Multiwell plate with multiple sample chambers

Abstract

Multi-well plate with a plurality of sample chambers (14), in particular arranged in a grid-like manner, wherein an inlet and an outlet chamber (16, 18) are each assigned to the sample chambers (14), wherein each sample chamber (14) is connected to the inlet chamber (16) assigned to it and to the outlet chamber (18) assigned to it in the lower region via connecting channels (20a, 20b), and with a cover part for the multi-well plate (10), wherein the cover part (12) covers the sample chambers (14) of the multi-well plate (10) towards the top, and wherein the cover part (12) has openings (24) assigned to the inlet chambers (16) of the multi-well plate (10), through which openings, when the cover part (12) is arranged on the multi-well plate (10), fluid can be supplied to the inlet chambers (16) from the outside.

Description

[0001] The present invention relates to a multi-well plate with a plurality of sample chambers, in particular arranged in a grid-like manner, wherein an inlet and an outlet chamber are each assigned to the sample chambers.

[0002] Multiwell plates are known as standard sample vessels. They are used to collect and examine a wide variety of sample types, such as biological cell samples. Individual sample chambers or wells are usually arranged in a matrix on such a plate. A fluid component can usually be filled into the sample chambers, which, for example, supplies a biological sample with nutrients.

[0003] Multiwell plates are known, among others, from DE 10 2008 035 644 A1, in which the sample chambers are each part of a multi-chamber system with each sample chamber having an associated inlet and outlet chamber through which the fluid component flows.

[0004] DE 10 2008 031 265 A1 describes a cell chip system with an inlet chamber, a main chamber, in the bottom area of ​​which there is a cell culture chamber with a sensor chip arranged underneath, and an outlet chamber, in which a vertically displaceable displacement body is provided which is fitted in the main chamber and which, in the lower end position, limits the cell culture chamber at the top, wherein the cell culture chamber has at least one discharge chimney, via which the fluid located underneath can be discharged when the displacement body is moved vertically downwards, wherein the at least one discharge chimney is closed in the lower end position of the displacement body.

[0005] US 2010 / 0 197 525 A1 describes a device for receiving a scientific sample comprising at least one sample and a built-in buffer substance, wherein the built-in buffer substance at least partially surrounds the sample container.

[0006] US 2005 / 0 226 786 A1 describes a multiwell assembly. According to one embodiment, it comprises a multiwell block and a guide plate. The multiwell block comprises a plurality of wells, each well having a liquid-impermeable bottom surface. The guide plate comprises a plurality of liquid passages corresponding to the wells of the multiwell block.

[0007] US Pat. No. 6,136,273 A describes a closure device comprising a flexible cover. The cover, in turn, comprises an array of protruding hollow caps formed integrally with the lid.

[0008] DE 10 2009 059 112 A1 describes a device for determining molecular interactions of nucleic acids and / or proteins and / or peptides comprising at least one hybridization / reaction chamber, and probe molecules selected from the group comprising nucleic acids, proteins and peptides, wherein at least two surfaces bounding the hybridization / reaction chamber have a hydrophilic surface, and wherein said probe molecules are immobilized on at least one of the surfaces in said hybridization / reaction chamber.

[0009] EP 1 391 242 A2 describes a fluidic or microfluidic device that integrates fluidic capability into existing standard configuration microtiter plates for performing single or continuous fluidic manipulations in a high-throughput format.

[0010] US 2006 / 0 088 447 A1 describes a device for dispensing samples, a method for producing a sample applicator, a method for dispensing samples and a base activation device.

[0011] US 4 919 894 A describes an indexing device for a sample container with a plurality of sample holders, comprising a cover with a top and two opposite side walls extending downwards from the top of the sample holders and at the same time allowing access to another section of the sample holders.

[0012] Further state-of-the-art information is available from: LOB, V. [et al.]: Cell-based Assays: Microsensor array-based screening of living cells and tissues. In: BIOspektrum, Vol. 11, 2005, Special Issue Chip Technology & RNA in Research and Application, pp. 511-512. - ISSN 0947-0867 and BRISCHWEIN, M. [et al.]: Chip instead of mouse: Microsensor arrays for chemical testing. In: Nachr. Chem., Vol. 54, 2006, No. 2, pp. 115-120. - Online ISSN 1868-0054.

[0013] A problem with such multi-chamber systems is that the sample chambers cannot be easily sealed at the top. Known sealing systems involve inserts designed as plugs that are manually inserted into the sample chambers from above. A measuring chamber is formed between the lower end of each insert and the sample chamber floor below, in which the sample to be examined is placed.

[0014] This manual insertion of the individual plugs into the sample chambers is time-consuming, especially in multi-well plates with many such sample chambers.

