TECHNICAL FIELD

[001] The present disclosure relates to a dispensing or printing arrangement comprising a lid retaining system for handling a sample container with lid, and to a method of de-lidding and lidding a sample container using the lid retaining system.

BACKGROUND ART

[002] 3D bioprinting is based on a process in which a biomaterial can be deposited layer-by-layer using a 3D bioprinter. Biomaterials such as hydrogels or other polymers can be combined with cells and growth factors to imitate natural tissues. The technology is used in the fields of bioengineering and medicine. The 3D bioprinter is capable of extruding material with or without cells while moving in three directions, which enables the building of complex structures. It offers unlimited possibilities in applications from drug screening to organ regeneration.

[003] Sterility is a critical factor in bioprinting and biodispensing applications and can greatly affect the results of studies, experiments, and assays dealing with bioprinted media and the cells within them. Contamination of any form, such as the introduction of unwanted bacterial, viral, or cross-contamination involving outside cellular material such as skin cells, or even unwanted biomaterial, such as gelatin methacrylate, collagen, or other typical biomaterials will completely invalidate the results of such studies. For this reason, minimizing human interaction with biological sample containers into/onto which bioprinting or biodispensing actions are performed is necessary before, after and during such actions. For example, reducing or removing human interaction with the sample container during removal and replacement of the protective lid of a container before and after a dispensing/printing action is necessary.

[004] A lid retaining system holds the lid of a biological sample container away while actions are being performed on the sample container. Once those actions are complete, the lid is returned to the container. The lid retaining system limits human interaction with the container, thereby preventing possible contamination issues during biological studies. [005] A lid retaining system is for example described in EP2788033B1, which discloses a system comprising means for removing a well plate lid for example using suction, gluing, articulated arms, fasteners, magnets, and electromagnets.

[006] Another lid retaining system is shown in US6998094B2, which discloses an apparatus for handling biological sample containers each having a lid. The apparatus comprises a conveyor assembly operable to convey containers between a first position and a second position, and a lid handling assembly operable to remove lids from containers being conveyed through the lid handling assembly from the first position to the second position, and to replace the lids onto containers being conveyed through the lid handling assembly from the second position to the first position. Lid removal and replacement being effected by mechanical interaction between the lids and the lid handling assembly as the containers are conveyed through the lid handling assembly.

SUMMARY OF THE INVENTION

[007] It is an object of the present disclosure to provide an improved or at least an alternative lid retaining system for handling a sample container with lid in a dispensing or printing arrangement. A further object is to provide a method of de-lidding and lidding a sample container using the lid retaining system.

[008] The invention is defined by the appended independent patent claims. Nonlimiting embodiments emerge from the dependent patent claims, the appended drawings and the following description.

[009] According to a first aspect there is provided a dispensing or printing arrangement comprising an apparatus for handling a sample container having a lid, the apparatus comprising a housing, a carrier operable to bring a sample container from a first position to a second position arranged in the housing, and a lid retaining system arranged or arrangeable at the second position in the housing and arranged to grip a lid of the sample container when the sample container is in the second position. The lid retaining system comprises a first and second gripping member, each gripping member being provided with a gripping surface. The system further comprises a support arm, wherein the first and second gripping members are moveably connected relative to each other by the support arm. The first and second gripping members are arranged to, in a first position relative to each other, grip a sample container lid between the two gripping surfaces, such that the gripping surfaces abut against a peripheral edge/peripheral edges of the lid substantially perpendicular to a major surface of the lid. The first and second gripping members are arranged to when moved away from each other from the first position towards a second position, release a lid being gripped between the two gripping surfaces in the first position. A drive unit is operatively connected with the support arm and arranged to via the support arm move the first and second gripping members relative to each other between the first and second position. A lid detection mechanism is arranged to detect if/when a lid is gripped between the first and second gripping surfaces of the gripping members. A processor is arranged to receive a signal from the lid detection mechanism of the lid retaining system when a lid is gripped between the first and second gripping surfaces, and when such a signal has been received arranged to actuate a movement of the carrier and/or at least a portion of the lid retaining system such that the lid and the sample container are separated and moved from each other. The dispensing or printing arrangement further comprising a dispensing system or printing system arranged or arrangeable in the housing. [0010] The lid retaining system grips and holds the lid of a sample container, such as a biological sample container, for example a petri dish or a well plate. Thereby, it is possible to separate the container and the lid from each other as the lid is held by the lid retaining system, such that actions, e.g. a biodispensing or bioprinting action, may be performed onto/into the sample container.

