# Patent

## Title
System for processing closed sample tubes

## Abstract

A system for processing sample tubes comprising biological samples is presented. The system comprises two or more work cells for processing samples. In conjugation with at least two of the work cells, the system comprises one of the following units: a pipetting unit for withdrawing a volume of sample from a sample tube to be processed by the work cell and/or dispensing a volume of liquid into the sample tube, and an analytical unit for determining at least one sample parameter of a sample contained in a sample tube. The system further comprises a decapping/recapping device for each of the at least two work cells for removing a closure from a sample tube and for reclosing the sample tube before it is transported to another work cell.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of EP 11170619.8, filed Jun. 20, 2011, which is hereby incorporated by reference.
BACKGROUND
The present disclosure generally relates to in vitro diagnostics and, in particular, to a system for processing sample tubes comprising a plurality of work cells for processing samples and to a method of processing sample tubes comprising withdrawing a volume of sample from a tube to be processed by the work cell and/or dispensing a volume of liquid into the sample tube.
Coming from diverse healthcare facilities, biological samples such as blood samples usually arrive in the laboratories in different kinds of tubes with various types of closures. These are typically primary sample tubes, so called because they are used to collect the samples, for example, by venipuncture.
There are instruments, which may process primary sample tubes without the need to remove the closure, i.e., by accessing the sample contained in the primary tube by piercing the closure with a pipetting needle, for example. Not all closures however are suitable for this procedure and not all types of instruments and/or analysis allow the use of this procedure. Some types of instruments and/or analysis require the primary tubes to be opened before samples are pretreated and/or analyzed. Therefore, such instruments should have an automatic decapper to automatically remove the closure from a primary tube.
Automated decapping of test tubes can be complicated by the variety of available primary tubes, which may vary in diameter, height, and especially the variety of available closures. Some closures have, for example, a thread for screwing on primary tubes. Another type of closure is a rubber stopper or cap, which may be removed by a pulling motion. The closures may also differ in their composition. They may be made of rubber, plastic, etc. Decapping devices that can decap, i.e., remove closures from, all or most of these types of primary tubes have been developed and are available on the market. These are typically modules integrated in a pre-analytical work cell, wherein one or more aliquots of a sample are withdrawn from a sample tube and transported in secondary tubes to one or more analytical work cells for being processed. The sample tube is then optionally reclosed either with the same closure or a new closure.
One alternative approach is to open the primary sample tube in a pre-analytical work cell and to dispose the original closure, to transport the opened tube to one or more analytical work cells for being processed and then to reclose the tube with a new closure, typically in a post-analytical work cell. One general problem is that the sample processing throughput is limited by the decapping and/or recapping throughput of the pre-analytical work cell.
Therefore, there is a need to increase sample processing throughput in a system comprising a plurality of work-cells enabling the opening, pipetting and reclosing to be more independent without the need for additional closures and without severe limitations on processing with a reduction of the costs and size of the decapping/recapping device allowing for a plurality of such devices in the same system.
SUMMARY
According to the present disclosure, a system for processing sample tubes comprising biological samples is disclosed. The system can comprise two or more work cells for processing samples. In correspondence to at least two of the work cells, the system can comprise at least one of the following units: a pipetting unit for withdrawing a volume of sample from a sample tube to be processed by the work cell and/or dispensing a volume of liquid into the sample tube and an analytical unit for determining at least one sample parameter of a sample contained in a sample tube. The system can further comprise a decapping/recapping device for each of the at least two work cells for removing a closure from a sample tube and for reclosing the sample tube before it is transported to another work cell.
In accordance with one embodiment of the present disclosure, a method for processing sample tubes is disclosed. A sample tube closed by a closure is transported to a first work cell. The closure is removed from the sample tube with a first decapping/recapping device in correspondence to the first work cell. At least one aliquot of sample is withdrawn from the sample tube with a pipetting unit in correspondence to the first work cell for being processed by the first work cell and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter with at least one analytical unit in correspondence to the first work cell. The sample tube is reclosed with a closure with the first decapping/recapping device. The sample tube closed by the closure is transported to a second work cell. The closure from the sample tube is removed with a second decapping/recapping device in correspondence to the second work cell. At least one aliquot of sample is withdrawn from the sample tube with a pipetting unit in correspondence to the first work cell for being processed by the first work cell and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter of the sample with of at least one analytical unit in correspondence to the first work cell.
Accordingly, it is a feature of the embodiments of the present disclosure to increase sample processing throughput in a system comprising a plurality of work-cells enabling the opening, pipetting and reclosing to be more independent without the need for additional closures and without severe limitations on processing with a reduction of the costs and size of the decapping/recapping device allowing for a plurality of such devices in the same system. Other features of the embodiments of the present disclosure will be apparent in light of the description of the disclosure embodied herein.



BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
The following detailed description of specific embodiments of the present disclosure can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
FIG. 1 illustrates schematically a system for processing sample tubes comprising a plurality of work cell according to an embodiment of the present disclosure.
FIG. 2a illustrates a perspective view of a pipetting system comprising a decapping/recapping device according to an embodiment of the present disclosure.
FIG. 2b illustrates a magnification of the decapping/recapping device shown in FIG. 2a wherein some parts have been removed for clarity according to an embodiment of the present disclosure.
FIG. 3a illustrates one of the plurality of closure holders as illustrated in FIGS. 2a and 2b according to an embodiment of the present disclosure.
FIG. 3b illustrates the closure holder of FIG. 3a wherein part of the housing has been removed for making some of the inner components visible according to an embodiment of the present disclosure.
FIG. 3c illustrates a further detail into the working principle of the closure holder of FIGS. 3a and 3b according to an embodiment of the present disclosure.
FIG. 3d illustrates a bottom view of the closure holder of FIG. 3a according to an embodiment of the present disclosure.
FIG. 4 illustrates an actuator with some parts removed to reveal some inner components according to an embodiment of the present disclosure.
FIG. 5a illustrates a carousel-like rotor carrying a plurality of closure holders as illustrated in FIGS. 2a and 2b according to an embodiment of the present disclosure.
FIG. 5b illustrates a partially cut view of the carousel of FIG. 5a according to an embodiment of the present disclosure.
FIG. 6 illustrates a top view of the system of FIG. 2a wherein some parts have been removed for clarity according to an embodiment of the present disclosure.
FIGS. 7a-b illustrate in perspective from top and bottom respectively how an actuator and a passive closure gripper are being engaged (some parts removed for clarity) according to an embodiment of the present disclosure.
FIG. 7c illustrates shows the actuator and passive closure gripper of FIGS. 7a and 7b already engaged (some parts removed for clarity) according to an embodiment of the present disclosure.
FIG. 8 illustrates a tube gripper in more detail according to an embodiment of the present disclosure.
FIG. 9a illustrates a perspective view of a decapping/recapping device according to another embodiment of the present disclosure.
FIG. 9b illustrates a pipetting system comprising the decapping/recapping device of FIG. 9a according to an embodiment of the present disclosure.
FIG. 9c illustrates the same pipetting system of FIG. 9b from another perspective according to an embodiment of the present disclosure.
FIG. 9d illustrates a top view of the same pipetting system of FIGS. 9b and 9c according to an embodiment of the present disclosure.
FIG. 10 illustrates a top view of a decapping/recapping device according to yet another embodiment of the present disclosure.



DETAILED DESCRIPTION
In the following detailed description of the embodiments, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration, and not by way of limitation, specific embodiments in which the disclosure may be practiced. It is to be understood that other embodiments may be utilized and that logical, mechanical and electrical changes may be made without departing from the spirit and scope of the present disclosure.
A “sample tube”, herein interchangeably referred to also as “tube”, can be either a sample collection test tube, also called “primary tube”, which can be used to receive a sample such as a blood sample from a patient and to transport the sample contained therein to an analytical laboratory for diagnostics purposes, or a “secondary tube”, which may be used to receive an aliquot of sample from a primary tube. A primary sample tube can typically be made of glass or plastics, can have a closed end and an open end closed by a closure, which may be of different materials, assume different shapes and colors, typically associated with the type of tube, i.e., the type of sample therein or the type of conditions the sample therein is subjected to. There are for example tubes containing an anticoagulant or a coagulation inducing agent, there are tubes containing gels facilitating the separation of plasma, etc. Different types of primary tubes can often be just the result of customization of different primary tube manufacturers. Most often they reflect the type of sample and or analysis they are destined for. In particular, there are primary tubes of different size that is of different diameter and/or different height for receiving different amounts of samples. A single laboratory and typically a single instrument can therefore be required to be able to handle different types of primary tubes with possibly different types of closures. A secondary tube can typically be made of plastics and may have a lower degree of variation of size and type with respect to primary tubes. In particular, secondary tubes may be smaller than primary tubes and be designed to be closed with one type or similar types of closure, e.g., the screw type.
