HK1180039B - System for processing closed sample tubes - Google Patents

Description

System for processing closed sample tubes

Technical Field

The invention relates to the field of in vitro diagnostics and to a system for processing sample tubes, comprising a plurality of working units for processing samples. The invention also relates to a method of processing a sample tube comprising withdrawing a volume of sample from a tube processed by a working unit and/or dispensing a volume of liquid into a sample tube.

Background

Biological samples, such as blood samples, from different healthcare facilities are often present in different kinds of tubes with various caps in a laboratory. These are typically primary sample tubes, so called because they are used to collect samples, for example by venipuncture.

There are instruments that can process the primary sample tube without removing the cap, i.e., by accessing the sample contained in the primary tube by piercing the cap with, for example, a pipette needle. However, not all caps are suitable for this procedure, and not all types of instruments and/or analyses allow the use of this procedure. Certain types of instruments and/or assays require that the primary tube be opened before the sample is pretreated and/or analyzed. Therefore, such an instrument should have a cap remover that automatically removes the cap from the primary tube.

Automatic decapping of test tubes can be complicated by the variety of available primary tubes, which can vary in diameter, height, and particularly the variety of available caps. Some caps have threads for screwing onto a primary tube, for example. Another type of cover is a rubber stopper or cap that can be removed by a pulling motion. The caps may also differ in their composition. They may be made of rubber, plastic, etc. All or most of these types of primary tubes have been developed and are commercially available. These are typically modules integrated into a pre-analytical work cell, where one or more samples are taken from the sample tube and transported in a secondary tube to one or more analytical work cells for processing. The sample tube is then optionally reclosed with the same cap or a new cap.

An alternative approach is to open the primary sample tubes and process the original lids in a pre-analytical work cell, transfer the opened tubes to one or more analytical work cells for processing, and then reclose the tubes with new lids, typically in a post-analytical work cell.

One general problem is that sample processing throughput is limited by the decapping and/or recapping throughput of the pre-analytical work cell.

The present invention enables increased sample processing throughput in a system comprising a plurality of work cells.

According to the invention, this is achieved by having a decapping and/or recapping device for each working unit for removing the caps from the sample at the required time and place and for reclosing the sample tubes before they are transferred to another working unit.

An advantage of the present invention is to enable adaptation of the throughput of decapping and recapping of sample tubes to the sample processing throughput and the specific workflow per work cell, without relying on the throughput of a central or general decapping/recapping device. It is also possible to adapt the decapping/recapping device to the type of sample tube carrier required for each working unit, which may be different from each other, e.g. a single tube carrier or rack for carrying a plurality of sample tubes.

Another advantage of the invention is that the pipes can be transported closed by a cover within the system, from one working unit to another and only opened at the time and place of need. In this way, the risk of sample spillage outside the tube, the risk of cross-contamination, the risk of evaporation and the risk of biohazards can be minimised.

Further advantages are obtained by using a decapping/recapping device comprising a plurality of individual passive cap holders, each comprising a passive cap holder, and at least one actuator for actuating said passive cap holders upon removal of a cap or reclosing of a tube, wherein one actuator is connected to one passive cap holder when a cap has to be removed from a tube or when a cap has to be released from a cap holder, and one actuator is disengaged from the passive cap holder when the cap holder holds a cap.

This enables the various steps of opening, pipetting and reclosing to be carried out more independently of one another, without the need to use additional lids and without serious restrictions on the process steps. Furthermore, the reduction in cost and size of decapping/recapping devices can be achieved by even more suitably utilizing a plurality of such devices in the same system.

Disclosure of Invention

The present invention relates to a system for processing sample tubes. The system comprises two or more working units for processing the sample. The system further comprises correspondingly at least two working units, at least one pipetting unit for withdrawing a volume of sample from the sample tube processed by the working unit and/or dispensing a volume of liquid into the sample tube, and/or an analyzing unit for determining at least one sample parameter of the sample contained in the sample tube. The system further comprises a decapping/recapping device for each of the at least two working units for removing a cap from a sample tube and for reclosing the sample tube before it is sent to another working unit.

A "sample tube", also interchangeably referred to herein as a "tube", according to the present invention is a sample collection tube, also referred to as a "primary tube", for receiving a sample, such as a blood sample, from a patient and transferring the sample contained therein to an analytical laboratory for diagnostic purposes, or a "secondary tube", which may be used to receive a sample from the primary tube. The primary sample tube is typically made of glass or plastic, has a closed end and an open end closed by a cap, and may be made of different materials, take on different shapes and colors, typically related to the type of tube, i.e., the type of sample therein or the conditions to which the sample is subjected. For example, there are tubes containing anticoagulants or coagulation inducers, there are tubes containing gels that facilitate plasma separation, and so forth. Different types of primary tubes are often the result of customization by different primary tube manufacturers only. In most cases they reflect the type of sample and/or the analysis they are used for. In particular, there are different sizes of primary tubes, with different diameters and/or different heights, for receiving different numbers of samples. A single laboratory and often a single instrument is therefore required to be able to handle different types of primary tubes, possibly with different types of lids. The secondary tubes are typically made of plastic and may have a lesser degree of variation in size and type with respect to the primary tubes. In particular, the secondary tube may be smaller than the primary tube and designed to be closed with a cap of one or similar kind, for example of the screw type.

The term "cap" is used herein to indicate any type of cap, including screw-type caps and rubber stoppers, which can be opened and/or closed by pulling/pushing and/or screwing movements, respectively.

Within a larger instrument is a stand-alone device or module that assists a user in sample processing. By "sample processing" is meant testing, e.g., qualitative and/or quantitative assessment of a sample for diagnostic purposes, and/or sorting and/or preparing samples prior to testing, or storing and/or processing samples after testing. In particular, the working unit may be associated with an analytical and/or pre-analytical and/or post-analytical sample processing step. The work units may be interconnected and at least partially dependent on each other, e.g. each performing a dedicated task of the sample processing workflow, which may be a prerequisite before entering the next work unit. Alternatively, the working units may work independently of each other, e.g. each performing an independent task, e.g. different types of analysis on the same sample or on different samples.

