Patent Publication Number: US-2021178400-A1

Title: Combinable cavity tray, assembly of combinable cavity trays, method of manufacturing and use of a combinable cavity tray

Description:
The present invention relates to the technical field of liquid handling, in particular to consumables used for liquid handling, and is directed to a combinable cavity tray and an assembly of at least two combinable cavity trays. A further aspect of the invention is directed to a method of manufacturing a combinable cavity tray and the use of a combinable cavity tray or an assembly of combinable cavity trays for liquid handling. 
     Pipetting tips, such as disposable pipetting tips, are in general well known in the field of liquid handling and are normally provided in a tip tray to be inserted in a tip box. Each pipetting tip is individually and in a loose manner stuck in a corresponding opening of the tip tray and held therein, or rather stopped from sliding therethrough, by the at least partially conically shape of the pipetting tip and the size of the opening being smaller than the maximum cross-sectional area of the pipetting tip. The pipetting tips presented in the tip tray of a tip box are either removed individually and manually by inserting the pipetting tube of a manual pipetting device or removed machine-controlled, either individually or collectively, by inserting the pipetting tube(s) of the pipetting head of an automated liquid handling system or pipetting apparatus. A typical pipetting head of an automated liquid handling system comprises for instance 8, 12, 16, 24, 48, 96, 384 or 1536 pipetting tubes designed for attaching in a sealing manner a pipetting tip each thereto. Such automated liquid handling systems or pipetting apparatuses are for instance described in EP1214977. When the pipetting cycle is over, the pipetting tips are disposed and so are the tip trays used for storage, transportation, and presentation. Only the pipetting box may be reused causing a lot of waste. 
     Pipetting tips are normally made of polypropylene and their mass production is based on injection molding. Polypropylene granulate is first molten and the molten material is then injected into the individual cavities of a mold specifically made for the purpose of manufacturing pipetting tips. Once the material is solid again, or in other words sufficiently cool, the batch of pipetting tips is ejected. Each single and individual cavity allows to produce a single and individual pipetting tip. 
     Although common practice is rather successful, it shows several drawbacks. On the one hand, injection molding manufacturing technology needs expensive tools, namely the for each purpose individually tailored molds. On the other hand, the manufactured and individual pipetting tips must be stored in trays which are a in most cases also manufactured based on expensive injection molding manufacturing technology and represent a disposable good. 
     This results in a lot of plastic material usage having an impact on manufacturing, transporting and waste costs. However, the manufacturing costs are not only driven by the excessive amount of basic material required but also by the high initial costs for designing and manufacturing the mold for injection molding. The tools are expensive for several reasons, in particular because the tools must comprise a high number of cavities (e.g. 32, 64 or 96), require a high precision in steel, must resist high pressures and therefore be massive, require cooling channels in the drift pin for lower cycle times and require heating channels to allow for injection molding without sprue. Moreover, each produced tip must be tested by means of a complex automated system before being packed. 
     The more or less same observations apply to microplates, such as 96 well plates or alike. The essentially only difference is that the handling (such as packaging etc.) of microplates is easier compared to the handling of disposable pipetting tips as the wells of a microplate are provided in an association of multiple wells, i.e. as microplate, and not individually. 
     The object of the present invention is to provide less costly consumables. 
     This object is achieved by the combinable cavity tray according to claim  1 , which allows for a less costly production of consumables and in addition reduces the amount of basic material required for production. 
     The combinable cavity tray for liquid handling according to the invention comprises at least one cavity for receiving a fluid and at least one passage for leading through a cavity of a second combinable cavity tray and/or for leading through a pipetting tube of a pipetting apparatus. The at least one cavity is in particular formed integrally. 
     Integrally in this respect means that the cavity is part of the combinable cavity tray and forms a fixed component. The cavities are in particular not designed or manufactured separately and then linked to the rest of the combinable cavity tray. In other words, the combinable cavity tray is in particular a one-piece-design. 
     The constitution of a combinable cavity tray according to the invention allows for forming an assembly of at least two combinable cavity trays that can be used similar to a microplate (also known as microtiter plate, microwell plate or multiwell) or to a plurality of disposable tips. This concept opens new ways of manufacturing, in particular the implantation of production methods other than injection molding. The renunciation of injection molding results in lower manufacturing costs driven by lower toll costs, i.e. no expensive injection molds are required anymore, lower manufacturing machine costs apply, and higher manufacturing capacities can be realized since more cavity trays can be produced at the same time in parallel. Furthermore, less basic material is required for production, thereby causing lower expenses on raw materials and a reduction of waste deposition and transportation costs. Overall, the use of consumable becomes more sustainable. Moreover, due to the lower production costs compared to conventional disposable pipetting tips made by injection molding, the combinable cavity tray and assemblies thereof can be sold to the consumer for less money and thus reduce the operation costs for a laboratory in general. 