The term “closure” can herein be used to indicate any type of cap, comprising screw-type caps and rubber stoppers, which can be opened and/or closed by a pulling/pushing and/or screwing motion respectively.
A “work cell” can be either a stand-alone apparatus or a module within a larger instrument assisting users with sample processing. “Sample processing” can mean either detection, e.g., qualitative and/or quantitative evaluation of samples for diagnostic purpose, and/or sorting and/or preparation of samples before detection, or storing and/or disposal of samples after detection. In particular, a work cell may be related to analytical and/or to pre-analytical and/or to post-analytical sample processing steps. Work-cells may connected to each other and depend at least in part on each other, e.g., each carrying out a dedicated task of a sample processing workflow, which may be a prerequisite before proceeding to the next work-cell. Alternatively, work cells may work independently from each other, e.g., each carrying out a separate task, e.g., a different type of analysis on the same sample or different sample.
An “analytical work cell” can either be a stand-alone apparatus or module within a larger instrument assisting users with the detection, e.g., qualitative and/or quantitative evaluation of samples for diagnostic purpose. It may comprise a process and detection system whose workflow can optimized be for certain types of analysis. Examples of such work cells can be clinical chemistry analyzers, coagulation chemistry analyzers, immunochemistry analyzers, urine analyzers, used to detect the result of chemical or biological reactions or to monitor the progress of chemical or biological reactions. An analytical work cell may comprise units assisting with the pipetting, dosing, and mixing of samples and/or reagents. The work cell may comprise a reagent holding unit for holding reagents to perform the assays. Reagents may be arranged for example in the form of containers or cassettes containing individual reagents or group of reagents, placed in appropriate receptacles or positions within a storage compartment or conveyor. It may comprise a reaction vessel or cuvette feeding unit. In particular, it may comprise one or more liquid processing units, such as a pipetting unit, to deliver samples and/or reagents to the reaction vessels. The pipetting unit may comprise a reusable washable needle, e.g., a steel needle, or disposable pipette tips. The work cell may further comprise one or more mixing units, comprising e.g., a shaker to shake a cuvette comprising a liquid or a mixing paddle to mix liquids in a cuvette or reagent container.
A “pre-analytical work cell” can either be a standalone apparatus or module within a larger instrument assisting users with the sorting and/or preparation of samples before being processed by an analytical work cell. It may comprise for example one or more of the following: a resorting unit to sort samples according to type of analysis and/or priority of analysis, a centrifuge for centrifugating sample tubes, an aliquoting unit wherein a pipetting unit is used to aliquot samples from sample tubes, a thermal treatment unit to subject the sample to a certain temperature, a separation unit to separate sample components, etc.
A “post-analytical work cell” can either be a standalone apparatus or module within a larger instrument assisting users with the storing and/or disposal of samples after being processed by an analytical work cell. It may comprise for example a resorting unit to resort sample tubes, e.g., to different storage racks, and/or a refrigerated compartment.
In general, a work cell may comprise units for loading and/or unloading and/or transporting and/or storing sample tubes or racks comprising sample tubes, units for loading and/or unloading and/or transporting and/or storing reagent containers or cassettes, units for loading and/or unloading and/or transporting and/or storing and/or washing reagent vessels, e.g., cuvettes, units for loading and/or unloading and/or transporting and/or storing pipette tips or tip racks. It may comprise identification units comprising sensors, e.g., barcode or RFID readers. The instrument may further comprise one or more incubation units for maintaining sample/reagent mixtures at a certain temperature during reaction, wash stations for washing pipette tips or needles or reaction vessels, e.g., cuvettes, mixing paddles, etc.
A “pipetting unit” can be a device assisting the user with the automatic withdrawing of volumes of samples from sample tubes and/or dispensing a volume of another liquid, such as a reagent or diluting buffer, into a sample tube or reaction vessel. The pipetting unit may comprise one or more reusable washable needle, e.g., a steel needle, or use disposable pipette tips. The pipetting unit may be mounted to a transfer head that can be moved in one or two directions of travel in a plane, e.g., with guiding rails and a third direction of travel orthogonal to the plane, e.g., with a spindle drive. “In correspondence to” can mean that the pipetting unit may be integrated, i.e., built in a work-cell or be a module of the system operatively connected to a work-cell and/or to a decapping/recapping device.
An “analytical unit” can be a device for determining at least one sample parameter, such as a physical, chemical or biological parameter of a sample contained in a sample tube, normally without the addition of a reagent. The analytical unit may be for example a sensor for determining a physical parameter of the sample, such as pH, temperature, color, turbidity, viscosity, or quantity, e.g., volume, or liquid level of the sample within the tube. It may comprise for example an optical detector or a probe to be dipped at least partially into the sample. It may e.g., determine chemical or biological parameters such as analytes contained in the sample by photometric measurement or other physical techniques making use for example of ion selective electrodes or reagent coated strips subject to color change, etc. “In correspondence to” can mean that the analytical unit may be integrated, i.e., built in a work-cell or be a module of the system operatively connected to a work-cell and/or to a decapping/recapping device.
A “decapping/recapping device” can either be a standalone apparatus or module within the system and assisting the user with the automatic opening and reclosing of sample tubes when and where a sample needs to be withdrawn and/or a liquid needs to be dispensed and/or a sample parameter needs to be determined and for reclosing the sample tube before it is transported to another work cell. The decapping/recapping device may remove closures of any type from sample tubes of any type and may reclose the sample tubes with the same original closures or with new closures. It may be integrated, i.e., built in a work cell, or operatively connected to a work cell.
According to one embodiment, the decapping/recapping device can reclose sample tubes with the same original closures and can comprise at least one closure holder, each comprising a closure gripper for gripping and holding a closure, e.g., while a volume of sample is withdrawn and/or a volume of liquid is dispensed and/or a sample parameter is determined. The device may further comprise at least one tube gripper cooperating with the closure gripper for biasing a tube and its closure away from each other when removing the closure and for biasing the tube and the closure towards each other when reclosing the tube with the original closure.
A “closure holder” can be a device capable of holding a closure for a period of time between decapping, i.e., removal of that closure from a sample tube, and either disposal of that closure or recapping, i.e., reclosing of the same sample tube with that same respective closure. Each closure holder can comprise a closure gripper, which securely holds a closure by frictional pressure applied to the outside of a closure, preventing the closure to move and/or to fall.
According to one embodiment, the closure gripper can be passive and the decapping/recapping device can further comprise at least one actuator for actuating the passive closure gripper when removing a closure from a tube or reclosing a tube with its respective closure.
According to one embodiment, the decapping/recapping device can comprise a plurality of individual closure holders, each comprising a passive closure gripper for holding a closure.
According to one embodiment, the actuator can be coupled to the passive closure gripper of the closure holder when a closure is removed from a sample tube or when a sample tube is reclosed with its respective closure and can be decoupled from the passive closure gripper when the closure holder is holding a closure.
“Passive” can mean that there is a force or energy transfer between the passive closure gripper and other parts of the device, such as an actuator, only when removing a closure from a sample tube or disposing a closure or reclosing a sample tube with its respective closure and there is no force or energy transfer between the passive closure gripper and the actuator during the period of time between decapping and disposal or recapping, the force required for holding the closure during this period of time can be resilient and internal to the passive closure gripper itself. Thus, a closure gripper can be passive in the sense that it may need to be coupled with an actuator when decapping or recapping takes place but cannot perform such actions without being coupled to an actuator.
An “actuator” can be a device for actuating, i.e., transferring force or energy to the passive closure gripper when removing a closure from a tube or reclosing a tube with its respective closure. The actuator can be coupled to a passive closure gripper of a closure holder when a closure is removed from a tube or when a tube is disposed or reclosed with its respective closure and can be decoupled from a passive closure gripper when the closure holder is holding a closure. According to one embodiment, the force can be an axial force, transferred to the passive closure gripper by applying a positive or negative pressure, e.g., by pushing or pulling a passive element of the passive closure gripper. The force may also or in addition be rotational, transferred to the passive closure gripper by coupling to rotational drive. The force may be however also induced, i.e., without physical contact, e.g., magnetic.
“Coupled to” or “in coupling connection”, when referring to the relationship between an actuator and a passive closure gripper, can mean that an actuator is engaged with a passive closure gripper and a transfer of force from the actuator to the passive closure gripper can be enabled. Engagement may occur by physical contact and/or alignment. “Decoupled from” can mean that the actuator and the passive closure gripper are disengaged, i.e., physically separated from each other or misaligned. Alternatively, the actuator and the passive closure gripper may still be in physical contact or aligned but the transfer of force from the actuator to the passive closure gripper can be disabled, meaning that there is anyway no force or energy transfer from the actuator to the passive closure gripper.