An "analytical work cell" is a self-contained device or module within a larger instrument that assists a user in sample processing. Such as qualitative and/or quantitative assessment of samples for diagnostic purposes. It may include a processing and detection system whose workflow is optimized for certain types of analysis. Examples of such working units are clinical chemistry analyzers, coagulation chemistry analyzers, immunochemical analyzers, urine analyzers for detecting the results of, or monitoring the progress of, a chemical or biological reaction. The analytical work cell may comprise a cell which facilitates pipetting, dosing, mixing of samples and/or reagents. The working unit may comprise a reagent holding unit for holding a reagent to perform an assay. The reagents may be arranged, for example, in the form of containers or cassettes containing individual reagents or groups of reagents placed in appropriate containers or locations within a storage compartment or conveyor. It may comprise a reaction vessel or a cuvette supply unit. In particular, it may comprise one or more liquid handling units, such as pipetting units, to deliver samples and/or reagents to the reaction vessels. The pipetting unit may comprise a reusable washable needle, such as a steel needle, or a disposable pipetting tip. The working unit may further comprise one or more mixing units comprising e.g. a vibrator to vibrate a cuvette or a mixing blade comprising a liquid to mix the liquid in the cuvette or reagent container.

Within the larger instrument is a stand-alone device or module that assists the user in sorting and/or preparing the sample prior to processing by the analytical work cell. It may include, for example, one or more of the following: a reclassification unit that sorts samples according to the type of analysis and/or priority of the analysis, a centrifuge for centrifuging sample tubes, a portioning unit wherein a pipetting unit is used to portion samples from sample tubes, a heat treatment unit that subjects the samples to a certain temperature, a separation unit that separates sample components, and the like.

The "post-analytical work cell" is within the larger instrument a stand-alone device or module that assists the user in storing and/or processing the sample after being processed by the analytical work cell. It may, for example, comprise a reclassification unit to reclassify the sample tubes to, for example, different storage racks, and/or refrigerated compartments.

In general, the working unit may comprise a unit for loading and/or unloading and/or transporting and/or storing sample tubes or racks comprising sample tubes, a unit for loading and/or unloading and/or transporting and/or storing reaction vessels or cassettes, a unit for loading and/or unloading and/or transporting and/or storing and/or washing reaction vessels (e.g. cuvettes), a unit for loading and/or unloading and/or transporting and/or storing pipette tips or tip racks. It may comprise an identification unit comprising a sensor, such as a bar code or RFID reader. The instrument may also include one or more incubation units for maintaining the sample/reagent mixture at a temperature during the reaction, a washing station for washing the pipette tips or needles or reaction vessels, such as small vessels, stirring blades, and the like.

A "pipetting unit" according to the invention is a device that helps a user to automatically withdraw a volume of sample from a sample tube and/or dispense a volume of other liquid, such as a reagent or dilution buffer, into a sample tube or reaction vessel. The pipetting unit may comprise one or more reusable washable needles, such as steel needles, or use disposable pipetting tips. The suction unit may be mounted on a transfer head which can be moved in one or two travel directions in a plane, for example by means of a guide rail, and in a third travel direction perpendicular to the plane, for example by means of a spindle drive. By "corresponding to" is meant that the pipetting unit may be integrated into the working unit, i.e. built inside the working unit, or be a module of a system operatively connected to the working unit and/or the decapping/recapping device.

An "analysis unit" according to the present invention is a device for determining at least one sample parameter of a sample contained in a sample tube, e.g. a physical, chemical or biological parameter of the sample contained in the sample tube, typically without additional reagents. The analysis unit may for example be a sensor for determining a physical parameter of the sample, such as pH, temperature, color, turbidity, viscosity, or a quantity, such as volume, or level of the sample in the tube. It may for example comprise a light detector or probe, which is at least partially immersed in the sample. It may for example be suitable for determining a chemical or biological parameter, such as an analyte contained in a sample, by photometric measurements or other physical techniques using for example ion-selective electrodes or reagent-coated strips affected by a color change. By "corresponding to" is meant that the analysis unit may be integrated into the working unit, i.e. built inside the working unit, or be a module of a system operatively connected to the working unit and/or the decapping/recapping device.

The "decapping/recapping device" according to the present invention is a module within a separate device or system and assists the user in automatically opening and reclosing a sample tube when and where the sample needs to be taken out and/or liquid needs to be dispensed and/or sample parameters need to be determined, and for reclosing the sample tube before it is transferred to another working unit. In particular, the decapping/recapping device may be adapted to remove any type of cap from any type of sample tube, and may be adapted to reclose the sample tube with the same original cap or with a new cap. It may be integrated into, i.e. built inside, or operatively connected to the working unit.

According to one embodiment, the decapping/recapping device is adapted to reclose the sample tube with the same original closure and comprises at least one closure holder, each comprising a closure holder for holding and retaining a closure, e.g. when a volume of sample is taken and/or a volume of liquid is dispensed and/or sample parameters are determined. The device may further comprise at least one tube gripper cooperating with said gripper for biasing the tube and its closure away from each other when removing the closure and for biasing the tube and closure towards each other when reclosing the tube with the same original closure.

A "cap holder" is a device capable of holding a cap for a period of time during decapping, i.e., removing the cap from a sample tube, and processing the cap, or recapping, i.e., reclosing the same sample tube with the same corresponding cap. Each cap retainer comprises a cap gripper whose function is to securely hold the cap by frictional pressure applied to the outer surface of the cap, preventing the cap from moving and/or falling.