[0011] The lid retaining system eliminates human interaction with the container and lid such as before and after a printing/dispensing action into/onto the sample container, and thereby eliminates possible contamination through human error. The lid retaining system also simplifies processing by automatically handling lidding and de-lidding operations [0012] The lid detection mechanism is arranged to detect if/when a lid is gripped between the first and second gripping surfaces. This information may be used to tell that the container and lid are ready to be moved/separated from each other. The lid detection mechanism could also be used to stop actuation of the gripping members once a lid has been detected.

[0013] Due to the lid detection mechanism, containers of a wide variety of sizes can be inserted in the lid retaining system and without crushing the lids.

[0014] Detection of the presence of a lid may be used in the system and may also be communicated to a user of the system. [0015] When the container and lid has been separated and moved from each other, actions may be performed onto/into the sample container, such as dispensing or printing actions.

[0016] The housing may be comprise a clean, sterile environment, or at least a sterilized environment.

[0017] When dispensing or printing actions have been completed, the carrier and/or the at least a portion of the lid retaining system are actuated such that that the lid and the container are moved towards each other and aligned such that the lid can be released from the lid retaining system and put back on the container again, protecting it from contamination. Thereafter, the container with lid is moved back to the first position by means of the carrier.

[0018] The drive unit may be selected from an electromagnetic, a pneumatic, a hydraulic, and an inductive drive unit

[0019] The lid detection mechanism may be selected from one or more of a vacuum probe, a touch sensitive sensor, a distance measuring sensor, a vision-based sensor and a force measuring mechanism.

[0020] The lid detection mechanism may comprise one or several of the listed detection mechanisms.

[0021] The lid detection mechanism may be a force measuring mechanism and comprise the drive unit, the support arm and the gripping members, wherein a force needed by the drive unit to move the two gripping members from the second position towards the first position is registered, and a change in the registered force indicates that a lid has been gripped between the two gripping surfaces.

[0022] This embodiment utilizes a feedback system for detecting the presence of a lid. The drive unit may be an electromagnetic drive unit and the feedback registered may be a back electromotive force. When resistance increases, the electromotive force of the drive unit changes, indicating the presence of an object/lid. This detected presence may send a signal to trigger drive unit power cut-off. This closed-loop feedback system can be used alone or together with one or more of the other lid detection mechanisms mentioned above.

[0023] The support arm may be a thread driven rod or a gear driven rod.

[0024] The dispensing or printing arrangement may be a biodispensing or bioprinting arrangement. [0025] The dispenser/printing system may be a 3D biodispensing/3D bioprinting system arranged in the housing.

[0026] In 3D bioprinting a biomaterial can be deposited layer-by-layer using a 3D bioprinter. Biomaterials such as hydrogels or other polymers can be combined with cells and growth factors to imitate natural tissues.

[0027] The 3D bioprinter is capable of extruding material with or without cells while moving in three directions, which enables the building of complex structures.

[0028] Sterility or keeping a sterilized environment is a critical factor in biodispensing/bioprinting applications and can greatly affect the results of studies, experiments, and assays dealing with bioprinted media and the cells within them. Contamination of any form such as the introduction of unwanted bacterial, viral, or crosscontamination involving outside cellular material such as skin cells, or even unwanted biomaterial, such as gelatin methacrylate, collagen, or other typical biomaterials will completely invalidate the results of such studies. With the present biodispensing/bioprinting arrangement comprising the automatic lid retaining system, human interaction with sample containers during the removal and replacement of the protective lid is avoided. Thereby, a sterile or a sterilized environment can be maintained in the housing.