It can thus be possible to alternately couple a plurality of closure holders to one or more actuators. According to a one embodiment, one or more actuators can be fixed within the device while a plurality of closure holders can move with respect to the fixed actuators such as to be in turn coupled to the at least one actuator. The opposite can also be possible, wherein a plurality of closure holders can be fixed and one or more actuators can move with respect to the fixed closure holders.
The decapping/recapping device further can comprise at least one tube gripper cooperating with the at least one closure holder and/or actuator for biasing a tube and its closure away from each other when removing the closure and for biasing the tube and its closure towards each other when reclosing the tube. According to a one embodiment, the at least one tube gripper can be aligned with the at least one actuator. If there are a plurality of actuators and a plurality of tube grippers, two or more tube grippers may be aligned with a respective number of actuators. According to one embodiment, the tube gripper can lift and hold a tube with respect to a closure holder wherein the closure holder and/or actuator can cooperate with the tube gripper to remove a closure from the sample tube or reclose the tube with its original closure held by the closure holder. It can however also be possible to adapt the device such that the tube gripper can hold a sample tube without lifting it while the closure holder and/or the actuator are moved with respect to the tube gripper. Alternatively, the tube gripper and the closure holder and/or the actuator can move with respect to each other.
According to one embodiment, the closure gripper can comprise a gripping tool and a pre-tensioning member connected to the gripping tool, such as a spring, pre-tensioning the gripping tool with respect to the closure holder in one pivoting direction (closing direction) for exercising a pressure on the sides of a closure symmetrically arranged in between. The pressure can be released upon coupling the actuator to the passive closure gripper by a force applied by the actuator on the pre-tensioning member (opening direction). Thus the closure can be held hanging by the gripping tool without touching other surfaces or parts of the device until disposed or returned to its respective sample tube.
According to one embodiment, the gripping tool can comprise a plurality of jaws symmetrically arranged with respect to a central vertical axis of the closure holder. Each jaw can comprise a friction surface, such as, for example a plurality of protrusions, such as, for example, conical protrusions that are, for example, arranged in a two-dimensional array, the jaws cooperating with each other to grip and hold a closure.
This embodiment can be particularly advantageous for removing and holding closures of variable shape and material and also for reclosing sample tubes with the closures since the maximum gripping power with the minimum contact surface can be achieved. In this way, a closure can be held firmly without falling during holding or sliding through the jaws during decapping or recapping. Moreover, asymmetrical deformations of the closure can be prevented for smooth and efficient decapping and recapping. Also, only a minimum contact between the gripper and the outer sides of the closure takes place, thus minimizing the risk of cross-contamination from one closure to the next closure due to possible sample traces present on the inside and/or bottom surface of the closure. According to one embodiment, each jaw can pivot about a horizontal jaw axis by varying its angle relative to the central vertical axis of the closure holder. This can enable the jaws to adapt to different inclinations of the sides of the closure without losing gripping surface and power.
According to one embodiment, the closure holder can comprise a passive closure push element, independent from the gripping tool, comprising a resilient member, for example, a spring, for exercising a push force on the closure in a vertical direction when the pressure of the gripping tool is released. The push element may be advantageously mounted above the gripping tool, such as, for example, the jaws. In this way, upon inserting a closure in the space between the gripping tool, e.g., by lifting a closed sample tube towards the closure holder, the push element can be pushed upwards by the closure and the resilient member can be tensioned. The resilient force of the resilient member can be chosen such that it is weaker than the resilient force of the pre-tensioning member. Therefore as long as the closure remains tight held by the gripping tool during the holding period, the push element can be limited to exercise only a pressure on the top of the closure without additional effects. In the event that a closure is returned to a sample tube during reclosing, the effect of the push element can also be marginal, even though it may contribute to the closing. In the event that a closure needs to be disposed by releasing the pressure of the gripping tool, e.g., by opening the jaws upon coupling with the actuator, and allowing the closure to fall by gravity, it may occasionally happen that a closure remains stuck or that a closure gripper remains jammed. The push element can be advantageously designed to expel the closure by pushing it out from the closure holder. The push element may be however designed for exercising an additional effect, especially on certain types of closures such as rubber stoppers having a concave shape, i.e., a cavity, on the top of the closure. In this case, if the push element is shaped to fit at least into part in the cavity of the closure, asymmetrical deformation and/or tilting of the closure may be prevented when gripping the closure by the gripping tool. This can enable proper decapping and recapping of the sample tube.
According to one embodiment, the closure gripper can rotate about the central vertical axis of the closure holder upon coupling the actuator to the passive closure gripper. The actuator can comprise a closure-gripper drive for rotating the closure gripper. Rotation may be necessary for threaded screwable closures. Rotation may however be advantageous for other types of closures as well, not necessarily requiring screwing. According to a one embodiment, the closure gripper can be rotated thus rotating the closure with respect to the tube, while the tube gripper maintains the tube stationary. Alternatively, it is possible to rotate the tube while maintaining the closure stationary between the gripping tool.
According to one embodiment, the device can comprise a closure-holder drive for sequentially and/or repeatedly bringing the plurality of closure holders in coupling connection with one or more actuators and/or a tube conveyor for bringing a tube at a time in gripping alignment with a tube gripper.
According to one embodiment, the device can comprise a decapping station where a decapping actuator is aligned to a decapping tube gripper, a recapping station where a recapping actuator is aligned to a recapping tube gripper, wherein a closure holder and a tube can move from the decapping station where the decapping actuator and the decapping tube gripper cooperate with the passive closure gripper to remove a closure from the tube, to the recapping station wherein the recapping actuator and the recapping tube gripper cooperate with the same passive closure gripper holding the closure to reclose the same tube with the same closure. The decapping and recapping actuators may be structurally identical but have different dedicated functions, i.e., for decapping and recapping respectively. In particular, they can be coupled to and actuate the same passive closure gripper but may be more specifically adapted for either decapping or recapping, for example, by setting the closure-gripper drive to rotate a passive closure gripper clockwise or counterclockwise.
According to one embodiment, the decapping/recapping device can comprise a decapping station comprising a decapping tube gripper and a recapping station comprising a recapping tube gripper. A closure holder can move from the decapping station where the closure gripper cooperates with the decapping tube gripper to remove a closure from the tube, to the recapping station where the closure gripper cooperates with the recapping tube gripper to reclose the same tube with the same closure.
According to one embodiment, the plurality of individual closure holders can be arranged on a translatable linear array or a rotatable rotor-like array or a robotic arm-like transportation unit, with possible random access to any actuator and/or decapping and/or recapping and/or waste station. According to a one embodiment, the plurality of closure holders can be symmetrically arranged on a carousel-type rotor comprising a plate or branches rotatable about a central rotor axis. The closure-holder drive may comprise a motor driving the carousel in a controlled manner about its axis via e.g., a belt-pulley or gear-like mechanism or induction like mechanism. The rotor may comprise a position sensor for controlling and/or monitoring the angle of rotation such as to facilitate a proper alignment between actuator and closure holder at every rotation.
Sample tubes may be moved with respect to the device, particularly with respect to a decapping and/or recapping station. Sample tubes can be carried on tube carriers, which may be either single tube carrier, so called “Pucks”, or multi-tube carriers, so called “tube racks”, comprising a plurality of tube receptacles for receiving e.g., up to 5 tubes or more and typically can receive different types of tubes, i.e., of variable diameter and height. According to a one embodiment, the decapping/recapping device can comprise a tube conveyor that can move sample tubes on single tube carriers and/or tube racks. The tube conveyor may therefore comprise a transportation unit, such as a transportation band or guide rail driven by a motor and arranged such that a tube carrier can be moved stepwise for bringing a tube at a time in alignment with a decapping and/or recapping station. The transportation unit may however move tubes on special tube carriers customized according to the requirements of a decapping/recapping device and can be confined in the working area of the decapping/recapping device. In this case, a reformatting device for transferring sample tubes from pucks and/or tube racks to these special carriers and vice versa may be operatively coupled to the decapping/recapping device. The closure-holder drive and the tube conveyor can be synchronized to bring a tube and its closure to the same recapping station after the closure has been removed at a decapping station.
According to one embodiment, the decapping/recapping device can comprise a height determining detector cooperating with the tube gripper for determining the height at which a tube can be lifted when removing a closure from a tube or reclosing the tube with its closure. The height determining detector may be for example a code reader for reading a code placed on a tube or a tube carrier and identifying the type of tube or rack, e.g., a bar code reader or an RFID reader. The height determining detector may also be optical, comprising e.g., a camera-type detector or other light sensor to measure geometrical parameter of the sample tubes and/or closures, particularly the height and/or the diameter of the tube and/or the size and shape or color of the closure. The height determining detector may be set up to send a signal to the tube gripper either directly or via a control unit. In this way the variability of the sample tube type can be taken into consideration and each sample tube can be lifted according to its respective geometric parameters, enabling its closure to be gripped and removed or enabling the tube to be reclosed with its closure held by the closure holder.