According to one embodiment, the cap gripper is passive and the decapping/recapping device further comprises at least one actuator for actuating said passive cap gripper when removing a cap from a tube or reclosing a tube with its respective cap.

According to one embodiment, the decapping/recapping device comprises a plurality of individual closure holders, each comprising a passive closure gripper for holding a closure.

According to one embodiment, the actuator is connected to the passive lid gripper of the lid holder when a lid has to be removed from a sample tube or a sample tube has to be reclosed with its respective lid, the actuator being disengaged from the passive lid gripper when the lid holder holds a lid.

"passive" means that there is a force or energy transfer between the passive cap holder and other components of the device, in particular the actuator, only when the cap is removed from the sample tube or the cap is processed or the sample tube is reclosed by its respective cap, and that there is no force or energy transfer between the passive cap holder and the actuator for a period of time during the decapping and processing or recapping, during which the force required to hold the cap is elastic and internal to the passive cap holder itself. Thus, the closure gripper needs to be connected to the actuator when decapping or recapping must occur and cannot do so when not connected to the actuator, which is passive in that respect.

An "actuator" is a device for actuation, i.e., transferring force or energy to the passive cap holder when removing a cap from a tube or reclosing a tube with its corresponding cap, the actuator being connected to the passive cap holder of the cap holder when a cap must be removed from a tube or when a tube must be disposed of or recapped by its corresponding cap, the actuator being disconnected from the passive cap holder when the cap holder holds a cap. According to one embodiment, the force is an axial force, transferred to the passive lid holder by applying a positive or negative pressure, for example by pushing or pulling a passive element of the passive lid holder. The force may also or alternatively be rotational, transferred to the passive lid holder by being connected to a rotational drive. However, the force may also be inductive, i.e. without direct contact, e.g. magnetic.

"connected to" or "coupled to" when referring to a relationship between an actuator and a passive lid holder means that the actuator engages with the passive lid holder, thereby enabling the transfer of force from the actuator to the passive lid holder. Engagement may occur through physical contact and/or alignment. By "disengaged" is meant that the actuator and the passive cap holder are no longer engaged, i.e., physically separated or misaligned from each other. Alternatively, the actuator and the passive cap holder may still be in physical contact or alignment, but the force transfer from the actuator to the passive cap holder is disabled, meaning that there is no force or energy transfer from the actuator to the passive cap holder anyway.

It is thus possible according to the invention to connect a plurality of closure holders with one or more actuators instead. According to one embodiment, one or more actuators are fixed within the device while a plurality of closure holders are movable relative to said fixed actuators, e.g. in turn connected to at least one actuator. Of course the reverse is also possible, wherein a plurality of closure holders are fixed, with respect to which one or more actuators are movable.

According to the present invention, the decapping/recapping device further comprises at least one tube gripper cooperating with the at least one closure holder and/or actuator for biasing the 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 one embodiment, at least one pipe gripper is aligned with 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 corresponding number of actuators. According to one embodiment, the tube gripper is adapted to lift and hold a tube relative to the closure holder, wherein the closure holder and/or actuator cooperates with the tube gripper to remove a closure from a sample tube or reclose the tube with its original closure held by the closure holder. It is however also possible to adapt the device such that the tube gripper can hold a sample tube without lifting it when the closure holder and/or the actuator is moved relative to the tube gripper. Alternatively, the tube holder and the closure holder and/or actuator may be movable relative to each other.

According to one embodiment the lid holder comprises a clamping means and a pretensioning member, e.g. a spring, connected to the clamping means, which in one rotational direction (closing direction) corresponds to the pretensioning clamping means of the lid holder for applying a pressure on the sides of the lid symmetrically arranged therein, wherein this pressure is releasable (opening direction) when the actuator is connected to the passive lid holder by a force exerted by the actuator on the pretensioning member. The caps are preferably suspended from contact with other surfaces or components of the device by the gripping tool until processed or returned to their respective sample tubes.

According to one embodiment, the gripping means comprise a plurality of jaws arranged symmetrically with respect to a central vertical axis of the cap holder, each jaw comprising a friction surface, e.g. a plurality of protrusions, e.g. conical protrusions, e.g. arranged in a two-dimensional array, the jaws cooperating with each other to grip and hold the cap.

This embodiment is particularly advantageous in removing and retaining covers of various shapes and materials and reclosing the sample tube with the cover, as maximum clamping dynamics can be achieved on a minimum contact surface. In this way the cap can be held firmly against falling down while being held or slid by the jaws during decapping or recapping. Furthermore, asymmetric deformation of the cap is prevented to ensure smoothness and efficiency of decapping and recapping. Furthermore, only minimal contact between the holder and the outside of the lid occurs, thus minimizing the risk of cross-contamination from one lid to the next, due to possible sample trajectories present on the inside and/or bottom surface of the lid. According to one embodiment, each jaw pivots about a horizontal jaw axis by varying its angle about a central vertical axis of the lid holder. This enables the jaws to accommodate different inclinations of the sides of the cover without loss of clamping surface and power.

According to one embodiment, the cap holder comprises a passive cap pushing element, independent of the gripping tool, comprising a resilient member, such as a spring, for exerting a pushing force on the cap in the vertical direction when the pressure of the gripping tool is released. The pushing element can advantageously be mounted above the gripping means, for example a claw. In this way, the resilient member is tensioned when the cap is inserted into the space between the gripping means, e.g. by the closed sample tube being lifted towards the cap holder, the pushing element being pushed upwards by the cap. The elastic force of the elastic member is selected such that it is weaker than the elastic force of the pre-tensioning member. The pushing element is therefore limited to exerting pressure only on the top of the lid without additional action during the holding as long as the lid remains held tight by the clamping tool. In the event of a lid being returned to the sample tube, the effect of the pushing element is marginal during reclosing, even though it may contribute to the closure. In the event that the lid needs to be handled by releasing the pressure of the gripping tool, for example by opening the jaws when connected to the actuator, and allowing the lid to fall by gravity, it may happen that the lid remains stuck or that the lid gripper remains stuck. The pushing element is thus advantageously designed to facilitate the ejection of the cap by pushing it out of the cap holder. The pushing element may however be designed for exerting an additional effect, in particular on certain types of caps, such as a rubber stopper on the top of the cap, which has a concave shape, i.e. a cavity. In this case, if the pushing element is shaped to fit at least partially in the cavity, asymmetric deformation and/or tilting of the lid can be prevented when the clamping tool clamps the lid. This allows for proper decapping and recapping of the sample tubes.