     Another of the advantages of the combinable cavity trays according to the invention is that they provide for a high packing density and therefore require only little space on the worktable compared to e.g. conventional disposable tips presented in a tip box. However, it is not necessarily the case that the combinable cavity trays are positioned right from the start on the worktable itself, but they can also be stored behind the worktable or in a shelf. A gripper is then in charge to provide the combinable cavity trays and position them on the worktable. Nonetheless, the consumer benefits from the little storage space that is required by the combinable cavity trays. The at least one cavity is in particular suitable for handling liquids of liquid volumes between e.g. 10 μl to 10 ml. The overall volume of the cavity is e.g. between 10% to 50% larger as the cavity is not complete filed with liquid for liquid handling. The at least one cavity is in particular cylindric and/or conically shaped, comprising e.g. a diameter between 0.2 to 1.5 cm, in particular of 0.2 to 0.6 cm, and a depth of 0.5 to 10.0 cm, in particular of 1.0 to 5.0 cm. The opening of the at least one cavity is preferably round and comprises e.g. a diameter of 0.2 to 1.5 cm, in particular of 0.3 to 1.0 cm, further in particular of 0.6 cm. The passage, on the other hand, is also preferably round and comprises e.g. a diameter of 0.2 to 1.5 cm, in particular of 0.3 to 1.0 cm, further in particular 0.6 cm. In an example, the passage comprises a smaller diameter (e.g. smaller by 0.1, 0.2, 0.3, 0.4 or 0.5 cm) than the opening of a conically shaped cavity such that an upper combinable cavity tray is positioned higher than the combinable cavity tray of below by more than the material thickness of the edge of the passage. The main body of the combinable cavity tray is e.g. essentially rectangular and comprises e.g. a width of 4 to 20 cm and a length of 6 to 30 cm, in particular a width of 9 cm and a length of 13 cm. Typical cavity densities for a number of 2, 4, 6, 8, 12, 24, 48, 96, 384 or 1536 cavities per combinable cavity tray are therefore approximately 0.08, 0.17, 0.25, 0.33, 0.5, 1, 2, 4, 16 or 64 cavities per cm 2  for an area of 4 cm×6 cm. Further examples can easily be calculated by dividing the number of cavities of a combinable cavity tray by its area in cm 2 . 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the embodiments still to be addressed unless in contradiction, is the at least one cavity formed by thermoforming. 
     A typical thermoforming manufacturing process comprises the steps of heating a plastic sheet to a pliable forming temperature, forming the plastic sheet to a specific shape in a mold, cooling the plastic sheet to a desired shape, and trimming the desirably shaped plastic sheet to create a usable product. Although thermoforming requires molds such as injection molding, the molds are manifold cheaper than the ones for injection molding. However, thermoforming comes along with some process limitations. While forming the plastic sheet to a specific shape in a mold, the material of the initially planar plastic sheet is stretched in vertical direction, but the material can only tolerate a certain lengthening before tearing. This results in a general limitation of the depth of a 3D structure being maximum 4 times its width. To nonetheless provide a stable structure suitable for implementation together with a pipetting apparatus comprising a pipetting head of large numbers of pipetting tubes, such as e.g. 96, or for analyzing a large number of samples in a multitude of test tubes, the actual liquid handling is carried out on the basis of an assembly of at least two combinable cavity trays. Due to the smaller number of cavities in each of the combinable cavity trays compared to the assembly, the depth-to-width-ratio-limitation can be compensated, and a structure can be provided that comprises more cavities per area than could be provided based a one-piece-structure. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, the combinable cavity tray is at least in parts of a thermosoftening plastic or a compound foil of thermosoftening plastic. Thermosoftening plastic are also considered as thermoplastic materials and comprise e.g. polyethylene terephthalate (PET), polystyrene (PS) or polypropylene (PP). The compound foils comprise or consist e.g. two of the above identified thermoplastic materials, in particular PET and PP. Other examples for thermoplastic materials are acrylonitrile butadiene styrene (ABS), polyamide (PA), polylactic acid (PLA), poly(methyl methacrylate) (PMMA), polycarbonate (PC), polyethylene (PE), polyether ether ketone (PEEK), polyvinyl chloride (PVC), celluloid. In one example, polyvinyl chloride (PVC) is explicitly excluded from the group of thermoplastic materials. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, is the at least one cavity a pipetting cavity for aspirating and/or dispensing a fluid. 
     Such a combinable cavity tray is in particular suitable for the provision of an assembly of combinable cavity trays used as substitute for a multitude of single disposable tips in combination with a pipetting apparatus and its pipetting head. The pipetting cavity comprises an opening in the upper region for e.g. connecting to a pipetting tube of a pipetting head and an aperture in the bottom region for aspirating and/or dispensing a fluid. The aperture is e.g. round and comprises a diameter of 0.2 mm to 1.0 mm, in particular of 0.4 mm to 0.7 mm, further in particular of 0.5 mm. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, is the at least one cavity a test tube for analytics and/or diagnostics. 
     Such a combinable cavity tray is in particular suitable for the provision of an assembly of combinable cavity trays used as substitute for a microplate comprising several wells, e.g. a 96-well plate. Opposite to a pipetting cavity, the test tube does not comprise an aperture in the bottom region for aspirating and/or dispensing a fluid. However, the test tube comprises also an opening in the upper region, but this opening is meant for adding and removing samples, chemicals and such. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, comprises the combinable cavity tray at least one positioning means for guiding an assembling process of assembling a first cavity tray and a second cavity tray. It is also possible that the combinable cavity tray comprises, in addition or instead, at least one fixation means for fixing a first cavity tray and a second cavity tray when assembled. 
     The fixation means e.g. prevent the assembly from disassembling. Fixation means can be designed as two cooperating means, one being arranged at the first cavity tray and the other being arranged at the second cavity tray. The cooperating means can be configured as snap-on system, tongue-and-groove-joint, . . . . The positioning means assist the assembling process by guiding the combination of a first and second cavity tray. The positioning means may also be realized by cooperating means, e.g. by a protrusion being arranged at the first cavity tray and a recess being arranged at the second cavity tray. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, comprises the combinable cavity tray n cavities. N is a natural number and calculated by dividing 96 by a natural number ≥2. N is in particular 48, 32, 24, 16, 12, 8, 6, 4, 3 or 2. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, equals the number of cavities the numbers of passages. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, is the number of cavities smaller than the number of passages. The number of cavities is in particular smaller by a factor, the factor being a natural number ≥2. The factor is e.g. 3, 4, 5, 6, 7, 8 or 9. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, are the at least one cavity and at least one passage arranged alternating. 
