards until the hook-shaped end of clamp 18 clicks into catch notch 48. To detach lid system 60 from deepwell plate 50 fastening clamp 18 has to be pulled away from deepwell plate 50 so that the hook-shaped end of clamp 18 disengages from catch notch 48 and to relieve lid system 60 from deepwell plate 50.
(40) FIG. 5b shows a plan view of deepwell plate system 100 closed by the clamp-fastening means of lid system 60 described in detail in FIG. 5a.
(41) FIG. 6 shows perspective views of individual wells or deepwells 20 of deepwell plate 50 which can have round or square cross sections. It is to be appreciated that the bottom of the wells 20 can either be flat, U-shaped, V-shaped, in form of a frustum or any other suitable shape.
(42) Referring now to FIG. 7a of the drawings, in one embodiment individual wells 20 of deepwell plate 50 comprise at least one inner structure, which can be vertical mixing baffle 26. Vertical mixing baffle 26 is formed by side wall 22 of deepwell 20. Mixing baffle 26 may be in the form of a straight fin, as shown, or may have a triangular or other shape. The base of mixing baffle 26 may extend across approximately one half of bottom 24 of well 20. Vertical mixing baffle 26 promotes in an advantageous manner mixing of the contents of well 20. It also increases the rate of oxygen transfer to the contents of the well 20.
(43) Referring now to FIG. 7b, another embodiment of the inner structure of well 20 can be slope 28 of bottom 24. Slope 28 may extend across approximately one half, preferably the whole of bottom 24 of well 20 and may reach to approximately one half of the height of side wall 22 of well 20. This arrangement assists in moving suspended cells from the lower part of well 20 as the contents of the well are agitated.
(44) Referring now to FIG. 7c, yet another embodiment of the inner structure of well 20 can be asymmetric slope 28. Asymmetric slope 28 is a projection or elevation of bottom 24 of well 20. The base of asymmetric slope 28 may extend across approximately one half, preferably the whole of bottom 24 of well 20 and reach to approximately one half of the height of side wall 22 of well 20.
(45) FIGS. 8a to 8e depict different embodiments of vertical mixing baffles, in particular the cross section of a well with four edged mixing baffles (a), a well with six edged mixing baffles (b), a well with four round mixing baffles (c), a well with six round mixing baffles (d) and a well with four big round mixing baffles (e).
(46) FIGS. 8f to 8i show another embodiment of different geometries of the cross sections of the wells, in particular the cross section of a well which is four-edged flower-shaped (f), the cross section of a well which is five-edged flower-shaped (g), the cross section of a well which is six-edged flower-shaped (h) and the cross section of a well which is of a different six-edged flower shape.
(47) FIGS. 8j to 8m depict yet another embodiment of different well geometries, in particular the cross section of a well which is five-edged star-shaped (j), the cross section of a well which is of a different five-edged star shape (k), the cross section of a well which is six-edged star-shaped (l) and the cross section of a well which is of a different six-edged star shape.