[0015] The object of the present invention is to provide an easy-to-use possibility to cover the sample chambers of multi-well plates with a multi-chamber system at the top.

[0016] This object is achieved by a multiwell plate with several sample chambers having the features of claim 1.

[0017] According to the invention, a multi-well plate is therefore provided, with a plurality of sample chambers, in particular arranged in a grid-like manner, wherein an inlet and an outlet chamber are each assigned to the sample chambers, wherein each sample chamber is connected to the inlet chamber assigned to it and the outlet chamber assigned to it in the lower region via connecting channels, and with a cover part for the multi-well plate, wherein the cover part covers the sample chambers of the multi-well plate at the top, and wherein the cover part has openings assigned to the inlet chambers of the multi-well plate, through which openings fluid can be supplied to the inlet chambers from the outside when the cover part is arranged on the multi-well plate.In other words, the lid seals the sample chambers at the top when mounted on the multiwell plate, particularly in a liquid-tight manner, so that fluid and / or a sample contained therein cannot escape upwards. At the same time, the inlet chambers, to which the fluid must be fed from above to prepare for the actual sample measurements, remain accessible for this purpose.

[0018] As a rule, a single lid section is used for the multiwell plate, which simultaneously covers all sample chamber openings. However, it is also within the scope of the invention to construct a lid section in multiple parts or to provide two or more separate lid sections, each of which individually covers several of the sample chambers of the multiwell plate, but only together cover all of the sample chambers.

[0019] In a further embodiment of the invention, it is provided to provide in the cover part not only openings which are assigned to the inlet chambers of the multi-well plate, but also openings which are assigned to the outlet chambers.

[0020] Overall, the invention achieves that even when the lid part is placed on the multiwell plate, the inlet chambers and optionally also the outlet chambers are accessible from above, for example by means of suitable laboratory equipment, such as pipettes.

[0021] When using multi-well plates, the fluid can be filled into the inlet chambers even when the lid is in place.

[0022] If openings are also provided for the drain chambers, the fluid can be removed from the drain chambers after the measurements have been completed - also with the cover part in place.

[0023] Conveniently, the openings of the lid part assigned to the inlet chambers or, alternatively or additionally, the openings of the lid part assigned to the outlet chambers are arranged at least partially—preferably completely, i.e., across their entire opening plane—without lateral offset above the respectively assigned inlet chamber openings or outlet chamber openings when the lid part is arranged on the multiwell plate. This at least partial overlap between the respective lid part opening and the respective assigned chamber opening ensures that the fluid can be filled into or removed from the corresponding chamber directly from above using a suitable laboratory device, such as the aforementioned pipette.

[0024] It is particularly advantageous if the openings in the lid part assigned to the inlet chambers and / or the outlet chambers are smaller than, or of equal size to, the corresponding inlet or outlet chamber openings. In particular, if the lid part openings are arranged above the respective chambers not only in sections, but completely without lateral offset, as described, this ensures that, regardless of the area of ​​the lid part openings in which the filling pipette, for example, is placed, the fluid flowing from the pipette can always flow directly into the corresponding chamber of the multiwell plate.

[0025] In a particularly preferred embodiment of the invention, the lid part has inserts assigned to the sample chambers, in particular plugs, which are designed and arranged in such a way that, when the lid part is arranged on the multi-well plate, they fit exactly into the sample chambers and close the sample chambers - preferably in a liquid-tight manner - at the top.

[0026] Alternatively, such inserts could theoretically be dispensed with. In such a case, the sample chambers could, for example, simply be covered by a corresponding lid section extending directly above the sample chamber opening plane. This lid section preferably rests directly on the upper edge of the sample chamber when the lid section is mounted on the multiwell plate. The upper edge of the sample chamber is preferably part, in particular the free end, of a sample chamber wall surrounding the sample chamber.

[0027] The lid section covering at least the sample chamber openings is preferably formed by a particularly rigid, plate-like lid wall, with the openings assigned to the respective chambers of the multiwell plate being formed as through-openings in this wall. The openings can be recesses or cutouts in the lid wall.

[0028] To ensure a secure fit of the lid part on the multi-well plate, in a further embodiment of the invention, the lid part has connecting means with which the lid part can be detachably connected to the multi-well plate, preferably via a positive and / or non-positive connection. The multi-well plate additionally has connecting means that interact with the connecting means of the lid part.