According to one embodiment, the lid holder is rotatable about a central vertical axis of the lid holder when the actuator is connected to the passive lid holder, the actuator comprising a lid holder driving device for rotating the lid holder. Rotation is necessary for a screwable cap. However, rotation is also advantageous for other types of caps, which do not necessarily need to be screwed. According to one embodiment, the closure gripper is rotated thereby rotating the closure relative to the tube while the tube gripper maintains the tube stationary. Alternatively, it is possible to rotate the tube while maintaining the cap stationary between the gripping tools.

According to one embodiment, the device comprises a cap holder drive for sequentially and/or repeatedly coupling a plurality of cap holders with one or more actuators, and/or a tube conveyor for clamping alignment of tubes with the tube holders each time.

According to one embodiment, the apparatus comprises a decapping station, wherein a decapping actuator is aligned to a decapping tube gripper, and a recapping station, wherein a recapping actuator is aligned to a recapping tube gripper, wherein a closure holder and a tube can be moved from the decapping station to a recapping station, wherein the decapping actuator and the decapping tube gripper cooperate with a passive closure gripper to remove a closure from a tube, and wherein the recapping actuator and the recapping tube gripper cooperate with the same passive closure gripper holding a closure to reclose the same tube with the same closure. The decapping and recapping actuators may be identical in structure, but have different dedicated functions, i.e. for decapping and recapping, respectively. In particular, they are suitable for connecting to and actuating the same passive cap holder, but more particularly may be suitable for decapping or recapping, for example by providing a cap holder drive means to rotate the passive cap holder clockwise or counterclockwise.

According to one embodiment, the decapping/recapping device comprises a decapping station comprising decapping tube holders, and a recapping station comprising recapping tube holders, wherein the closure holders are movable from the decapping station, where the closure holders cooperate with the decapping tube holders to remove closures from tubes, to a recapping station, where the closure holders cooperate with the recapping tube holders to reclose the same tubes with the same closures.

According to one embodiment, a plurality of individual closure holders are arranged in a transferable linear array or a rotatable rotor-like array or a robot arm-like transfer unit with possible random access to any actuator and/or decapping and/or recapping and/or waste station. According to one embodiment, the plurality of cap holders are symmetrically arranged on a rotating disc-shaped rotor, which comprises a plate or a branch, which is rotatable around a central rotor axis. The lid holder drive means may in this case comprise a motor which drives the rotary disk in a controlled manner about its axis by means of, for example, a belt pulley or a gear-like or inductive mechanism. The rotor may include a position sensor for controlling and/or monitoring the angle of rotation, for example to facilitate proper alignment between the actuator and the closure holder in each rotation.

The sample tube can be moved relative to the device, in particular relative to the decapping and/or recapping station. Sample tubes are preferably carried on a tube carrier, which may be a single tube carrier, a so-called "puck", or a multi-tube carrier, a so-called "tube rack", comprising a plurality of tube receptacles for receiving, for example, up to 5 tubes or more and generally adapted to receive different types of tubes, i.e. tubes of variable diameter and height. According to one embodiment, the decapping and/or recapping device comprises a tube conveyor adapted to move sample tubes on individual tube carriers and/or tube racks. The tube conveyor may thus comprise a conveying unit, such as a motor-driven conveyor belt or rail, which is arranged such that the tube carrier is moved stepwise for alignment with the decapping and/or recapping station at a time. The transfer unit may however be adapted to move tubes on a special tube carrier customized to the requirements of the decapping/recapping device and defined in the working area of the decapping/recapping device. In this case, the reconstitution device for transferring sample tubes from the discs and/or tube racks of these special carriers or vice versa is operatively connected to the decapping/recapping device. The closure holder drive and tube conveyor are preferably synchronized to bring the tube and its closure to the same recapping station after the closure has been removed at the decapping station.

According to one embodiment, the decapping and/or recapping device comprises a height determining detector cooperating with the tube gripper for determining a height to which the tube is to be raised when removing a cap from the tube or reclosing the tube with its cap. The height determining detector may for example be a code reader for reading a code placed on the tube or 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, including for example a camera-type detector or other light sensor, adapted to measure geometrical parameters of the sample tube and/or the cover, in particular the height and/or size of the tube and/or the shape or color of the cover. An example of such a camera type detector is disclosed for example in US 2010018330. The height determining detector may be arranged to send a signal to the tube gripper directly or via the control unit. In this way, variability in the type of sample tube is taken into account, each sample tube being raised according to its respective geometric parameters so that its lid can be gripped and removed or so that the tube can be reclosed with its lid held by the lid holder.

According to one embodiment, the pipe clamp comprises a first pipe clamping tool and a second pipe clamping tool, the first pipe clamping tool being biasable relative to and cooperating with said second pipe clamping tool, e.g. the first pipe clamping tool clamps and lifts a pipe from a pipe carrier before the second clamping tool firmly clamps and holds the pipe by a force and contact surface, which are larger than the force and contact surface of the first clamping tool, respectively. The dual gripping mechanism enables gripping of the sidewall of the tube with a smaller gripper device in the generally narrow space between the tube carrier and the cover, and raising it to a height where a larger and stronger gripping tool can grip the sidewall for more secure gripping.

