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 cm2 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 cm2.
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:
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.
By means of
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19215078 | Dec 2019 | EP | regional |
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Number | Date | Country | |
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20210178400 A1 | Jun 2021 | US |