     Such arrangement allows for the maximum compensation of the depth-to-width-ratio-limitation and is in particular recommended for combinable cavity trays comprising at least 2 cavities and one passage or at least two passages and one cavity. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, comprise the combinable cavity tray a symmetry plane leading through at least one cavity and at least one passage The number of cavities and the number of passages where the symmetry plane leads through is identical. 
     Such a symmetry allows for assembling two identically designed combinable cavity trays (note: one of the combinable cavity trays must be rotated) and thus reduces the number of required tools for manufacturing the combinable cavity trays. 
     In one embodiment of the combinable cavity tray according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, is the combinable cavity tray 180° rotationally asymmetric in reference to an axis orthogonal to the largest two-dimensional extent of the combinable cavity tray, rotationally asymmetric in the sense of cavities and passages interchanging positions when rotated. 
     Such an asymmetry allows for assembling two identically designed combinable cavity trays (note: one of the combinable cavity trays must be rotated) and thus reduces the number of required tools for manufacturing the combinable cavity trays. 
     A further aspect of the invention addresses an assembly of combinable cavity trays comprising at least two combinable cavity trays according to the invention. 
     In one embodiment of the assembly of combinable cavity trays according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, is the total number of cavities 384, 96 or 48. 
     An even further aspect of the invention addresses a method of manufacturing a combinable cavity tray for liquid handling. The method comprises an in particular first step of providing a sheet of at least one thermosoftening plastic. Furthermore, the method comprises an in particular second step of shaping the sheet by thermoforming to comprise at least one cavity and an in particular third step of forming at least one passage into the sheet for leading through a cavity of a second combinable tip tray and/or for leading through a pipetting tube of a pipetting apparatus. 
     The step of shaping the sheet by thermoforming to comprise at least one cavity is in particular a single thermoforming process. There are two main types of thermoforming: vacuum forming and pressure forming, and both can be implemented in connection with the above described method. Vacuum forming uses heat and pressure to draw plastic sheets into its final configuration. Once a sheet is heated and placed over a mold, a vacuum is used to manipulate it into its desired shape. Pressure forming has many similarities to vacuum forming but has the added benefit of additional pressure. This pressure allows for greater detail and texture, making it a solid choice when aesthetics is an issue. 
     In one embodiment of the a method of manufacturing a combinable cavity tray for liquid handling according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, comprises the method further the in particular fourth step of forming at least one aperture in the bottom area of the at least one cavity. 
     This step provides for a pipetting cavity for aspirating and/or dispensing a fluid. The aperture can e.g. be formed by laser techniques or die cutting. 
     In one embodiment of the a method of manufacturing a combinable cavity tray for liquid handling according to the invention, which may be combined with any of the preaddressed embodiments and any of the embodiments still to be addressed unless in contradiction, comprises the sheet a thickness of 0.3 to 1.0 mm, in particular of 0.5 to 0.8 mm, and further in particular of 0.7 mm. 
     An again further aspect of the invention addresses the use of a combinable cavity tray or of an assembly of combinable cavity trays for liquid handling, in particular for receiving a fluid and/or aspirating a fluid and/or dispensing a fluid. 
     Another further aspect of the invention addresses a method of connecting a combinable cavity tray or an assembly of combinable cavity trays to a pipetting apparatus with pipetting tubes. The method comprises an in particular first step of inserting at least one pipetting tube with its first end in a cavity of a combinable cavity tray through the opening of the cavity with a first force to achieve a friction fit between the at least one pipetting tube and the combinable cavity tray. The method comprises further an in particular second step of positioning the combinable cavity tray connected to the at least one pipetting tube on a rigid base and further inserting the at least one pipetting tube in the cavity with a second force being stronger than the first force to achieve a fluid-tight connection between the at least one pipetting tube and the cavity of the combinable cavity tray. 
     In an example, the second force is e.g. 300 N for a combinable cavity tray with 96 cavities or an assembly of combinable cavity trays with in total 96 cavities to achieve a fluid-tight connection between the pipetting tubes and the cavities. The first force for achieving a friction fit of a similar example is e.g. 50 N, 100 N or 150 N. The movement of the combinable cavity tray or assembly of combinable cavity trays necessary for the positioning on a rigid base can be driven by the pipetting apparatus. 
     Furthermore, an alternative method of connecting a combinable cavity tray or an assembly of combinable cavity trays to a pipetting apparatus with pipetting tubes is presented. The method comprises an in particular first step of inserting at least one pipetting tube with its first end in a cavity of a first combinable cavity tray through the opening of the cavity with a first force to achieve a friction fit between the at least one pipetting tube and the first combinable cavity tray. Furthermore, the method comprises an in particular second step of inserting at least one further pipetting tube with its first end in a cavity of a second combinable cavity tray through the opening of the cavity with a second force to achieve a friction fit between the at least one further pipetting tube and the second combinable cavity tray and an in particular third step of positioning the first combinable cavity tray connected to the at least one pipetting tube and the second combinable cavity tray connected to the at least one further pipetting tube on a rigid base and further inserting the at least one pipetting tube and the at least one further pipetting tube in the cavities with a third force being stronger than the first force and the second force to achieve a fluid-tight connection of the at least one pipetting tube and the at least one further pipetting tube to the cavities and to in particular achieve assembling the first combinable cavity tray and the second combinable cavity tray to form an assembly of combinable cavity trays. 
     The first and the second force can be equal or different, e.g. the first force can be stronger than the second force or the other way around. The movement of the first and second combinable cavity tray necessary for positioning them on a rigid base can be driven by the pipetting apparatus. 
    