According to one embodiment, the decapping and/or recapping device comprises an error detector comprising a sensor and a controller to determine whether a cap has been removed and/or a tube has been reclosed with its respective cap and/or to prevent a tube from being reclosed with or without its respective cap. The error detector may be the same, similar or common component as the height determination detector. In particular, the error detector may comprise a light detector, such as a camera type detector or other light sensor, adapted to measure geometrical parameters and/or the presence or absence of a cap on a respective sample tube and/or a cap in a cap holder. In particular, an error detector may be provided to compare closed sample tubes before decapping and after recapping. More specifically, in the event of any error in the decapping/recapping process, it may be configured to issue a warning or alarm signal and/or interrupt the decapping/recapping process and/or command the device to process the closure before it accidentally comes into contact with other closures or other sample tubes, which cannot reclose the sample tubes. Further, it may send a command to the system to process a sample tube that remains open or a tube that fails to open, as opposed to the remaining tubes. Alternatively, it may send a command to the decapping and/or recapping device to reclose the tube with a new cap, which entered in an already open system or which could not be reclosed with its original cap.

According to one embodiment, the apparatus comprises a waste station comprising a waste compartment, wherein the lid holder is movable to the waste station to place the lid into the waste compartment.

According to one embodiment, the waste station comprises a waste actuator aligned to the waste compartment, wherein the lid holder is movable from a decapping station, where the decapping actuator and decapping tube holder cooperate with the passive lid holder to remove a lid from a tube, to the waste station, where the waste actuator cooperates with the same lid holder holding a lid to place the lid into the waste compartment. Alternatively or additionally, the closure holder may be moved from the recapping station to the waste station where the recapping actuator and recapping tube holder cooperate with the passive closure holder to reclose the tube with its respective closure. This may occur in the event of an error in attempting to reclose the tube and cap retained in the cap holder. In order to release the cap holder and make it available for another cap of another tube and/or to prevent a different tube from being closed with a cap not belonging to that tube, the cap is therefore placed in a waste station before the cap holder is returned to the decapping or recapping station.

According to one embodiment, the apparatus comprises at least one decapping station and at least one waste station. According to one embodiment, the apparatus comprises at least one decapping station and at least one recapping station. According to one embodiment, the apparatus comprises at least one decapping station, at least one recapping station, and at least one waste station. According to certain embodiments, the plurality of lid holders are movable from station to station. According to some embodiments, the plurality of closure holders are movable from station to station for connection in turn to respective actuators. It is however possible that the closure holder only passes the station without being connected to the actuator. This may be an example of this: the closure holder is moved from the decapping station to the recapping station by the waste station. Because the caps are not intended to be processed, because for reclosing their respective tubes at the recapping station, there is no connection between the waste station actuator and the passive cap gripper unless an error in the intended process is detected. It is also possible that a plurality of closure holders may be moved together with a corresponding number of actuators from one station to another.

In a system optimized to operate with a single pipe rack, the decapping station and the recapping station are preferably positioned at a distance from each other, corresponding to the distance between the center of a pipe and the center of a second, separate pipe in a series of pipes, the carriers of a series of pipes being adjacent to each other, the pipetting station being located in the middle, i.e. corresponding to the pipe in between. In this case, the preferred number of cap holders is 3. Thus a cycle can be determined in which 3 tubes can be processed in the same fixed time frame and 3 different steps can be performed. In particular, the first tube may be opened when a volume of sample is pipetted from or into the previously opened second tube, while the third tube, from which a volume of liquid has been previously withdrawn or into which a volume of liquid has been previously dispensed, is reclosed with the same cap, within the same time frame that has been transferred by one of the cap holders from the decapping station to the recapping station. The cycle may then start again.

In a system optimized to operate with a pipe rack, the decapping station and the recapping station are preferably positioned at a distance from each other that corresponds to the distance between the center of a pipe in the first vessel of a first pipe rack and the center of a first pipe in the first vessel of a second pipe rack near the first pipe rack. It is 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 respective last tube and the center of the first tube on the adjacent rack. The pipetting station is also in this case approximately in the middle, i.e. between the decapping station and the recapping station, which corresponds to one of the intermediate tube positions. In the case of a tube rack comprising 5 containers for receiving a corresponding number of tubes, the preferred number of lid holders is 6. Thus a cycle can be determined where 3 tubes can be processed and 3 different steps can be performed within the same fixed time frame. In particular, a tube on a shelf, such as a first tube, may be opened when a volume of liquid is pipetted or pipetted from or into a previously opened tube in a preceding shelf, while another tube, such as a first tube on a preceding shelf, from or into which a volume of liquid has been previously pipetted or pipetted, is reclosed with the same closure, within the same time frame of the step-wise transfer from the decapping station to the recapping station that has been carried out by one of the 6 closure holders.

According to some embodiments, the caps are moved from the decapping station to the recapping station following a travel path that does not overlap with the travel path of the sample tubes except at the decapping station and the recapping station. Similarly, according to some embodiments, the pipetting unit follows a path of travel that does not overlap with the path of travel of the open sample tube except at the pipetting station. In this way, the sample in the opened tube is prevented from being contaminated by the end product discharged from the cap or by the pipetting unit while being held by the cap holder.

Alternatively or additionally, the device may comprise a plate or protective disc located below the travel path of the cap holder to protect other components of the device from the end product ejected by the cap held by the cap holder. Furthermore, when cross-contamination is a particular concern, for example when the sample is used for nucleic acid amplification, remaining or additional measures may be implemented, for example separating the components of the device in different compartments or closing the device or its components in a compartment without aerosol (e.g. a hood).