[0029] According to a fourth aspect there is provided a method of de-lidding and lidding a sample container. The method comprises: at a first position to load a sample container with lid onto a carrier; by means of the carrier transporting the sample container to a second position within a housing; by means of the lid retaining system described above and arranged at the second position in the housing, grip the lid of the sample container. Upon detection of a signal that a lid is gripped by the lid retaining system, actuate a movement of the carrier and/or at least a portion of the lid retaining system such that the lid and the container are separated and moved from each other; optionally performing a dispensing or printing action into/onto the container; by means of the carrier and/or at least a portion of the lid retaining system aligning the lid and the container in the second position; releasing the lid from the lid retaining system such that the lid is placed back onto the sample container, and by means of the carrier moving the lidded container to the first position.

BRIEF DESCRIPTION OF THE DRAWINGS [0030] Fig. 1 shows an embodiment of a lid retaining system where gripping members clamp onto the sides of a petri dish lid.

[0031] Fig. 2 shows an embodiment of a lid retaining system where the gripping members clamp onto the sides of a well plate lid.

[0032] Fig. 3 shows an embodiment of a lid retention system where the gripping members are actuated by a screw driven by an electromagnetic motor.

[0033] Figs 4 and 5 demonstrate the lid retention system shown in any of Figs 1-3 in an apparatus for handling a sample container, such as in a biodispensing or bioprinting arrangement.

[0034] Fig. 6 schematically illustrates a method of de-lidding and lidding a sample container.

DETAILED DESCRIPTION

[0035] Sterility or keeping a sterilized environment is a critical factor in bioprinting and biodispensing applications, why minimizing human interaction with biological sample containers into/onto which bioprinting or biodispensing actions are performed is necessary before, after and during such actions.

[0036] A lid retaining system holds the lid of a biological sample container away while actions, such a biodispensing or bioprinting, are being performed into/onto the sample container. Once those actions are complete, the lid is returned to the container. The lid retaining system limits human interaction with the container, thereby preventing possible contamination issues.

[0037] In Figs 1-3 are shown a lid retaining system 1 for handling a sample container 100 with lid 101. The sample container may be a biological sample container such as a petri dish (Fig. 1) or a well plate (Fig. 2).

[0038] The lid retaining system 1 comprises a first and second gripping member 2a, 2b, wherein each gripping member is provided with a gripping surface. The gripping members 2a, 2b are moveably connected relative to each other by a support arm 3, 3'.

[0039] The gripping surfaces may at least partially comprise a friction material such as rubber or silicon and/or comprise a friction enhancing pattern/surface structure. The gripping surface may be constituted by a portion of the gripping member 2a, 2b. Alternatively, the gripping surface is a separate member attached to a portion of the gripping member 2a, 2b by means of for example gluing, nailing or welding. Each gripping member may comprise at least one gripping surface. In some embodiments each gripping member 2a, 2b comprises two or more gripping surfaces or gripping surface portions. A gripping surface may be a continuous gripping surface or may comprise two or more distinct gripping surface portions. The system may comprise two or more gripping members 2a, 2b, such as three or four gripping members connected to each other through the support arm 3, 3'. Both gripping members 2a, 2b may be moveable. Alternatively, only one of the gripping members is moveable, but still moveable relative to each other.

[0040] The support arm 3, 3'may comprise a support arm assembly comprising two or more connected support arm entities. The support arm may be a thread driven rod or a gear driven rod actuated by a drive unit 4.

[0041] The first and second gripping members 2a, 2b are arranged to, in a first position relative to each other, grip a sample container lid 101 (see Figs 1 and 2) between the two gripping surfaces, such that the gripping surfaces abut against a peripheral edge/peripheral edges of the lid 101 substantially perpendicular to a major surface of the lid 101.

[0042] The first position of the gripping members 2a, 2b relative to each other may be determined by the dimensions of the container/lid. When a lid has been gripped between the two gripping surfaces, the first position is reached. Alternatively, the first position can be determined by user input into the system 1 on container type/size.

[0043] The gripping surfaces are arranged to mainly abut against the peripheral edge(s) of the container 100. In some embodiments, a portion of the gripping surfaces may also abut against a major surface of the sample container 100.