    
     
       The invention shall now be further exemplified with the help of figures. The figures schematically show: 
         FIG. 1 a    an embodiment of a first combinable cavity tray according to the invention; 
         FIG. 1 b    an embodiment of a second combinable cavity tray according to the invention; 
         FIG. 1 c    an embodiment of an assembly of combinable cavity trays according to the invention; 
         FIG. 2 a    another embodiment of a first combinable cavity tray according to the invention; 
         FIG. 2 b    another embodiment of a second combinable cavity tray according to the invention; 
         FIG. 2 c    another embodiment of an assembly of combinable cavity trays according to the invention; 
         FIG. 2 d    a cross-sectional view of the assembly of combinable cavity trays of  FIG. 2   c;    
         FIG. 3  a further embodiment of a combinable cavity tray according to the invention; 
         FIG. 4  a further embodiment of an assembly of combinable cavity trays according to the invention; 
         FIG. 5  a further embodiment of a combinable cavity tray according to the invention; 
         FIG. 6 a    a further embodiment of an assembly of combinable cavity trays according to the invention; 
         FIG. 6 b    a cross-sectional view of the assembly of combinable cavity trays of  FIG. 6   a;    
         FIG. 6 c    a further cross-sectional view of the assembly of combinable cavity trays of  FIG. 6   a;    
         FIG. 6 d    a further cross-sectional view of the assembly of combinable cavity trays of  FIG. 6   a;    
         FIG. 6 e    an enlarged view of a cross-section of the assembly of combinable cavity trays of  FIG. 6   a;    
         FIG. 7  a stack of several assemblies of combinable cavity trays according to the invention; 
         FIG. 8 a    an assembly of combinable cavity trays according to the invention connected to a multichannel pipetting head; 
         FIG. 8 b    a cross-sectional view of the assembly of combinable cavity trays connected to the multichannel pipetting head of  FIG. 8   a;    
         FIG. 9  an embodiment of a method of manufacturing a combinable cavity tray according to the invention; and 
         FIG. 10  another embodiment of a method of manufacturing a combinable cavity tray according to the invention. 
     
    
    