Since each work cell can be designed to handle a certain number of samples or sample tubes per time unit and this number can vary, the system can advantageously be arranged such that the number of lid holders and/or the number of actuators and/or the number of tube holders and/or the number of pipetting units and/or the number of analysis units is variable for each work cell depending on the throughput and workflow of each work cell.

Moreover, because each work cell may be designed to process only or preferably sample tubes on a single carrier or on a rack carrying multiple tubes, decapping/recapping devices may each be advantageously adapted to process sample tubes that are transported on a single tube carrier or on a rack carrying multiple tubes.

According to one embodiment of the invention, the system comprises a transport unit for automatically transporting sample tubes from one working unit to another. The transfer unit may also be adapted to transfer a single carrier or tube rack or both. The conveying unit may comprise one or more conveying lines, e.g. arranged in a straight line, e.g. as a conveyor belt or a guide rail. In particular, the transfer unit may be connected to the tube conveyors of various decapping/recapping devices, for example extensions thereof. Bypass lines and/or connections may also be present so that particular work cells may be accessed in a random access manner by delivering the appropriate sample to the appropriate work cell at the appropriate time, which need not be sequential as desired or prioritized and/or as a function of the type of tube or tube carrier. The transfer unit may alternatively comprise a series of autonomous robotic carriers that randomly access any of the work cells.

Alternatively, the sample tubes and/or the tube carriers can be transferred from one working unit to another working unit manually by a user.

According to one embodiment, the system comprises a programmed controller for commanding the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or for commanding the system to move or place the sample tube, e.g. based on a measurement of at least one sample parameter by the analysis unit. The programming controller may be self-and/or user-directed. The programmed controller may for example be a component of a computing unit, implemented as one or more programmable control computers or control units, running one or more computer-readable programs, which are able to receive data, in particular results from the analysis unit, compare these results with expected values or value ranges, and react on the basis of the results of said comparisons. If the parameter measured by the analysis unit exceeds a threshold value, it may for example command the pipetting unit to dispense a volume of dilution buffer to the sample. Alternatively, it may mark the sample by the analytical work cell as unsuitable for further analysis. The programming controller can thus avoid unnecessary workflows to save time and cost. The same or different programming controllers may additionally or alternatively include a user interface. For example, it may be programmed to give the user the opportunity to decide the next step, for example by providing a number of options and requesting a selection of one.

The calculation unit may typically comprise a functional entity, such as at least one memory, for storing at least reference parameter ranges, which are compared with the measured parameters and the microprocessor for performing 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 into or connected to the system, e.g. to control a specific component. The functional entities may be integrated directly into one or more work units or connected to them, e.g. by electrical connections. In other words, the computing unit may include a computer and/or one or more control units electrically connected to the system, which are integrated with the system. The calculation unit may typically receive information from the decapping/recapping device, in particular from the error detector, and generate corresponding control signals for controlling the operation of the error detector and/or the decapping/recapping device, as described above.

The invention also relates to a method for processing a sample tube, comprising the steps of:

a) transferring the sample tube closed by the cap to the first working unit,

b) removing caps from the sample tubes using a first decapping/recapping device corresponding to the first working unit,

c) taking at least one sample from the sample tube for processing by the first working unit using at least one pipetting unit corresponding to the first working unit, and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter of the sample using at least one analysis unit corresponding to the first working unit,

d) using said first decapping/recapping device to cap-reclose said sample tubes,

e) transferring the sample tube closed by the cap to a second working unit,

f) removing caps from the sample tubes using a second decapping/recapping device corresponding to the second working unit,

g) taking at least one sample from the sample tube for processing by the first working unit using at least one pipetting unit corresponding to the first working unit, and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter using at least one analysis unit corresponding to the first working unit.

According to one embodiment, the method comprises the step of reclosing the sample tube with the same lid removed from said tube.

According to one embodiment, the method comprises the steps of: the tube is opened by removing the cap from the tube at a decapping station, a pipetting unit is used to withdraw a volume of sample from the open tube or dispense a volume of liquid into the open tube at a pipetting station, and the tube is reclosed with the same cap at a recapping station.

According to one embodiment, the method comprises the steps of: determining whether a cap has been removed and/or a tube has been reclosed with its corresponding cap, and preventing a tube from being reclosed with either its respective cap by placing a cap that cannot reclose its respective tube, and/or commanding the system to reclose a tube with a new cap.

According to one embodiment, the method comprises the steps of: commanding the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or commanding the system to move or place the sample tube based on the measurement of the at least one sample parameter by the analysis unit.

According to one embodiment, the method comprises the steps of moving the tube and its cap independently of each other, but in a synchronized manner from a decapping station (where the cap is removed) to a recapping station (where the tube is reclosed with the same cap), aspirating a volume of sample from the open tube and/or dispensing a volume of liquid into the open tube and/or determining at least one parameter of the sample in a time frame between decapping and recapping.

Other and further objects, features and advantages of the present invention will become apparent from the following description and the accompanying drawings, which illustrate exemplary embodiments and serve to explain in greater detail the principles of the invention.

Drawings

Fig. 1 schematically shows a system for processing a sample tube comprising a plurality of working units.

Figure 2a shows a perspective view of a pipetting system including a decapping/recapping device according to one embodiment.

Fig. 2b is an enlarged view of the decapping/recapping device shown in fig. 2a, with some components removed for clarity.

Figure 3a shows one of the plurality of closure holders shown in figures 2a and 2 b.

Fig. 3b shows the cap holder of fig. 3a, where parts of the housing have been removed to make some internal components visible.

Fig. 3c provides a further perspective of the working principle of the closure holder of fig. 3a and 3 b.

Fig. 3d shows a bottom view of the lid holder of fig. 3 a.

Fig. 4 shows the actuator with some parts removed to show some internal components.

Figure 5a shows a rotor in the form of a rotating disc carrying a plurality of cap holders as shown in figures 2a and 2 b.

Fig. 5b shows a partial cross-sectional view of the rotating disk of fig. 5 a.