According to a one embodiment, the tube gripper can comprise a first tube gripping tool and a second tube gripping tool. The first tube gripping tool can be biasable with respect to the second gripping tool and cooperating with the second tube gripping tool such as the first tube gripping tool can grip and lift a tube from a tube carrier before the second gripping tool grips and holds securely the tube with a force and a surface of contact which can be greater than the force and surface of contact of the first gripping tool respectively. This double gripping mechanism can enable gripping the side wall of a tube in the often narrow space between a tube carrier and a closure with a smaller gripper means and to lift it to a height wherein a larger and stronger gripping tool can grip a longer portion of the side wall for a more secure grip.
According to one embodiment, the decapping/recapping device can comprise an error detector comprising a sensor and a controller to determine whether a closure has been removed and/or a tube has been reclosed with its respective closure and/or to prevent that a tube is reclosed with a non-respective closure. The error detector may be the same, similar or share components with the height determining detector. In particular, the error detector may comprise an optical detector, e.g., a camera-type detector or other light sensor can measure geometrical parameters and/or the presence or absence of a closure on a respective sample tube and/or in a closure holder. In particular, the error detector may be set up to compare a closed sample tube before decapping and after recapping. In the event of any error in the decapping/recapping process, it may emit a warning or alert signal and/or to interrupt the decapping/recapping process and/or to instruct the device to dispose a closure which failed to reclose a sample tube before it is accidentally brought in contact with other closures or other sample tubes. Further, it may send instructions to the system to process sample tubes left open or tubes, which failed to be opened, differently from the rest of the tubes. Alternatively, it may send instructions to the decapping/recapping device to reclose with a new closure a tube, which was entered in the system already open or which failed to be reclosed with its original closure.
According to one embodiment the device can comprise a waste station comprising a waste compartment. A closure holder can move to the waste station to dispose a closure into a waste compartment. According to one embodiment, the waste station can comprise a waste actuator aligned to a waste compartment. The closure holder can move from a decapping station where a decapping actuator and a decapping tube gripper cooperate with the passive closure gripper to remove a closure from the tube, to the waste station wherein the waste actuator cooperates with the same passive closure gripper holding the closure to dispose the closure into the waste compartment. Alternatively or in addition, the closure holder may move from a recapping station where a recapping actuator and a recapping tube gripper cooperate with the passive closure gripper to reclose a tube with its respective closure, to the waste station. This may happen in the event that an error occurred when trying to reclose the tube and the closure remained in the closure holder. In order to free the closure holder and make it available for another closure from another tube and/or to prevent that a different tube is closed with a closure that does not belong to that tube, the closure can therefore be disposed at the waste station before the closure holder is returned to a decapping or recapping station.
According to one embodiment, the device can comprise at least one decapping station and at least one waste station. According to one embodiment, the device can comprise at least one decapping station and at least one recapping station. According to one embodiment, the device can comprise at least one decapping station, at least one recapping station and at least one waste station. According to one embodiment, a plurality of closure holders can move from one station to another station. According to one embodiment, the plurality of closure holders can move from one station to another station for to be in turn coupled to a respective actuator. It can be possible that a closure holder only passes by a station without being coupled to an actuator. This may be for example the case if the closure holder is moved from a decapping station to a recapping station via a waste station. As there is no intention to dispose of the closure because the closure will be used to reclose its respective tube at the recapping station, there will be no coupling between the actuator and the passive closure gripper at the waste station unless an error in the intended process was detected. It can also be possible that a plurality of closure holders can move together with a respective number of actuators from one station to another station.
In a system operating with single tube carriers, the decapping station and the recapping station can be located at a distance from each other, which can correspond to the distance between the center of a tube and the center of a second apart tube in a series of tubes whose carriers are adjacent to each other. The pipetting station can be located in the middle, i.e., in correspondence to a tube in between. In one embodiment, the number of closure holders can be three. In this way, a cycle may be defined wherein in a same fixed time frame three tubes may be processed and three different steps may be performed. In particular, a first tube may be opened while a volume of sample is being withdrawn from or a volume of liquid is being dispensed into a second tube previously opened while a third tube, from or into which a volume of liquid has been previously withdrawn or a volume of liquid has been previously dispensed is being reclosed with the same closure that in the same time frame has been transported by one of the closure holders from the decapping station to the recapping station. The cycle can then start over again.
In a system operating with tube racks, the decapping station and the recapping station can be located at a distance from each other, which can correspond to the distance between the center of a tube in the first receptacle of a first tube rack and the center of a first tube in the first receptacle of a second tube rack adjacent to the first tube rack. This can be advantageous if the distance between the centers of two tubes on the same rack is not the same as the distance between the center of the last tube and the center of the first tube respectively on adjacent racks. The pipetting station can be located approximately in the middle, i.e., between decapping station and recapping station in correspondence to one of the intermediate tube positions. In the case of tube racks comprising five receptacles for receiving a respective number of tubes, in one embodiment, the number of closure holders can be six. In this way, a cycle may be defined wherein three tubes may be processed and three different steps may be performed in a same fixed time frame. In particular, a tube on a rack, e.g., the first tube, may be opened while a volume of liquid is being pipetted from or into one of the tubes in a preceding rack previously opened while another tube, e.g., the first tube on the preceding rack, from which or into which a volume of sample has been previously pipetted, is being reclosed with the same closure that in the same time frame has been transported stepwise by one of the six closure holders from the decapping station to the recapping station.
According to one embodiment, closures can be moved from a decapping station to a recapping station following a path of travel which does not overlap with the path of travel of the sample tubes except at the decapping station and recapping station. Analogously, according to one embodiment, the pipetting unit can be moved following a path of travel, which does not overlap with the path of travel of opened sample tubes, except at the pipetting station. In this way, it can prevent samples in opened tubes from being contaminated by eventual droppings from the closures while being held by a closure holder or from the pipetting unit.
Alternatively or in addition, the device may comprise a plate or shield located underneath the path of travel of the closure holders to protect other parts of the device from eventual droppings from closures held by the closure holders. Also, when cross-contamination is of particular concern such as when samples are used for nucleic acid amplification, other or additional measures may be implemented such as separating parts of the device in different compartments or enclosing the device or parts of it in an aerosol free compartment such as a hood.
As each work cell may be designed for processing a certain number of samples or sample tubes per time unit, and this number may vary, the system may be advantageously set up such that the number of closure holders and/or the number of actuators and/or the number of tube grippers and/or the number of pipetting units and/or the number of analytical units is variable in correspondence to each work cell according to the throughput and workflow of each work cell.
Also, as each work cell may process only or either sample tubes on single carriers or on racks carrying a plurality of tubes, each decapping/recapping device may advantageously process sample tubes transported on either single tube carriers and/or racks carrying a plurality of sample tubes.
According to a one embodiment, the system can comprise a transportation unit for automatically transporting sample tubes from one work cell to another work cell. The transportation unit may also transport single carriers or tube racks or both. The transportation unit may comprise e.g., one or more transport lines arranged e.g., as transport bands or guide rails. In particular, the transportation unit may be connected to, e.g., be an extension of, the tube conveyor of various decapping/recapping devices. Bypass lines and/or junctions may also be present so that specific work-cells may be accessed in a random-access manner, by delivering the right sample to the right work-cell at the right time, according to need or priority and/or according to the type of tube or tube carrier, and not necessarily sequentially. The transportation unit may alternatively comprise a series of autonomous robotic carriers with random access to any work cell. Alternatively, sample tubes and/or tube carriers may be transported from one work cell to another work cell manually by the user.
According to one embodiment, the system can comprise a programmed controller for instructing the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or for instructing the system to move or dispose the sample tube, based e.g., on the measurement of at least one sample parameter by the analytical unit. The programmed controller may be self-instructing and/or user instructing. The programmed controller may be for example part of a computing unit embodied as one or more programmable control computers or control units running one or more computer-readable programs, which is able to receive data, in particular results from the analytical unit, to compare these results with expected values or value ranges, and react according to the outcome of said comparison. It may for example instruct the pipetting unit to dispense a volume of diluting buffer to a sample should a parameter measured by the analytical unit exceed a threshold value. Alternatively, it may flag a sample as not suitable for further analysis by an analytical work cell. The programmed controller may therefore avoid unnecessary workflow by sparing time and costs. The same or different programmed controller may in addition or in alternative comprise a user interface. For example, it may be programmed to give the user the opportunity to decide about the next step, e.g. by providing a number of options and asking to choose one.