       FIG. 1 a    shows a combinable cavity tray  10  for liquid handling. This combinable cavity tray  10  is called the first combinable cavity tray  11  (indicated by dashed lines) in the following and comprises one cavity  20  for receiving a fluid and furthermore one passage  30  for leading through a cavity of a second combinable cavity tray (e.g. a second combinable cavity tray as shown in  FIG. 1 b   ). The cavity  20  with its opening  22  is formed integrally such that the first combinable cavity tray  11 , or at least its main body, and the cavity  20  are designed in one piece. The passage  30  is preferably at least as big as or even slightly bigger than the opening of the cavity of the second combinable cavity tray shown in  FIG. 1 b   . The first combinable cavity tray  11 , or at least its main body, is preferably made of a thermosoftening plastic (also known as thermoplastic material; e.g. polyethylene terephthalate (PET), polystyrene (PS) or polypropylene (PP)) or a compound foil comprising thermosoftening plastic(s), and the cavity  20  is preferably formed by a thermoforming process. The meaning of axis x becomes clear when studying  FIG. 1 b    and its description. 
       FIG. 1 b    shows a combinable cavity tray  10  for liquid handling, e.g., by means of liquid handling systems. This combinable cavity tray  10  is called the second combinable cavity tray  12  (indicated by solid lines) in the following and is identical to the first combinable cavity tray shown in  FIG. 1 a    but turned by 180° around an axis x being orthogonal to the largest two-dimensional extent of the second combinable cavity tip tray  12  such that, compared to the first combinable cavity tray shown in  FIG. 1 a   , the passage  30  of the second combinable cavity tray  12  is located where the cavity of the first combinable cavity tray is and the cavity  20  with its opening  22  of the second combinable cavity tray  12  is located where the passage of the first combinable cavity tray is. One could say that the first combinable cavity tray and the second combinable cavity tray  12  are rotationally asymmetric such that cavity  20  and passage  30  interchanging positions when rotated around axis x by 180°. 
       FIG. 1 c    shows an assembly  100  of combinable cavity trays comprising the first combinable cavity tray  11  (indicated by dashed lines) of  FIG. 1 a    and the second combinable tray  12  (indicated by solid lines) of  FIG. 1 b   . The first combinable cavity tray  11  is put upon the second combinable tray  12  such that the cavity  20  of the first combinable cavity tray  11  points through the passage  30  of the second combinable tray  12  and the passage  30  of the first combinable cavity tray  11  is in alignment with the opening  22  of the cavity  20  of the second combinable tray  12 . The assembly is now ready to be used in a manner similar to a one-piece cavity tray comprising two cavities but no passage. The shown assembly can for instance be used as a two-well microplate for analytics and/or diagnostics. 
       FIG. 2 a    shows a first combinable cavity tray  11  for liquid handling, in particular by means of liquid handling systems. The first combinable cavity tray  11  (indicated by dashed lines) comprises one passage  30  for leading through a cavity of a second combinable cavity tray (e.g. as shown in  FIG. 2 b   ) and furthermore one pipetting cavity  21  for aspirating and/or dispensing a fluid. The pipetting cavity  21  comprises an opening  22  on the top side and at least one aperture  23  on the bottom side. The pipetting cavity  21  is formed integrally such that the first combinable cavity tray  11 , or at least its main body, and the pipetting cavity  21  are designed in one piece. The passage  30  is preferably at least as big as or even slightly bigger than the opening of the pipetting cavity of the second combinable cavity tray shown in  FIG. 2   b.  The first combinable cavity tray  11 , or at least its main body, is preferably made of a thermosoftening plastic (also known as thermoplastic material; e.g. polyethylene terephthalate (PET), polystyrene (PS) or polypropylene (PP)) or a compound foil comprising thermosoftening plastic(s), and the cavity for forming the pipetting cavity  21  is preferably formed by a thermoforming process. The first combinable cavity tray  11  comprises two female positioning means  41  for guiding an assembling process of fitting together a first combinable cavity tray and a second combinable cavity tray, the female positioning means  41  being arranged in opposite and non-neighbouring corners of the largest two-dimensional extent of the first combinable cavity tray  11 . The meaning of axis x becomes clear when studying  FIG. 2 b    and its description. 
       FIG. 2 b    shows a second combinable cavity tray  12  for liquid handling, in particular by means of liquid handling systems. The second combinable cavity tray  12  (indicated by solid lines) is designed comparable to the first combinable cavity tray shown in  FIG. 2   a,  in particular in reference to the pipetting cavity  21  with its opening  22  and aperture(s)  23  and the passage  30 . The first combinable cavity tray and the second combinable cavity tray  12  are rotationally asymmetric in relation to the position of the pipetting cavity  21  and the passage  30  in the sense that pipetting cavity  21  and passage  30  interchange positions when rotated around axis x by 180°, axis x being orthogonal to the largest two-dimensional extent of the second combinable cavity tray  12 . However, the second combinable cavity tray  12  comprises two male positioning means  42  instead of two female positioning means, the male positioning means  42  being arranged such in opposite and non-neighbouring corners of the largest two-dimensional extent of the second combinable cavity tray  12  that they can be brought into alignment with the female positioning means of the first combinable cavity tray shown in  FIG. 2   b.    
       FIG. 2 c    shows an assembly  100  of combinable cavity trays comprising the first combinable cavity tray  11  (indicated by dashed lines) of  FIG. 2 a    and the second combinable tray  12  (indicated by solid lines) of  FIG. 2   b.  The first combinable cavity tray  11  is in the process of being put upon the second combinable cavity tray  12 . The pipetting cavity  21  of the first combinable cavity tray  11  points already partially through the passage  30  of the second combinable tray  12  and the passage  30  of the first combinable cavity tray  11  is on its way to be brought into alignment with the opening  22  of the pipetting cavity  21  of the second combinable tray  12 . Furthermore, the female positioning means  41  of the first combinable cavity tray  11  and the male positioning means  42  of the second combinable cavity tray  12  are oriented such that they serve as guiding elements for the last section of the assembling process. The male positioning means  42  and female positioning means  41  can be designed such that they form in addition fixation means, e.g. based on a snap-on engagement, for coupling the first cavity tray  11  and the second cavity tray  12 . When joined completely, the assembly is ready to be used in a manner similar to a one-piece cavity tray comprising two cavities but no passage. 
     Please note that although the passage  30  of the first combinable cavity tray  11  is suitable for leading through a pipetting cavity of a second combinable cavity tray  12 , there is no pipetting cavity  21  of a second combinable cavity tray  12  led through as the first combinable cavity tray  11  is the top-most combinable cavity tray and therefore its passage  30  is used to lead though a pipetting tube of a pipetting apparatus (not shown), e.g. a pipetting apparatus with a multichannel pipetting head, and thus the passage  30  is not only suitable for leading through a pipetting cavity  21  of a second combinable cavity tray  12  but also for leading through a pipetting tube of a pipetting apparatus. It is, of course, possible to design a combinable cavity tray whose passage is in particular specifically configured to lead through a pipetting tube of a pipetting apparatus and use this combinable cavity tray in particular as top-most combinable cavity tray in an assembly of cavity trays. 