Fig. 6 is a top view of the system of fig. 2a, with some components removed for clarity.

Fig. 7a and 7b show how the actuator and the passive lid holder are engaged (some parts have been removed for clarity) in perspective view from the top and the bottom, respectively.

Figure 7c shows the actuator and passive lid holder of figures 7a and 7b engaged (some parts have been removed for clarity).

Figure 8 shows a tube gripper in more detail.

Fig. 9a shows a perspective view of a decapping/recapping device according to another embodiment.

Figure 9b shows a pipetting system including the decapping/recapping device of figure 9 a.

Figure 9c shows the same pipetting system of figure 9b from another perspective.

Fig. 9d shows a top view of the same pipetting system of fig. 9b and 9 c.

Fig. 10 shows a top view of a decapping/recapping device according to another embodiment.

Detailed Description

Fig. 10 schematically illustrates an example of a system 900 for processing sample tubes. The system 900 comprises a plurality of work units 901 and 909. In particular, system 900 comprises a pre-analysis work cell 901, a post-analysis work cell 909, a plurality of analysis work cells 902-906 adapted to preferably process sample tubes on a single carrier, and two analysis work cells 907, 908 adapted to preferably process sample tubes on a tube rack. The system 900 further comprises a transport unit 920 adapted to transport sample tubes on individual carriers and tube racks from one working unit to any other working unit as required. The system 900 further comprises a decapping/recapping system 911-. The sample tube is thus transported in a closed manner from one working unit to the other. The system 900 further comprises, in correspondence with each of the working units 901-908, a respective pipetting unit 921-928 for withdrawing a volume of sample from the sample tube for processing by the working unit 901-908 and/or for dispensing a volume of liquid into the sample tube. The system 900 further comprises analysis units 931, 937, which correspond to the working units 901 and 907, respectively, for determining at least one sample parameter of the sample contained in the sample tube.

The system 900 further comprises a calculation unit 940 configured to receive information from the decapping/recapping system 911-.

Fig. 2a shows an exemplary embodiment in which a pipetting unit 150 is used for taking a volume of sample from a sample tube 12 and/or dispensing a volume into a sample tube 12, which arrangement corresponds to a decapping/recapping device 100 (more clearly illustrated in fig. 2 b) for removing various types 11', 11 "of caps 11 from various types 12', 12" of sample tubes 12 and for reclosing the same tube 12', 12 "with the same respective cap 11', 11". The decapping/recapping device 100 comprises 6 individual closure holders 20 arranged symmetrically on a rotatable rotary disk 61, having a corresponding number of arms 62, each adapted to receive one closure holder 20. Each lid holder comprises a passive lid holder 21 for holding a lid 11. The apparatus 100 further comprises 3 actuators 40 for actuating said passive cap gripper 21 when removing the caps 11 from the tubes 12, and in particular a decapping actuator 40', a recapping actuator 40 "for reclosing the tubes 12 with their respective caps 11, and a waste actuator 40"' for finally releasing the caps 11 into a waste compartment (not shown). The device 100 further comprises two tube holders 50. In particular, it comprises a fixed decapping station in which a decapping tube gripper 50' is aligned with the decapping actuator 40' and cooperates with the decapping actuator 40' for biasing the tube 12 and its cap 11 away from each other when the cap 11 is removed. It further includes a stationary recapping station in which 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 toward each other when reclosing the tube 12. When the cap 11 has to be removed from the tube 12, the decapping actuator 40' is connected to the passive cap holder 21 of the cap holder 20. The recapping actuator 40 "is connected to the passive cap holder 21 of the cap holder 20 when the tube 12 has to be reclosed with its respective cap 11. The waste actuator 40 "' is connected to the passive lid holder 21 of the lid holder 20 when the lid has to be disposed of. The actuator 40 is disengaged from the passive lid holder 21 when the lid holder 20 is holding the lid 11.

The pipetting unit 150 is synchronized with the decapping/recapping device 100 that takes a volume of sample from an open sample tube or dispenses a volume of liquid into a sample tube 12, which is in the time frame between the opening of the tube 12 and the reclosing of the tube 12 with the same closure 11.

Fig. 3a to 3d show the structure of the passive lid holder 21 and the working mechanism of the lid holder 20 according to one embodiment in more detail. In particular, fig. 3a shows the lid holder 20 from the outside. Fig. 3b shows the interior of the passive lid holder 21 in its passive mode. Fig. 3c shows the interior of the passive lid holder 21 when it is activated. Fig. 3d shows a bottom view of the lid holder 20 in its passive mode. The cap holder 20 has a symmetrical configuration comprising an upper connecting part 22 for connection to the actuator 40, and a lower cylindrical part 23 comprising a cavity 36 for receiving the cap 11 (cap not shown). The passive lid holder 21 includes 3 cantilevered arms 28 that pivot about a horizontal fulcrum element 38 and are symmetrically disposed about a central vertical axis 37 of the lid holder 20. Each cantilever arm 28 comprises a jaw 27 mounted at a lower end and a wheel 30 mounted at an upper end. A cantilever spring 29 is also mounted on one side of each cantilever arm 28 for exerting a force on the cantilever arm 28 (e.g., lower end) so that the pawl 27 is urged toward the outside of the lower member 23 of the lid holder 20 when other forces are not present. The passive lid holder 21 further comprises a pretensioning member comprising a passive element 31 and a helical spring 32 and being arranged symmetrically with respect to an axis 37. The passive element 31 comprises a pin projecting outwards along the axis 37 from the connecting part 22 of the cover holder 20, and a lower conical part providing a contact surface with the helical spring 32 at the bottom and with the wheel 30 on the side. The force applied to the passive element 31 by the coil spring 32 and thus to the 3 suspension arms 28 by the passive element 31 is greater than the sum of the forces applied to the 3 suspension arms 28 by the 3 suspension arm springs 29. Thus, the force of the helical spring 32 mainly pushes the passive element 31 upwards and pushes the wheeled ends of the cantilever outwards, i.e. the claw ends of the cantilever 28 are pushed inwards against the force of the cantilever spring 29, which tends to push them outwards (fig. 3 b). Each claw 27 includes two surfaces which face the inside of the cap holder 20 and form an angle of 120 degrees. The 3 claws 27 thus form a regular geometric clamping surface (fig. 3 d) which enables a more effective clamping and prevents an asymmetrical deformation of the cover 11. Further each jaw 27 comprises a series of conical protrusions 35 which act as friction surfaces for even better gripping, i.e. for preventing slipping or dislocation during decapping, recapping or holding the cap 11 while reducing contact points. If the cover 11 (not shown in fig. 3a-3 d) is positioned between the claws 27, the symmetrically applied pressure to the outside of the cover 11 causes the cover 11 to be passively held in place. Furthermore, each jaw 27 is pivotable about a horizontal jaw axis 38' and is thus able to change its angle with respect to the central vertical axis 37 of the lid holder. This enables the jaws to accommodate different inclinations of the sides of the cover 11 without loss of gripping surface and power.