The computing unit, in general, may comprise functional entities such as at least a memory for storing at least reference parameter ranges to be compared with the measured parameters and a microprocessor for carrying out the comparison. The computing unit may also perform several other tasks and/or be connected to another computing unit performing other tasks. Also several control units, each dedicated to a set of tasks may be integrated with or connected to the system, e.g., to control specific components. The functional entities may be directly integrated in one or more work cells or connected to them, e.g., by electrical connection. In other words, the computing unit may comprise a computer electrically connected to the system and/or one or more control units integrated with the system. The computing unit may in general receive information from the decapping/recapping device and in particular from the error detector and generate corresponding control signals for controlling the operations of the error detector and/or of the decapping/recapping device as explained above.
A method for processing sample tubes can comprise transporting a sample tube closed by a closure to a first work cell. The closure can be removed from the sample tube with a first decapping/recapping device in correspondence to the first work cell. At least one aliquot of sample can be withdrawn from the sample tube by at least one pipetting unit in correspondence to the first work cell for being processed by the first work cell and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter of the sample with at least one analytical unit in correspondence to the first work cell. The sample tube can be reclosed with a closure with the first decapping/recapping device. The sample tube closed by the closure is transported to a second work cell. The closure is removed from the sample tube with a second decapping/recapping device in correspondence to the second work cell. At least one aliquot of sample is withdrawn from the sample tube by at least one pipetting unit in correspondence to the first work cell for being processed by the first work cell and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter with at least one analytical unit in correspondence to the first work cell.
According to one embodiment, the method can comprise reclosing the sample tube with the same closure that was removed from the sample tube.
According to one embodiment, the method can comprise opening a sample tube by removing the closure from the sample tube at a decapping station, withdrawing a volume of sample from the open sample tube and/or dispensing a volume of liquid into the open sample tube with the pipetting unit at a pipetting station and reclosing the sample tube with the same closure at a recapping station.
According to one embodiment, the method can comprise determining whether a closure has been removed and/or a sample tube has been reclosed with its respective closure and preventing a tube from being reclosed with a non-respective closure by disposing the closure which failed to reclose its respective tube and/or instructing the system to reclose the tube with a new closure.
According to one embodiment, the method can comprise instructing the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or instructing the system to move or dispose the sample tube, based on the measurement of at least one sample parameter by the analytical unit.
According to one embodiment, the method can comprise moving a tube and its closure independently from each other but in a synchronized manner from a decapping station, where the closure is removed, to a recapping station, where the tube is reclosed with the same closure, and pipetting a volume of sample from the opened tube and/or dispensing a volume of liquid into the opened tube and/or determining at least one parameter of the sample in the time frame between decapping and recapping.
Referring initially to FIG. 1, FIG. 1 shows schematically one example of a system 900 for processing sample tubes. The system 900 can comprise a plurality of work cells 901-909. In particular, the system 900 can comprise a pre-analytical work cell 901, a post-analytical work-cell 909, a plurality of analytical work-cells 902-906 can process preferably sample tubes on single carriers and two analytical work-cells 907, 908 can process preferably sample tubes on tube racks. The system 900 can further comprise a transportation unit 920 that can transport sample tubes on both single carriers and tube racks from one work cell to another work cell according to the need. The system 900 can further comprise a decapping/recapping device 911-918 in correspondence to work cells 901-908 respectively for removing a closure from a sample tube when a sample needs to be withdrawn and/or a liquid needs to be dispensed and/or a sample parameter needs to be determined and for reclosing the sample tube before it is transported to another work cell 901-909. Sample tubes can therefore be transported closed from one work cell to another work cell. The system 900 can further comprise in correspondence to each of work cells 901-908 respectively a pipetting unit 921-928 for withdrawing a volume of sample from a sample tube to be processed by the work cell 901-908 and/or dispensing a volume of liquid into the sample tube. The system 900 can further comprise analytical units 931, 937 in correspondence to work cells 901 and 907 respectively for determining at least one sample parameter of a sample contained in a sample tube.
The system 900 can further comprise a computing unit 940 configured to receive information from the decapping/recapping devices 911-918, from the analytical units 931, 937 and from the error detector (not shown) and generate corresponding control signals for controlling the operations of the error detector, of the decapping/recapping devices 911-918, of pipetting units 921-928, of analytical units 931, 937, of the transportation unit 920.
FIG. 2a shows one exemplary embodiment wherein a pipetting unit 150 for withdrawing volumes of samples from sample tubes 12 and/or dispensing volumes of liquid into sample tubes 12, is arranged in correspondence to a decapping/recapping device 100 (more clearly illustrated in FIG. 2b), for removing closures 11 of variable type 11′, 11′′ from sample tubes 12 of variable type 12′, 12′′, and for reclosing the same tubes 12′, 12′′ with the same respective closures 11′, 11′′. The decapping/recapping device 100 can comprise six individual closure holders 20 arranged symmetrically on a rotatable carousel 61, having a respective number of arms 62, each arm adapted for receiving one closure holder 20. Each closure holder 20 can comprise a passive closure gripper 21 for holding a closure 11. The device 100 can further comprise three actuators 40 and in particular a decapping actuator 40′ for actuating the passive closure grippers 21 when removing a closure 11 from a tube 12, a recapping actuator 40′′ for reclosing the tube 12 with its respective closure 11, and a waste actuator 40′′′ for eventually releasing a closure 11 into a waste compartment (not shown). The device 100 can further comprise two tube grippers 50. In particular, it can comprise a fixed decapping station wherein a decapping tube gripper 50′ is aligned with the decapping actuator 40′ and cooperates with the decapping actuator 40′ for biasing a tube 12 and its closure 11 away from each other when removing the closure 11. It can further comprise a fixed recapping station wherein a recapping tube gripper 50′′ is aligned with the recapping actuator 40′′ and cooperates with the recapping actuator 40′′ for biasing the tube 12 and its closure 11 towards each other when reclosing the tube 12. The decapping actuator 40′ can be coupled to a passive closure gripper 21 of a closure holder 20 when a closure 11 is removed from a tube 12. The recapping actuator 40′′ is coupled to a passive closure gripper 21 of a closure holder 20 when a tube 12 is reclosed with its respective closure 11. The waste actuator 40′′′ can be coupled to a passive closure gripper 21 of a closure holder 20 when a closure is disposed. An actuator 40 is decoupled from a passive closure gripper 21 when the closure holder 20 is holding a closure 11.
The pipetting unit 150 can be synchronized with the decapping/recapping device 100 to withdraw a volume of sample from an opened sample tube or dispense a volume of liquid into the sample tube 12 in the time frame between the opening of a tube 12 and the reclosing of the tube 12 with the same closure 11.
FIGS. 3a to 3d show more in detail the structure of a closure holder 20 and the working mechanism of a passive closure gripper 21 according to one embodiment. In particular, FIG. 3a shows the closure holder 20 from outside. FIG. 3b shows the inside of the passive closure gripper 21 in its passive mode. FIG. 3c shows the inside of the passive closure gripper 21 when it is activated. FIG. 3d shows a bottom view of the closure holder 20 in its passive mode. The closure holder 20 can have a symmetrical construction comprising an upper coupling part 22 for coupling to an actuator 40 and a lower cylindrical part 23 comprising a cavity 36 for receiving a closure 11 (closure not shown). The passive closure gripper 21 can comprise three cantilever arms 28 pivotable about horizontal fulcrum elements 38 and symmetrically arranged with respect to a central vertical axis 37 of the closure holder 20. Each cantilever arm 28 can comprise a jaw 27 mounted at the lower end and a wheel 30 mounted at the upper end. A cantilever spring 29 can also be mounted on one side of each cantilever arm 28 for exercising a force on the cantilever arm 28 such as the lower end and therefore the jaw 27 can be pushed towards the outside of the lower part 23 of the closure holder 20 absence of other forces. The passive closure gripper 21 can further comprise a pre-tensioning member comprising a passive element 31 and a coil spring 32 and symmetrical arranged with respect to the axis 37. The passive element 31 can comprise a pin protruding out of the coupling part 22 of the closure holder 20 along axis 37 and a lower conical part providing a surface of contact with the coil spring 32 at the bottom and with the wheels 30 on the side. The force can be applied by the coil spring 32 to the passive element 31 and therefore the force applied by the passive element 31 to the three cantilever arms 28 can be greater than the sum of the forces applied by the three cantilever springs 29 to the three cantilever arms 28. Thus, the force of the coil spring 32 prevails pushing the passive element 31 upwards and the wheeled ends of the cantilever arms outwards, i.e., the jawed ends of the cantilever arms 28 are pushed inwards against the force of the cantilever springs 29, which tend to push them outwards (FIG. 3b). Each jaw 27 can comprise two surfaces facing the inside of the closure holder 20 and forming an angle of about 120°. The three jaws 27 thus can form a regular geometrical gripping surface (FIG. 3d) which can enable a more efficient grip and can prevent asymmetrical deformations of the closure 11. Further each jaw 27 can comprise a series of conical protrusions 35 which can act as friction surface for an even better grip, i.e., for preventing sliding or misplacement during decapping, recapping or holding of the closure 11, while reducing the points of contact. If a closure 11 (not shown in FIG. 3a-d) is located in between the jaws 27, the pressure applied symmetrically to the outside of the closure 11 can be such that the closure 11 can be held passively in place. In addition, each jaw 27 can pivot about a horizontal jaw axis 38′ and can be capable of varying its angle relative to the central vertical axis 37 of the closure holder. This can enable the jaws to adapt to different inclinations of the sides of a closure 11 without losing gripping surface and power.