       FIG. 2 d    shows a cross sectional view of the assembly  100  of combinable cavity trays of  FIG. 2 c    in completely joined or assembled state. The cross section is drawn along a symmetry plane leading through the one pipetting cavity  21  and the one passage  30  of both the first combinable cavity tray  11  and the second combinable cavity tray  12 , respectively. The first combinable cavity tray  11  is positioned upon the second combinable cavity tray  12  such that the pipetting cavity  21  of the first combinable cavity tray  11  pushes through the passage  30  of the second combinable tray  12  and the passage  30  of the first combinable cavity tray  11  is brought into alignment with the opening  22  of the pipetting cavity  21  of the second combinable tray  12 . Both pipetting cavities  21  comprise an aperture  23 . 
       FIG. 3  shows a top view on a combinable cavity tray  10  for liquid handling. The combinable cavity tray  10  comprises six cavities  20  (indicated by black circles) and six passages  30  (indicated by white circles) such that the number of cavities  20  equals the number of passages  30 . The cavities  20  and passages  30  of the combinable cavity tray  10  are arranged alternating in a 4×3 matrix such that cavities  20 , when viewed in column (four columns in total) or in row (three rows in total), are always arranged next to a passage  30  and not next to another cavity  20 . The combinable cavity tray  10  is designed rotationally asymmetric such that cavity  20  and passage  30  interchange positions when the combinable cavity tray  10  is rotated by 180° around axis x. Axis x is orthogonal to the largest two-dimensional extent of the combinable cavity tip tray  10  and in this example also centric. Furthermore, the combinable cavity tray  10  comprises a symmetry plane (indicated by the dashed lines) leading through the two cavities  20  and the two passages  30  of the middle row. The advantage of such a mirror symmetry (visualized by the two arrows on the right-hand side) is that the combinable cavity tray  10  can be used as first combinable cavity tray and, when turned by 180° around axis x, as second combinable cavity tray in an arrangement of e.g. two combinable cavity trays. 
       FIG. 4  shows an assembly  100  of combinable cavity trays comprising three individual combinable cavity trays  10 . The cavities  20  (indicated by black circles) and passages  30  (indicated by white circles) of the combinable cavity trays  10  are arranged in a 3×6 matrix. Each combinable cavity tray  10  comprises six cavities  20  and twelve passages  30  such that the number of cavities  20  is smaller than the number of passages  30  by a factor of two. Each of the in total 6 rows comprise one cavity  20  and two passages  30 . Each of the in total 3 columns comprise two cavities  20  and four passages  30 . The cavities  20  of the same column are arranged such that they are never in immediate vicinity but such that there is at least one, or preferably two, passage(s) in between. The more evenly the cavities  20  of a combinable cavity trays  10  are distributed, the more stable is the structure of the combinable cavity trays  10 . Another benefit of evenly distributing the cavities  20  is that there is more material present for forming the cavities in a thermoforming process such that the cavities  20  can comprise a larger depth and therefore also a larger volume. 
       FIG. 5  shows a perspective view of a combinable cavity tray  10 . The pipetting cavities  21  and the passages  30  are arranged in an 8×12 matrix. The pipetting cavities  21  and passages  30  are arranged alternating in relation to both their arrangement in row (in total twelve) and in column (in total eight). In consequence, when viewed in column or in row, a pipetting cavity  21  is always in direct vicinity to a passage  30  but never in direct vicinity to another pipetting cavity  21 . The pipetting cavities  21  are formed integrally such that the combinable cavity tray  10 , or at least its main body, and the pipetting cavities  21  are designed in one piece. The combinable cavity tray  10 , or at least its main body, is preferably made of a thermosoftening plastic (also known as thermoplastic material; e.g. polyethylene terephthalate (PET), polystyrene (PS) or polypropylene (PP)) or a compound foil comprising thermosoftening plastic(s), and the cavities for forming the pipetting cavities  21  are preferably formed by a thermoforming process. The combinable cavity tray  10  comprises a positioning means designed as a positioning rim  43  surrounding the main body of the combinable cavity tray  10  and providing for a guiding assistance when e.g. putting a second combinable cavity tray (not shown) onto the combinable cavity tray  10  or inserting a second combinable cavity tray (not shown) into the combinable cavity tray  10 . However, such a positioning rim  43  may not only serve as positioning support but also for stabilizing the combinable cavity tray  10  and/or for providing an interface to a gripper of a liquid handling system. The pipetting cavities  21  of the shown combinable cavity tray  10  comprise a conical shape with the opening  22  showing the largest cross-sectional area and the bottom part of the pipetting cavity  21  comprising the aperture  23  showing the smallest cross-sectional area. In the shown example, the opening  22  of the pipetting cavities  21  is larger than the size of the passages  30 . Nonetheless, the predominant section of the pipetting cavities  21  comprises a cross-sectional area being small enough to fit through the cavities  30  of a comparably designed further combinable cavity tray. 
       FIG. 6 a    shows a perspective view of an assembly  100  of a first combinable cavity tray  11  and a second combinable cavity tray  12 . Both combinable cavity trays  11 ,  12  comprise  48  pipetting cavities  21  and  48  passages  30  each being arranged in an 8×12 matrix. The pipetting cavities  21  and passages  30  are arranged alternating in relation to both their arrangement in row and in column. However, the position of the pipetting cavities  21  and the passages  30  of the first combinable cavity tray  11  and the second combinable cavity tray  12  are defined complementary such that the first combinable cavity tray  11  shows a pipetting cavity  21  where the second combinable cavity tray  12  shows a passage  30 . Furthermore, the combinable cavity trays  11 ,  12  of the arrangement  100  comprise various interacting positioning means and/or interacting fixation means  50 . The second combinable cavity tray  12 , for instance, comprises a female positioning means  41  in each of its four corners designed as a positioning cavity. The first combinable cavity tray  11 , on the other hand, comprises a male positioning means  42  in each of its four corners designed as a positioning protrusion configured to interact with the female position means  41  of the second combinable cavity tray  12 . Furthermore, both combinable cavity trays  11 ,  12  comprise a positioning rim  43  surrounding the main body of the combinable cavity trays  11 ,  12 . The positioning rim  43  of the first combinable cavity tray  11  is slightly smaller in its circumference such that it can be positioned within the circumference of the positioning rim  43  of the second combinable cavity tray  12 . Even further, the combinable cavity trays  11 ,  12  comprise in total six fixation means  50  along the inside of the positioning frames  43  (only one indicated by reference number  50 ) for strongly or even irreversibly coupling the combinable cavity trays  11 ,  12  of the assembly  100 . The dashed line B-B indicates the cutting line for the sectional view of  FIG. 6   b,  the dashed line C-C indicates the cutting line for the sectional view of  FIG. 6 c    and the dashed line D-D indicates the cutting line for the sectional view of  FIG. 6   d.  The dashed rectangle indicates the section of the assembly  100  shown in  FIG. 6 e    as enlarged view. 
       FIG. 6 b    shows a sectional view along cutting line B-B of the assembly  100  of combinable cavity trays of  FIG. 6 a    with its first combinable cavity tray  11  and its second combinable cavity tray  12 . Well visible are the pipetting cavities  21  with their apertures  23  and openings  22 , as well as the passages  30  and the positioning frames  43  of the first and second combinable cavity trays  11 ,  12 . Furthermore, two of the female positioning means  41  and three of the interacting fixation means  50  are shown in side view. 