[0029] Further features of the present invention will become apparent from the appended claims, the following description of a preferred embodiment, and the accompanying drawings, in which: Fig. 1 is an oblique view of a highly simplified multiwell plate with a lid part in a state in which the lid part is removed from the multiwell plate, Fig. 2 the combination of multiwell plate and lid part made of Fig. 1 in a state where the lid part is placed on the multiwell plate, Fig. 3 a section through the multiwell plate with lid part according to Fig. 2 along the section line II, in a state in which the lid part is removed from the multiwell plate, Fig. 4 a section corresponding to the representation of the multiwell plate from Fig. 3 by a further embodiment of a combination of multiwell plate and lid part in a state in which the lid part is removed from the multiwell plate, Fig. 5 the combination of multiwell plate and lid part according to Fig. 4 in a state in which the lid part is placed on the multiwell plate, Fig. 6 the combination accordingly Fig. 5 when filling an inlet chamber of the multiwell plate with a fluid originating from a pipette, Fig. 7 the combination accordingly Fig. 5 when removing a fluid from a drain chamber of the multiwell plate with a pipette.

[0030] Fig. 1 - Fig. 7 each show different embodiments of a detail of a combination of a multi-well plate 10 and a cover part 12 for such a multi-well plate 10. Both components are manufactured as injection-molded parts from plastic.

[0031] Only a section of the multi-well plate 10 is shown in each case, namely only one sample chamber 14 arranged on a base plate 30 with an inlet chamber 16 assigned to this sample chamber 14 and an outlet chamber 18 assigned to the sample chamber 14. In fact, however, the multi-well plate 10 comprises a plurality of further sample chambers 14, distributed in a grid or matrix manner on the plate 30, extending upwards, in the form of a cup or vessel, and open at the top, each with an assigned inlet and outlet chamber 16, 18. The or each further sample chamber 14 is accordingly also assigned a separate inlet chamber 16 and a separate outlet chamber 18.

[0032] The multiwell plate 10 of the present embodiments is a so-called three-chamber system. Each sample chamber 14 is connected to its associated inlet chamber 16 and its associated outlet chamber 18 in the lower region via one or more connecting channels. Fig. 3- Fig. 7, corresponding connecting channels 20a, 20b are clearly visible.

[0033] The sample to be examined, usually a biological sample (not shown), is placed in the respective sample chamber 14 of the multiwell plate 10. To examine the sample, a suitable fluid is introduced into the respective inlet chamber 16. This fluid flows through the inlet chamber 16 along the connecting channel 20a, first into the sample chamber 14, and from there via the connecting channel 20b into the outlet chamber 18, until the proximity of the respective fluid columns in the chambers is equalized (principle of communicating tubes). Accordingly, a flow of the fluid through the sample chamber 14 is induced. The fluid thus flows along the sample. For example, when examining body cells, this can be used to simulate flow conditions prevailing in the body.

[0034] The samples can be observed visually, for example, by making the bottom of the sample chambers 14 transparent. However, the samples are generally monitored automatically using a sensor chip, in particular a biosensor chip, assigned to each sample chamber 14 of the multiwell plate 10.

[0035] The cover part 12 according to the invention has a plate-like cover part wall 22 made of rigid, inflexible material, in this case plastic, which, when the cover part 12 is placed on the multi-well plate 10, runs parallel to the top side 28 or parallel to the bottom 30 of the multi-well plate 10.

[0036] The cover part 12 has recesses or through-openings 24, 26 which are arranged in such a way that when the cover part 12 is placed on the multiwell plate 10 ( Fig. 2, Fig. 5, Fig. 6, Fig. 7) each opening 24 is arranged directly above the corresponding inlet chamber 16 and each opening 26 is arranged directly above the corresponding outlet chamber 18, ie without the openings 24, 26 each having a lateral offset to the inlet or outlet chamber 16, 18 arranged below them.

[0037] In the Fig. 1- Fig. 7, as with the multiwell plate 10, only sections of the lid part 12 are shown, namely the lid part section corresponding to the corresponding section of the multiwell plate 10. In fact, the lid part 12 therefore has not only the openings 24, 26 shown, but also a plurality of additional openings 24, 26 for each inlet chamber 16 or each outlet chamber 18 of the multiwell plate 10.

[0038] In the present embodiments of the Fig. 1- Fig. 7, the contour of the opening 24 matches the contours of the open top or the opening 32 of the inlet chamber 16 in shape and size, and the contour of the opening 26 matches the contour of the open top or the opening 34 of the outlet chamber 18. However, this is not absolutely necessary. It is important that the openings 24, 26 are arranged at least partially, preferably completely, above the inlet chamber 16 or the outlet chamber 18, i.e., at least in some areas without the lateral offset from them described above.

[0039] If this condition is met, for example, before the actual measurements, with the cover part 12 already in place, the fluid to be filled into the inlet chamber 16 can be filled through the respective opening 24 in the cover part 12 into the inlet chamber 16 arranged below it. This can be done, for example, with a pipette 36 (see. Fig. 6).