Upon coupling with an actuator 40 (not shown in FIG. 3a-3d), a force can be externally applied to the passive element 31, which is greater than the force of the coil spring 32. The passive element 31 is therefore pushed downwards allowing the wheeled part of the cantilever arms 28 to disengage. The only force acting on the cantilever arms 28 is at this point that of the cantilever springs 29, which thus push the jawed ends of the cantilever arms 28 outwards (FIG. 3c), hence opening the jaws 27 and releasing the pressure from a closure 11 in between or allowing a new closure 11 to be inserted between the open jaws 27 before they are closed again. The lower part 23 of the closure holder 20 comprises an aperture 39 in correspondence to each cantilever arm 28, through which the jawed end of the cantilever arm 28 can extend when opening or when accommodating a closure 11 of larger diameter.
The closure holder 20 can further comprise a passive closure push element 33 comprising a resilient member, i.e., a second coil spring 34, for exercising a push force on the closure 11 in a vertical direction when the passive pressure of the jaws 27 is released. The push element 33 is shown in its relaxed position in FIG. 3b and in its tensioned position in FIG. 3c. The resilient force of the resilient member can be chosen such that it is weaker than the resilient force of the pre-tensioning member. In this way, upon inserting a closure 11 between the gripping tool, i.e., by lifting a closed sample tube 12 towards the closure holder 20, the push element 33 can be pushed upwards by the closure 11 and the second coil spring 34 can be tensioned. Therefore as long as the closure 11 remains tight between the jaws 27, during the holding period, the push element 33 is limited to exercise only a pressure on the top of the closure 11. In the event that the closure 11 is to be disposed, the push element 33 can provide a push impulse to the closure 11 contributing to expel it downwards out of the closure holder 20 when opening the jaws 27. The push element 33 can further fit with its bottom into a concave top of certain types of closure 11′, such as to prevent asymmetrical deformation and/or tilting of the closure 11′ when the jaws 27 apply a pressure on its sides, thus acting as a stabilizer of the closure 11′.
FIG. 4 shows an actuator 40, such as the decapping actuator 40′ and the recapping actuator 40′′ wherein some parts are removed for illustrative purposes. The actuator 40, 40′, 40′′ can comprise an active bolt 41 connected to a spindle motor 46 for exercising a pressure on the passive element 31 of a passive closure gripper 21 when the actuator 40, 40′, 40′′ and the passive closure gripper 21 are in a coupling connection, the force applied by the active bolt 41 can be greater than the force of the first coil spring 32. Thus, the active bolt 41 acting on the passive element 31 can indirectly open the jaws 27 every time that a closure 11 needs to be gripped or released. The actuator 40, 40′, 40′′ can further comprise a closure-gripper drive comprising a coupling disc 43 connected to a DC stepper motor 47 via drive belt 44 for rotating the closure holder 20 about its axis 37. The engagement between coupling disc 43 and coupling part 23 of the closure device 20 is further described below with reference to FIGS. 6a to 6c. 
In case of the waste actuator 40′′′ (shown in FIG. 2b), there is normally no need for rotating the passive closure gripper 21 but only to release the pressure applied to the closure 11 by opening the jaws 27. Therefore the waste actuator 40′′′ can comprise the active bolt 41 but not the closure-gripper drive for rotating the passive closure gripper 21.
FIGS. 5a and 5b refer to a closure-holder drive 60. The closure-holder drive 60 can comprise a carousel 61 comprising six arms 62, each carrying one of the six closure holders 20 as illustrated in FIGS. 2a and 2b. The carousel 61 can be mounted on a rotor 63 connected to a DC stepper motor 65 via a belt 66 for being rotated about an axis 67 in order to bring sequentially the closure holders 20 in coupling connection with any of the actuators 40. The closure-holder drive 60 can further comprise a position sensor 68 for assisting in determining the initial correct position and for controlling/monitoring the angle of rotation such as to facilitate a proper alignment between actuators 40 and closure holders 20 at every rotation.
FIG. 5b is a partially cut view of the carousel 61 of FIG. 5a showing how a closure holder 20 can be mounted on an arm 62 of the carousel 61. In particular, a disc 69 can be concentrically fixed around the coupling part 22 of the closure holder 20. The disc 69 can then be sandwiched into a chamber 64 of the arm 62 such as the lower part 23 of the closure holder 20 extends below the arm 62, the coupling part 22 of the closure holder 20 can extend in part above the arm 62 and the whole closure holder 20 comprising the disc 69 can rotate about the axis 37 with respect to the chamber 64.
FIG. 6 is a top view of the decapping/recapping device 100 and pipetting unit 150 of FIG. 2a wherein some parts removed for clarity. The actuators 40 can be fixed while the carousel 61 can rotate counterclockwise. Six closure holders 20 numbered respectively 1 to 6 can be arranged symmetrically at intervals of about 60° and at a distance from the center of the rotor 63, which can correspond to the distance of the active bolts 41 of the actuators 40 measured from the center of the rotor 63. The actuators 40 can also be so arranged with respect to each other so that coupling between a passive closure gripper 21 and any actuator 40 is possible upon rotating the rotor 63 of regular steps, in this case 60° or multiples of 60°. The device 100 can further comprise a tube conveyor, in this case a linear conveyor 90 to transport tube racks 91, each carrying up to 5 sample tubes 12. The distance between the decapping actuator 40′ and the recapping actuator 40′′ can correspond to the distance between the centers of six tubes 12, i.e., between two tubes 12 occupying the same respective position on two adjacent racks 91. In this way, two tubes 12 may be brought in alignment with two closure holders 20 and two actuators 40 at the same time. The conveyor 90 can be synchronized with the rotor 63 to advance the racks 91 stepwise such as a new tube 12 and a new closure holder 20 can be brought into alignment at the same time with the same actuator 40, in this case either the decapping actuator 40′ or the recapping actuator 40′′. The decapping tube gripper 50′ and the recapping tube gripper 50′′ can also be aligned with the decapping actuator 40′ and recapping actuator 40′′ respectively. In particular, the decapping tube gripper 50′ can be synchronized with the conveyor 90 to lift a tube 12 and with the rotor 63 to bring a free closure holder 20 in coupling connection with the decapping actuator 40′ such as to remove a closure 11 from that tube 12 at that position at that time. The recapping tube gripper 50′′ can be synchronized with the conveyor 90 to lift a tube 12 and with the rotor 63 to bring the same closure holder 20 holding the closure 11 previously removed from that same tune 12 in coupling connection with the recapping actuator 40′′ such as to reclose that tube 12 at that position at that time.
One possible workflow of the decapping/recapping device 100 according to this embodiment is summarized in the following example. At start, all six closure holders 20 can be free. The device 100 can be initialized, via position sensor 68 (not shown in FIG. 6), such as a closure holder 20, e.g. closure holder 20, 1 can be aligned with the decapping actuator 40′. The conveyor 90 can then be instructed to advance the racks 91 such as the first tube 12 on the first rack 91 is brought in alignment with the decapping actuator 40′ and therefore with the closure holder 20, 1 and the decapping tube gripper 50′. The decapping actuator 40′ can be coupled to the passive closure gripper 21 of closure holder 20,1 such as the active bolt 41 applies a force on passive element 31 thereby causing the jaws 27 to be opened. The decapping tube gripper 50′ can be instructed to lift the tube 12 until the closure 11 is at a height between the open jaws 27. In order to determine the height, account is taken of a measurement carried out by a sensor (not shown) during the advancement of the rack 91 determining the type of tube 12 and/or closure 11. The jaws 27 can then be closed by releasing the pressure by the active bolt 41. The decapping actuator 40′ can then be instructed to rotate the coupling disc 53 for rotating the passive closure gripper 21, while the decapping tube gripper 50′ can be instructed to pull the tube 12 downwards back on the rack, thereby cooperating with the decapping actuator 40′ to remove the closure 11 from the tube 12 via passive closure gripper 21 of closure holder 20, 1.