       FIG. 6 c    shows a sectional view along cutting line C-C of the assembly  100  of combinable cavity trays of  FIG. 6 a    with its first combinable cavity tray  11  and its second combinable cavity tray  12 . Well visible are the pipetting cavities  21  with their apertures  23  and openings  22 , as well as the passages  30  and the positioning frames  43  of the first and second combinable cavity trays  11 ,  12 . Compared to the sectional view of  FIG. 6   b,  the openings  22  and passages  30  have interchanged places. Furthermore, two of the female positioning means  41  and three of the interacting fixation means  50  are shown in side view. 
     By means of  FIG. 6 c    it is explained that the pipetting cavities  21  of the first and the second combinable cavity tray  11 ,  12  are designed differently such that—in assembled state—all endings of the pipetting cavities  21  are at the same height or in other words on the same level (level or height indicated as dashed line). When taking a closer look at the enlarged sectional view indicated by the dashed-lined rectangle, it becomes clear that the pipetting cavity  21  with its opening  22  of the first combinable cavity tray  11  protrudes through the passage (not labeled) of the second combinable cavity tray  12  and that the edge of the opening  22  of the pipetting cavity  21  of the first combinable cavity tray  11  rests upon the edge of the passage  30  of the second combinable cavity tray  12  (see e.g. circled area of the enlarged view). The first combinable cavity tray  11  being the top combinable cavity tray in this example is therefore positioned higher than the second combinable cavity tray  12  by the material thickness of the edge of the passage  30  of the second combinable cavity tray  12 . In order to provide for endings of the pipetting cavities  21  of the first and the second combinable cavity tray  11 ,  12  at the same level, the pipetting cavities  21  of the first—or in other words top—combinable cavity tray  11  are longer than the pipetting cavities  21  of the second—or in other words bottom or subjacent—combinable cavity tray  12  by the thickness of the material surrounding the passages  30  of the combinable cavity tray  12 . 
       FIG. 6 d    shows a sectional view along cutting line D-D of the assembly  100  of combinable cavity trays of  FIG. 6 a    with its first combinable cavity tray  11  and its second combinable cavity tray  12 . Well visible are the pipetting cavities  21  with their apertures  23  and openings  22 , as well as the passages  30  and the positioning frames  43  of the first and second combinable cavity trays  11 ,  12 . The position of the openings  22  and passages  30  is comparable to the one shown in the sectional view of  FIG. 6   b.  However, the cutting line D-D goes not only through the pipetting cavities  21  of the first and second combinable cavity tray  11 ,  12  but also through one of the female positioning means  41  and one of the male positioning means  42  interact with said female position means  41 . Another of the female positioning means  41  and three of the interacting fixation means  50  are shown in side view. The sectional view as shown makes clear that the female and male positioning means  41 ,  42  are not distributed symmetrically in the four corners but that the neighboring female and male positioning means  41 ,  42  on the right-hand side are closer to each other and therefore further away from the positioning frames  43  as the neighboring female and male positioning means  41 ,  42  on the left-hand side (please also consult  FIG. 6 a   ). Of course, this different spacing between the neighboring positioning means of opposite sides of the combinable cavity trays is not restricted to what is considered the left-hand side and right-hand side of the combinable cavity trays here. For further information, please consult  FIG. 7 . 
       FIG. 6 e    shows an enlarged view of a section of the assembly  100  of combinable cavity trays of  FIG. 6   a.  At least a part of the pipetting cavities  21  of the combinable cavity trays of the assembly  100  comprise reinforcing means  44  designed as strengthening ribs that e.g. comprise an essentially trigonal shape. These strengthening ribs can for instance be designed as bulges providing not only for additional strength of the pipetting cavities  21  but also for an enlargement of the volume for receiving fluid of the pipetting cavities  21 . 
       FIG. 7  shows a stack  110  of several assemblies  100  of combinable cavity trays according to the invention. What has already been described in connection with  FIG. 6 d    is further exemplified now. It is the different spacing between neighboring positioning means  41 ,  42  of opposite sides of the combinable cavity trays that allow the single combinable cavity trays, or in this example, the single assemblies  100  of combinable cavity trays to be stacked on top of each other when each second single combinable cavity tray, or in this example, each single second assembly  100  of combinable cavity trays of a stack  110  are rotated by 180° (e.g. around axis X as indicated in  FIG. 1 a   ,  1   b,    2   a,    2   b,    3 ). The female positioning means  41 , or in particular the depth of the female positioning means  41 , defines the distance between the single combinable cavity trays, or in this example, the distance between the single assemblies  100  of combinable cavity trays in the stack  110 . Said distance allows a gripper to pick up a combinable cavity tray or assembly  100  of cavity trays from the stack  110 . Furthermore, the female positioning means  41  prevent the single combinable cavity trays or single assemblies  100  of combinable cavity trays from sticking together when stacked. 
       FIG. 8 a    shows an assembly  100  of combinable cavity trays  10  according to the invention connected to a multichannel pipetting head  60  of a pipetting apparatus (whole pipetting apparatus not shown).  FIG. 8 b    shows a cross-sectional view thereof. The assembly  100  comprises a first combinable cavity tray  11  and a second combinable cavity tray  12 , the assembly  100  being designed e.g. like the one shown in  FIG. 6   a.  The multichannel pipetting head  60  comprises pipetting tubes  61  having a first end  62  provided with an opening for aspirating and/or dispensing of a sample fluid and a second end  63  operationally connected to a pressure generating means. The pressure in this example is transferred by plungers  64 . The first ends  62  are configured to connect to the assembly  100  by partially entering the upper region of the pipetting cavities  21 . The first ends  62  preferably comprise a conical shape further supporting a friction fit of a couple consisting of a pipetting cavity  21  and a first end  62  of a pipetting tube  61 . In order to achieve a fluid-tight, or in other words sealing, connection between pipetting tube  61  and pipetting cavity  21 , the first end  62  of the pipetting tube  61  shall be inserted in the upper region of the pipetting cavity  21  with a certain force. However, in case this certain force is rather strong, the connecting process would rather squeeze the stack providing the assembly  100  to be taken up than connecting in a sealing manner pipetting tubes  61  and pipetting cavities  21 . To prevent any squeezing, the assembly  100  can be taken up in two steps. In a first step, the first ends  62  of the pipetting tubes  61  are inserted in the upper region of the pipetting cavities  21  with little force but enough force to lift the top-most assembly  100  from the stack and provide for a friction fit. In a second step, the lifted assembly  100  is moved towards and set upon a solid base or support plate, such as a tip box. The first ends  62  of the pipetting tubes  61  are then inserted further with more force than in the first step to achieve a fluid-tight connection. The first ends  62  of the pipetting tubes  61  may comprise sealing means such as a rubber O-ring seal or alike. 
       FIG. 9  shows a method of manufacturing  200  a combinable cavity tray. The method comprises a first step of providing a sheet of at least one thermosoftening plastic  210 . In a second step, the sheet is shaped by thermoforming  220  to form at least one cavity. In a third step, at least one passage is formed into the sheet  230  for leading through a cavity of a second combinable tip tray and/or for connecting to a pipetting apparatus. 
       FIG. 10  shows a method of manufacturing  200  a combinable cavity tray. This method differs from the method of  FIG. 7  by the additional fourth step of forming at least one aperture in the bottom area of the at least one cavity  240 . The steps of providing a sheet of at least one thermosoftening plastic  210 , shaping the sheet by thermoforming  220  and forming at least one passage into the sheet  230  are identical. 
     