[0044] The first and second gripping members 2a, 2b are arranged to when moved away from each other from the first position towards a second position, release a lid 101, which was gripped between the two gripping surfaces in the first position. Before the lid 101 is released, the lid 101 and the container 100 are preferably aligned by the system 1 such that the lid is correctly placed back onto the sample container. A position of the lid gripping members 2a, 2b and the container 100 may be registered by a processor of the system. The processor may actuate the movement of the lid and/or the container such that the lid can be correctly put back onto the container after a printing/dispensing action is finished. [0045] The second position of the two gripping members 2a, 2b relative to each other may be at a fixed distance from each other. Alternatively, the second position may vary and depend on predetermined or measured factors such as container size etc.

[0046] When the lid retaining system 1 is in a waiting mode, i.e. there is no container in the system, the gripping members 2a, 2b, may be brought to/waiting in the first position relative to each other, in the second position relative to each other, in any position in between the first and second position, or in a position wherein the two gripping members 2a, 2b are closer to each other than when in a first position relative to each other. The drive unit 4 may actuate the gripping members 2a, 2b when a container reaches the lid retaining system 1 and the gripping members 2a, 2b are then brought into a position such that the lid can be gripped between the gripping surfaces. When a container with lid approaches the lid retaining system the gripping members may be brought into the second position relative to each other. This second position being determined for example by known dimensions of the container or by means of distance sensors etc. In one embodiment a start position/waiting mode position of the gripping members 2a, 2b can be measured using for example an endstop. Alternatively, the start position/waiting mode position of the two gripping members 2a, 2b can be determined by means of a distance sensor or an encoder on a shaft of the drive unit 4.

[0047] The drive unit 4 is operatively connected with the support arm 3, 3' and arranged to via the support arm 3, 3' move the first and second gripping members 2a, 2b relative to each other between the first and second position.

[0048] The drive unit 4 may be selected from an electromagnetic, a pneumatic, a hydraulic, and an inductive drive unit.

[0049] The lid retaining system 1 also comprises a lid detection mechanism 5 arranged to detect if/when a lid 101 is gripped between the first and second gripping surfaces of the gripping members 2a, 2b. This information may be used to tell that the container 100 and lid 101 are ready to be moved/separated from each other. The lid detection mechanism 5 could also be used to stop actuation of the gripping members 2a, 2b once a lid has been detected. Due to the lid detection mechanism 5, containers 100 of a wide variety of sizes can be inserted in the lid retaining system 1 and without crushing the lids. Detection of the presence of a lid 101 may be used in the system 1 and may also be communicated to a user of the system. [0050] The lid detection mechanism 5 may be selected from one or more of a vacuum probe, a touch sensitive sensor, a distance measuring sensor, a vision-based sensor and a force measuring mechanism.

[0051] A vacuum-based probe may be arranged such that it can be moved until it encounters an object, the gripped lid, and then would draw vacuum. Most container lids are flat and smooth and made from either glass or plastic. If the probe was to encounter a lid surface, a vacuum would be registered, indicating the presence of a lid.

[0052] A touch sensitive sensor or a distance measuring sensor, such as an end-stop, switch, time-of-flight, laser, lidar, optical, inductive, magnetically actuated, or infrared sensor may be used to detect the lid. Such sensors may for example be arranged in contact with or in vicinity of the first and/or second gripping member.

[0053] A vision-based sensor would test for the presence of lids using algorithms that test for certain edge differences or differences between reflective surfaces. There are many different conditions to test for with an adaptable vision sensor that could be used to determine the presence of a lid.

[0054] A force measuring lid detection mechanism may measure a force needed for moving the gripping members 2a, 2b towards the first position, wherein a change in force indicates that a lid has been gripped between the gripping surfaces. Such a force measuring mechanism 5 may comprise the drive unit 4, the support arm 3 and the gripping members 2a, 2b. A force needed by the drive unit 4 to move the two gripping members 2a, 2b from the second position towards the first position is registered and a change in the registered force indicates that a lid 101 has been gripped between the two gripping surfaces.

[0055] This embodiment utilizes a feedback system for detecting the presence of a lid 101. The drive unit 4 may be an electromagnetic drive unit and the feedback registered may be a back electromotive force. When resistance increases, the electromotive force of the drive unit changes, indicating the presence of an object/l id . This detected presence may send a signal to trigger drive unit power cut-off. This closed-loop feedback system can be used alone or together with one or more of the other lid detection mechanisms.