The rack 91 can then be advanced to another position, such that the next tube 12 is brought into alignment with the decapping actuator 40′ and the decapping tube gripper 50′. At the same time, the next closure holder 20, 6 can be brought into alignment with the decapping actuator 40′ by rotating the rotor 63 of 60° counterclockwise and the procedure can be repeated. The closure holder 20, 1 can thus move about 60° counterclockwise while holding passively the closure 11 removed from the first tube 12, the closure holder 20, 1 no longer being coupled to any actuator 40.
Performing this step five times, five tubes 12 can be opened and respective closures can be transported stepwise counterclockwise by about 60° at a time by respective passive closure holders 20, 1, 2, 3, 4, 5. When closure holder 20, 6 comes into alignment with decapping actuator 40′, closure holder 20, 1 holding the first closure 11, comes into alignment with recapping actuator 40′′. At the same time, while the 6th tube 12, i.e., the first tube on the second rack 91, comes in alignment with the decapping tube gripper 50′ and decapping actuator 40′, the first tube 12 on the first rack 91, which was first opened, comes into alignment with the recapping tube gripper 50′′ and recapping actuator 40′′, therefore with closure holder 20, 1 holding its respective closure 11, i.e. the same closure 11 removed from that same tube 12.
From this point on, the decapping station 70 and recapping station 80 can work in the same time frame, each performing its respective task of decapping and recapping. In particular, nearly the same steps of those carried out at the decapping station 70 occur at the recapping station 80 but in reverse order. Specifically, at the recapping station 80, the recapping actuator 40′′ can be instructed to rotate the coupling disc 43 for rotating the passive closure gripper 21 in the opposite direction, while the recapping tube gripper 50′ can be instructed to lift the tube 12 upwards towards the closure 11, using the same information on the type of tube already acquired, thereby cooperating with the decapping actuator 40′ to reclose the tube 12 with the same closure 11 via passive closure gripper 21 of closure holder 20,1. The angular position of the closure 11 with respect to the tube 12 can be different at the decapping station 70 and the recapping station 80 respectively. This is due to the fact that the tube 12 can be transported linearly from the decapping station 70 to the recapping station 80 without rotating on itself. On the other hand, the closure holder 20,1 can be transported with a rotational movement of the rotor 63 of about 300° counterclockwise from the decapping station 70 to the recapping station 80. There can be a difference of about −60° in the angular position of the closure 11 with respect to the tube 12 at the recapping station 80 compared to the decapping station 70. This difference may have an influence on the proper closing of a tube 12, especially if the closure 11 is of the screw type. In order to take account of this difference, the recapping actuator 40′′ can be instructed to rotate the coupling disc 43 for rotating the passive closure gripper 21 of an additional 60°. The active bolt 41 can then apply a force on passive element 31 thereby causing the jaws 27 to be opened and the recapping tube gripper 50′′ can be instructed to lower the tube 12 on the rack 91. The recapping actuator 40′′ can thus be decoupled from the closure holder 20, 1, which can again be free to return to the decapping station 70 for receiving a new closure and starting a new cycle.
The pipetting unit 150 can be synchronized with the decapping/recapping device 100 to withdraw a volume of sample and/or dispense a volume of liquid in the time frame between the opening of a tube 12 and the reclosing of the tube 12 with the same closure 11. The pipetting unit 150 can be temporarily lowered so that a needle (not shown in FIG. 6) can be dipped into a sample via the open end of a tube 12 when the tube 12 is at an intermediate position between the decapping station 70 and the recapping station 80 and during the time frame in which the decapping station 70 and/or the recapping station 80 are operating with other respective tubes and the rotor 63 is not rotating. Optionally a pipetting tube gripper (not shown) may be employed to lift the open tube 12 and facilitate the pipetting operation by shortening the distance of travel of the pipetting unit 150.
FIGS. 7a and 7b show in perspective from top and bottom respectively how an actuator 40, in particular a decapping actuator 40′ and recapping actuator 40′′ are being engaged with a passive closure gripper 21 (some parts removed for clarity). In particular, the coupling part 23 of the closure holder 20 can comprise two pins 26 on its upper surface located on opposite sides of the passive element 31 located at the center, the passive element 31 laying out of the line between the two pins 26, so that when the closure holder 20 is mounted on an arm 62 of the carousel 61 the passive element 31 and the two pins 26 can lay on a an imaginary circle having as radius the distance between the center of the passive element 31 and the center of the rotor 63. The coupling disc 43 can comprise on the bottom a groove 45 having a width and a depth large enough to allow the pins 26 and the passive element 31 to fit in. Additionally, the groove 45 can have a curvature corresponding to that of an imaginary circle having as radius the distance between the center of the active bolt 41 and the center of the rotor 63 such that the pins 26 and the passive element 31 can pass smoothly through when the carousel 61 is rotated. Engagement can be complete when the passive element 31 and the active bolt 41 are in alignment, the active bolt 41 being extendable and retractable through a hole in the center of the groove 45.
Each arm 62 can comprise an alignment element, such as a magnet 27, to attract a ferromagnetic element 28 located on one side of the coupling part 23 of each closure holder 20. In particular, each magnet 27 and each ferromagnetic element 28 can be located so that when the closure holder 20 is decoupled from an actuator 40, due to the magnetic force exercised by the magnet 27 on the ferromagnetic element 28, rotation of the closure element 20 about its axis 37 can be prevented and the same angular position of the closure holder 20 with respect to its respective arm 62 can be maintained during rotation of the rotor 63. Each magnet 27 and each ferromagnetic element 28 can be located so that the pins 26 of the closure holder 20 are aligned with groove 45 when a closure holder 20 is coupled to an actuator 40. When the closure holder 20 is coupled to a decapping actuator 40′ or recapping actuator 40′′ the coupling disc 43 can apply a rotational force to the closure holder 20 via groove 45 acting on the pins 26, which can be greater than the magnetic force, thereby causing rotation of the closure holder 20 about its axis 37.
FIG. 7c shows the actuator 40 and passive closure gripper 21 already engaged (some parts removed for clarity). The pins 26 and passive element 31 can be inside the grove 45, wherein the active bolt 41 can be aligned with the passive element 31. In addition, the active bolt 41 is shown while applying a force to the passive element 31 thereby establishing a first coupling connection between the actuator 40 and the passive closure gripper 21. Upon rotation of the coupling disc 43, a rotational force can also be applied to the closure holder 20, thereby establishing a second coupling connection. There is therefore a coupling connection only at the time when a force is transferred from the actuator 40 to the closure holder 20 or passive closure gripper 21. A closure holder 20 may be engaged, i.e., aligned with an actuator 40 without coupling taking place if not necessary. This is the case for example with the waste actuator 40′′. Moreover, engagement with the waste actuator 40′′′ can comprise only alignment between the active bolt 41 and passive element 31. Also, coupling can comprise only a transfer of force from the active bolt 41 to the passive element 31.
FIG. 8 shows a tube gripper 50 more in detail. The tube gripper 50 can comprise a first tube gripping tool 51 comprising two upper tube gripping jaws 51′, 51′′ mounted on two respective first tube gripping arms 55′ and 55′′, biasable with respect to each other. The tube gripper 50 can further comprise a second tube gripping tool 52 comprising two lower tube gripper jaws 52′ and 52′′ mounted on two respective second tube gripping arms 54′ and 54′′, biasable with respect to each other and in the same direction as the upper tube gripping jaws 51′, 51′′. In addition, first tube gripping arms 55′ and 55′′ can be mounted on second tube gripping arms 54′ and 54′′ respectively and can be biased with respect to second tube gripping arms 54′ and 54′′ via resilient means 53. Upper tube gripping jaws 51′, 51′′ and lower tube gripping jaws 52′ and 52′′ can each comprise a gripping surface for gripping a tube from opposite sides respectively, wherein the upper tube gripping jaws 51′, 51′′ can be longer than the lower tube gripping jaws 52′ and 52′′ and the gripping surface of the upper tube gripping jaws 51′, 51′′ can be smaller than the gripping surface of the lower tube gripping jaws 52′ and 52′′. The tube gripper 50 can further comprises a first DC stepper motor 56 connected via spindle drive 57 to second tube gripping arms 54′ and 54′′ for biasing the second gripping arms 54′ and 54′′ and therefore lower tube gripping jaws 52′ and 52′′ towards each other when gripping a tube 12 and away from each other when releasing a tube 12. Since first tube gripping arms 55′ and 55′′ are mounted on second tube gripping arms 54′ and 54′′, they can also be biased accordingly. The tube gripper 50 can further comprise a second DC stepper motor 58 for lifting and lowering second tube gripping arms 54′ and 54′′ and together first tube gripping arms 55′ and 55′′. Since upper tube gripping jaws 51′ and 51′′ are longer than lower tube gripping jaws 52′ and 52′′ and biasable with respect to each other via resilient means 53, the tube gripper 50 may be set up via motors 56 and 58 such that the upper tube gripping jaws 51′ and 51′′ can grip and lift a tube from a tube carrier before the lower tube gripping jaws 52′ and 52′′ can grip and hold securely a tube with a force and a surface of contact which are greater than the force and surface of contact of the upper tube gripping jaws 51′, 51′′ respectively. Analogously, the tube gripper 50 may be set up such that the lower tube gripping jaws 52′ and 52′′ can release the tube before the upper tube gripping jaws 51′ and 51′′ when lowering the tube back on the tube carrier.