       
         
           
               
             
               
                   
               
               
                 Reference Signs 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 10 
                 Combinable cavity tray 
               
               
                 11 
                 First combinable cavity tray 
               
               
                 12 
                 Second combinable cavity tray 
               
               
                 20 
                 Cavity 
               
               
                 21 
                 Pipetting cavity 
               
               
                 22 
                 Opening 
               
               
                 23 
                 Aperture 
               
               
                 30 
                 Passage 
               
               
                 40 
                 Positioning means 
               
               
                 41 
                 Female positioning means 
               
               
                 42 
                 Male positioning means 
               
               
                 43 
                 Positioning rim 
               
               
                 44 
                 Reinforcing means 
               
               
                 50 
                 Fixation means 
               
               
                 60 
                 Multichannel pipetting head 
               
               
                 61 
                 Pipetting tubes 
               
               
                 62 
                 First end with opening for 
               
               
                   
                 aspirating and/or dispensing 
               
               
                 63 
                 Second end operationally connected 
               
               
                   
                 to a pressure generating means 
               
               
                 64 
                 Plunger 
               
               
                 x 
                 Axis 
               
               
                 100 
                 Assembly of combinable cavity trays 
               
               
                 110 
                 Stack of assemblies of combinable cavity trays 
               
               
                 200 
                 Method of manufacturing a combinable cavity tray 
               
               
                 210 
                 Providing a sheet of at least one 
               
               
                   
                 thermosoftening plastic 
               
               
                 220 
                 Shaping the sheet by thermoforming 
               
               
                 230 
                 Forming at least one passage into the sheet 
               
               
                 240 
                 Forming at least one aperture in the bottom 
               
               
                   
                 area of the at least one cavity