[0056] With the above described lid retaining system 1, it is possible to separate the container 100 and the lid 101 from each other as the lid 101 is held by the lid retaining system 1, such that actions, e.g. a biodispensing or bioprinting action, may be performed onto/into the sample container 100. The lid retaining system 1 eliminates human interaction with the container 100 and lid 101 before and after a bioprinting/biodispensing action into/onto the sample container, and thereby eliminates possible contamination through human error. The lid retaining system 1 also simplifies processing by automatically handling lidding and delidding operations.

[0057] As is illustrated in Figs 4 and 5, the lid retaining system may be integrated in an apparatus 10 for handling a sample container 100 having a lid 101. A dispensing or printing arrangement 30 may comprise the apparatus 10 and further a dispensing system or printing system 31 arranged in a housing 22 of the apparatus 10.

[0058] The apparatus 10 comprises a housing 22 and a carrier 21 operable to bring a sample container from a first positon to a second position arranged in the housing 22. The housing may be comprise a clean, sterile or sterilized environment. The second position is arranged inside the housing. The first position may be arranged outside the housing (as illustrated in Figs 4, 5) or inside the housing 22. Preferably, the first position is arranged outside the housing 22 and the carrier 21 arranged to bring the container 100 from the first position outside the housing into the housing and to the second position.

[0059] The lid retaining system 1 may be arranged at the second position in the housing 22 and arranged to grip a lid 101 of the sample container 100 when the sample container 100 is in the second position. The lid retaining system 1 may be stationary. Alternatively, at least a portion thereof could be moveable relative the container 100, for example by use of a gantry system.

[0060] A processor is arranged to receive a signal from the lid detection mechanism 5 of the lid retaining system 1 when a lid 101 is gripped between the first and second gripping surfaces, and when such a signal has been received arranged to actuate a movement of the carrier 21 and/or at least a portion of the lid retaining system 1 such that the lid 101 and the sample container 100 are separated and moved from each other.

[0061] When the container 100 and lid 101 has been separated and moved from each other, actions may be performed on the sample container, such as dispensing or printing actions. Such actions may take place at the second position in the chamber (if the lid retaining system 5 with gripped lid 101 is moved away from the second position). Alternatively, such actions may take place at a third position within the housing 22, spatially separate from the second position, to which position the sample container 100 has been moved by the carrier 21 after the lid has been gripped by the gripping members 2a, 2b. The container 100 being moved to the third position by means of the carrier 21.

[0062] When dispensing or printing actions, for example by means of a 3D biodispensing/3D bioprinting system arranged in the housing 22, have been completed, the carrier 21 and/or the lid retaining system 5 are actuated such that that the lid 101 and the container 100 are moved towards each other and aligned such that the lid can be released from the lid retaining system and put back on the container again, protecting it from contamination. Thereafter, the container 100 with lid 101 is moved back to the first position by means of the carrier 21.

[0063] Sterility or keeping a sterilized environment is a critical factor in biodispensing/bioprinting applications. With the present biodispensing/bioprinting arrangement 30 comprising the automatic lid retaining system 5, human interaction with sample containers 100 during the removal and replacement of the protective lid 101 is avoided.

[0064] In Fig. 6 is a method of de-lidding and lidding a sample container 100 illustrated. The method comprises to load 300 a sample container 100 with lid 101 onto a carrier 21 at a first position. By means of the carrier 21, the sample container 100 is transported 301 to a second position within a housing 22. By means of the lid retaining system 1 described above and arranged at the second position in the housing 22 the lid 101 of the sample container 100 is gripped 302. Upon detection 303 of a signal that a lid 101 is gripped by the lid retaining system 1, a movement of the carrier 21 and/or at least a portion of the lid retaining system 1 is actuated 304 such that the lid 101 and the container are separated and moved from each other. Optionally, a dispensing or printing action 305 is performed into/onto the container 100. By means of the carrier 21 and/or at least a portion of the lid retaining system 1 the lid 101 and the container 100 are aligned 306 in the second position. Thereafter, the lid 101 is released 307 from the lid retaining system 5 such that the lid 101 is placed back onto the sample container 100, and by means of the carrier 21 the lidded container 100 is moved 308 to the first position.