[0040] In a similar way, for example, after completion of the measurements on the sample arranged in the sample chamber 14, the fluid then partially located in the outlet chamber 18 as well as the fluid residue still located in the respective inlet chamber 16 can be removed from the chambers 16, 18, for example also with the pipette 36 (cf. Fig. 7).

[0041] The lid part 12 further comprises connecting means 40, which interact with connecting means 42 of the multi-well plate 10 and ensure that the lid part 12 can be firmly, yet detachably, arranged on the multi-well plate 10. The connecting means 40 of the lid part 12 comprise, in the present case, an edge projecting downward relative to the plate-like lid part wall 22, the vertical inner side of which, when the lid part 12 is placed on the multi-well plate 10, bears frictionally against the connecting means 42 by means of a press fit, namely against a lateral outer surface of a vertically extending edge of the multi-well plate 10.

[0042] In the embodiments of the Fig. 4- Fig. 7, the cover part 12, in contrast to the embodiments of Fig. 1- Fig.3 for each sample chamber 14 in each case has a downwardly projecting extension 44, namely a displacement body or an insert, which is introduced into the sample chamber 14 from above when the cover part 12 and the multi-well plate 10 are brought together, and in this case preferably lies in sealing contact with the sample chamber wall 46 which then surrounds it.

[0043] Between the free lower end of the displacement body 44 and the bottom of the sample chamber 14, a measuring space 48 is defined as part of the sample chamber 14, in which the sample sits. List of reference symbols 10 multiwell plates 12 Lid part 14 Sample chamber 16 Inlet chamber 18 Drain chamber 20a connecting channel 20b connecting channel 22 Cover part wall 24 Passage opening 26 Passage opening 28 Top 30 floor 32 Opening 34 Opening 36 pipettes 38 lockable opening 40 lanyards 42 lanyards 44 displacement bodies 46 Sample chamber wall 48 Measuring room

Claims

[1] Multi-well plate with a plurality of sample chambers (14), in particular arranged in a grid-like manner, wherein an inlet and an outlet chamber (16, 18) are each assigned to the sample chambers (14), wherein each sample chamber (14) is connected to the inlet chamber (16) assigned to it and to the outlet chamber (18) assigned to it in the lower region via connecting channels (20a, 20b), and with a cover part for the multi-well plate (10), wherein the cover part (12) covers the sample chambers (14) of the multi-well plate (10) towards the top, and wherein the cover part (12) has openings (24) assigned to the inlet chambers (16) of the multi-well plate (10), through which openings fluid can be supplied to the inlet chambers (16) from the outside when the cover part (12) is arranged on the multi-well plate (10). [2] Multiwell plate according to claim 1, characterized bythat the cover part (12) additionally has openings (26) assigned to the drainage chambers (18) of the multi-well plate (10), through which openings fluid can be supplied to the drainage chambers (18) from the outside when the cover part (12) is arranged on the multi-well plate (10). [3] Multiwell plate according to one or more of the preceding claims, characterized by that the openings (24, 26) of the cover part (12) assigned to the inlet chambers (16) and / or assigned to the outlet chambers (18) are arranged, in the state of the cover part arranged on the multi-well plate (10), at least in regions without lateral offset above the respectively assigned opening (32, 24) of the respectively assigned inlet chamber (16) or outlet chamber (18). [4] Multiwell plate according to one or more of the preceding claims, characterized bythat the openings (24, 26) of the cover part (12) assigned to the inlet chambers (16) and / or the outlet chambers (18) are smaller than the respectively assigned inlet chamber or outlet chamber openings (32, 34) or of the same size. [5] Multiwell plate according to one or more of the preceding claims, characterized by that the cover part (12) in the state arranged on the multi-well plate (10) closes off the sample chambers (14) at the top, in particular in a liquid-tight manner, so that a sample located in the sample chamber (14) cannot escape from the sample chamber (14) at the top. [6] Multiwell plate according to one or more of the preceding claims, characterized byin that the cover part (12) has inserts (44), in particular plugs, assigned to the sample chambers (14), wherein each insert is fitted into the respective sample chambers (14) when the cover part (12) is arranged on the multi-well plate (10) and preferably closes the respective sample chamber (14) in a liquid-tight manner at the top. [7] Multiwell plate according to one or more of the preceding claims, characterized by that the cover part (12) has connecting means (40) interacting in particular with connecting means (42) on the multi-well plate (10), with which the cover part (12) can be detachably connected to the multi-well plate (10), in particular via a positive and / or non-positive connection. [8] Multiwell plate according to claim 6 or 7, characterized by that the inserts (44) of the cover part (12) are detachably fastened in the sample chambers (14) by a press fit when fitted into the respective sample chamber (14). [9] Multiwell plate according to one or more of the preceding claims, characterized by that the cover part (12) is an injection-molded plastic part.

Images