FIG. 9a shows a perspective view of a decapping/recapping device 300 according to another embodiment. The difference with the decapping/recapping device 100 of FIG. 2b and FIG. 6 is that it can operate with single tube carriers 391 transported by conveyor 390. The decapping/recapping device 300 can comprise a fixed decapping actuator 340′ and a decapping tube gripper 350, 350′ aligned at a decapping station 370, a recapping actuator 340′′ and a recapping tube gripper 350, 350′′ aligned at a recapping station 380, a waste actuator 340′′ and a waste well 384 aligned with a waste compartment (not shown) at a waste station 385. Three closure holders 20 can be arranged symmetrically at intervals of about 120° on three respective arms 362 of a carousel 361, which can rotate counterclockwise via rotor 363. The decapping station 370, the recapping station 380 and the waste station 385 can also be so arranged with respect to each other that coupling between a passive closure gripper 21 and any actuator 340 is possible upon rotating the rotor 363 of regular steps of about 120° or multiples of about 120°. The device 300 can further comprise a tube conveyor, in this case a linear conveyor 390 to transport Pucks 391, each carrying a single tube 12. The distance between the decapping station 370 and the recapping station 380 can correspond to the distance between the centers of a first and third tube in a series of three tubes 12 carried by respective Pucks 391 adjacent to each other. In this way, two tubes 12 may be brought in alignment with two closure holders 20 and two actuators 340′, 340′′ at the same time. The workflow of this embodiment may be analogous to that described with reference to FIG. 6, except that a cycle can be completed every three tubes instead of six and the steps of rotation are of about 120° instead of about 60°.
FIG. 9b shows a pipetting unit 250 in correspondence to the decapping/recapping device 300 of FIG. 9a. The pipetting unit 250 can be synchronized with the decapping/recapping device 300 to withdraw a volume of sample and/or dispense a volume of liquid in the time frame between the opening of a tube 12 and the reclosing of the tube 12 with the same closure 11. The pipetting unit 250 can be temporarily lowered such as a needle 251 can be dipped into a sample via the open end of a tube 12 when the tube 12 is at an intermediate position between the decapping station 370 and the recapping station 380 and during the time frame in which the decapping station 370 and/or the recapping station 380 are operating with other respective tubes and the rotor 63 is not rotating. Optionally, a pipetting tube gripper (not shown) may be employed to lift the open tube 12 and facilitate the pipetting operation by shortening the distance of travel of the pipetting unit 250 and/or of the pipetting needle 251.
FIG. 9c shows the same decapping/recapping device 300 and pipetting unit 250 of FIG. 9b from another perspective. In particular the waste station 385 is more clearly shown, comprising a waste well 384 for guiding closures to be disposed into a waste compartment (not shown).
FIG. 9d shows a top view of the same decapping/recapping device 300 and pipetting unit 250 of FIGS. 9b and 9c for better appreciating the difference with FIG. 6.
FIG. 10 shows more schematically a top view of a decapping/recapping device 500 according to another embodiment, in operation with tube racks 91. The difference with the previous embodiments is that carousel 561 can have the shape of a ring and can accommodate a larger number of closure holders 20, in this case twenty. Further, only a decapping station 570 and recapping station 580 are shown, which can be arranged diametrically opposite with respect to the carousel 561. A cycle is in this case can complete every eleven tubes 12. It can be also noted that a pipetting tube gripper 550′′ can be arranged at the center of the device 500 to lift one of the opened tubes 12 when the tube 12 passes at that position and to facilitate the pipetting operation by shortening the distance of travel of the pipetting unit (not shown).
It should be clear that the above are just examples of possible embodiments and that variations are possible according to the particular need without departing from the. In particular, the system may be configured with a different number and combination of work cells, in correspondence to which a different number or type of decapping/recapping devices and/or pipetting units and/or analytical units can be configured. More in particular, the system may be configured with decapping/recapping devices different from the type elucidated herein, e.g., with a conventional type of decapping/recapping device as e.g., known in the art and/or combinations of the type of decapping/recapping device elucidated herein with conventional decapping/recapping devices. Also, the decapping/recapping device may operate with both single tube carriers and tube racks, wherein tube racks may carry a different number of tubes. Also, a different combination of the number of closure holders and actuators as well as a different arrangement may be conceived. Especially, a different coupling mechanism may be conceived. This can be achieved by having a decapping/recapping device for each work cell for removing a closure from a sample tube when and where needed and for reclosing the sample tube before it is transported to another work cell.
One advantage can be that the system can enable the adaptation of the throughput of decapping and recapping of sample tubes to the sample processing throughput and to the specific workflow of each work cell without depending by the throughput of a central or common decapping/recapping device. It can also be possible to adapt the decapping/recapping device to the type of sample tube carrier required by each work cell, which may differ from one another, e.g., single tube carrier or rack for carrying a plurality of sample tubes.
Another advantage can be that tubes may be transported closed by a closure within the system, that is from one work-cell to another and opened only when and where needed. In this way the risk of spilling samples out of the tubes, the risk of cross-contamination, evaporation and the bio-hazard risk can be minimized.
Other advantages can be obtained by using a decapping/recapping device comprising a plurality of individual passive closure holders each comprising a passive closure gripper, and at least one actuator for actuating said passive closure gripper when removing a closure or reclosing a tube, wherein one actuator is coupled to one passive closure gripper when a closure has to be removed from a tube or when a closure has to be released from the closure gripper and is decoupled from a passive closure gripper when the closure holder is holding a closure.
It is noted that terms like “preferably,” “commonly,” and “typically” are not utilized herein to limit the scope of the claimed embodiments or to imply that certain features are critical, essential, or even important to the structure or function of the claimed embodiments. Rather, these terms are merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present disclosure.
Having described the present disclosure in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the disclosure defined in the appended claims. More specifically, although some aspects of the present disclosure are identified herein as preferred or particularly advantageous, it is contemplated that the present disclosure is not necessarily limited to these preferred aspects of the disclosure.

## Claims

1. A system for processing sample tubes comprising biological samples, the system comprising:
at least two work cells for processing samples, wherein each of the at least two of the work cells comprises
a pipetting unit for withdrawing a volume of sample from a sample tube to be processed by at least one of the at least two work cells and/or dispensing a volume of liquid into the sample tube, and/or
an analytical unit for determining at least one sample parameter of the sample contained in the sample tube;

at least one transportation unit to transport sample tubes from one work cell to at least another work cell; and
a decapping/recapping device for each of the at least two work cells for removing a closure from the sample tube and for reclosing the sample tube before it is transported to another work cell;
wherein the decapping/recapping device comprises,
at least one closure holder, each comprising a closure gripper for gripping and holding the closure;
at least one tube gripper cooperating with the closure gripper for biasing the tube and its closure away from each other when removing the closure and for biasing the tube and the closure towards each other when reclosing the tube with the same original closure; and
a decapping station and a recapping station, wherein the closure holder moves from the decapping station where the closure gripper cooperates with a decapping tube gripper to remove a closure from the tube, to the recapping station where the closure gripper cooperates with a recapping tube gripper to reclose the same tube with the same closure.

2. The system according to claim 1, wherein the closure gripper is passive and the decapping/recapping device further comprises at least one actuator for actuating the passive closure gripper when removing the closure from the tube or reclosing the tube with its respective closure.

3. The system according to claim 2, wherein the actuator is coupled to the passive closure gripper of the closure holder when removing the closure from the sample tube or when reclosing the sample tube with its respective closure and is decoupled from the passive closure gripper when the closure holder is holding the closure.

4. The system according to claim 3,
wherein the closure holder and the sample tube move from the decapping station where a decapping actuator and the decapping tube gripper cooperate with the passive closure gripper to remove the closure from the sample tube, thereby opening the tube, to the recapping station where a recapping actuator and the recapping tube gripper cooperate with the same passive closure gripper to reclose the same tube with the same closure.

5. The system according to claim 1, wherein the decapping/recapping device comprises a tube conveyor to move sample tubes on single tube carriers and/or tube racks.

6. The system according to claim 1, further comprising,
a programmed controller for instructing the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or for instructing the system to move or dispose the sample tube, based on a measurement of at least one sample parameter by the analytical unit.