When connected to the actuator 40 (not shown in fig. 3a-3 d), a force is applied externally to the passive element 31, which is greater than the force of the helical spring 32. The passive element 31 is thus pushed downwards to allow disengagement of the wheeled part of the cantilever arm 28. The only force acting on the cantilever arms 28 is in this regard that of the cantilever springs 29, which thus push the claw ends of the cantilever arms 28 outwards (fig. 3 c), thus opening the claws 27 and intermediately releasing the pressure from the lid 11 or allowing a new lid 11 to be inserted between the open claws 27 before they are closed again. The lower part 23 of the lid holder 20 comprises a hole 39, which corresponds to each cantilever arm 28, through which the claw end of the cantilever arm 28 can extend when opening or when accommodating a lid 11 of large diameter.

The lid holder 20 further comprises a passive lid pushing element 33 comprising an elastic member, i.e. a second helical spring 34, for exerting a pushing force on the lid 11 in the vertical direction when the passive pressure of the claws 27 is released. The pushing element 33 is shown in its relaxed position in fig. 3b and in its tensioned position in fig. 3c for illustrative purposes. The elastic force of the elastic member is selected such that it is weaker than the elastic force of the pre-tensioning member. In this way, when the cap 11 is inserted between the clamping tools, i.e. by lifting the closed sample tube 12 towards the cap holder 20, the pushing element 33 is pushed upwards by the cap 11 and the second helical spring 34 is tensioned. The pushing element 33 is therefore limited to exerting pressure only on the top of the lid 11 during the holding as long as the lid 11 is held tight between the claws 27. In the event that the cap 11 has to be handled, the pushing element 33 provides a pushing thrust for the cap 11 to help push it out of the cap holder 20 when the jaws 27 are opened. The pushing element 33 is further designed to be adapted to enter with its bottom the concave top of some types of lids 11', for example to prevent asymmetrical deformation and/or tilting of the lid 11' when the claws 27 apply pressure on its sides, thus acting as a stabilizer of the lid 11 '.

Fig. 4 shows an actuator 40, such as a decapping actuator 40' and a recapping actuator 40", with some components cut away for illustrative purposes. The actuator 40, 40', 40 "comprises an active bolt 41 connected to a spindle motor 46 for applying a pressure on the passive element 31 of the passive cap holder 21 when the actuator 40, 40', 40" and the passive cap holder 21 are in a coupled connection, the force applied by the active bolt 41 being greater than the force of the first helical spring 32. Thus, the active bolt 41 acting on the passive element 31 has the function of opening the jaws 27 indirectly each time the lid 11 needs to be clamped or released. The actuator 40, 40', 40 "further comprises a lid holder driving means comprising a connection disc 43 connected by a drive belt 44 to a DC stepper motor 47 for rotating the lid holder 20 about its axis 37. The engagement between the connection disc 43 of the closure device 20 and the connection part 23 is further elucidated below with respect to fig. 6a to 6 c.

In the case of a scrap actuator 40' ' ' (shown in FIG. 2 b), it is generally not necessary to rotate the passive lid gripper 21, but rather the pressure applied to the lid 11 is released merely by opening the jaws 27. The waste actuator 40 "' thus comprises the active bolt 41 but no lid holder drive means for rotating the passive lid holder 21.

Fig. 5a and 5b relate to a lid holder drive 60. The lid holder drive 60 comprises a rotary disc 61 comprising 6 arms 62 each adapted to carry one of the 6 lid holders 20 as shown in fig. 2a and 2 b. The rotary disc 61 is mounted by a belt 66 on a rotor 63 connected to a DC stepper motor 65 for rotation about an axis 67 to sequentially couple the closure holder 20 with any actuator 40. The closure holder drive 60 further includes a position sensor 68 that assists in determining the initial correct position and for controlling/monitoring the angle of rotation, thereby facilitating correct alignment between the actuator 40 and the closure holder 20 at each rotation.

Fig. 5b is a partial cross-sectional view of the rotary disk 61 of fig. 5a showing the lid holder 20 mounted on the arm 62 of the rotary disk 61. In particular, the disc 69 is fixed concentrically around the connecting part 22 of the lid holder 20. The disc 69 is then clipped into the chamber 64 of the arm 62, for example the lower part 23 of the lid holder 20 extends below the arm 62, the connecting part 22 of the lid holder 20 extends partially above the arm 62, and its lid holder 20 including the disc 69 is rotatable about the axis 37 about the chamber 64.

Fig. 6 is a top view of the decapping/recapping device 100 and the pipetting unit 150 of fig. 2a, with some components removed for clarity. When the rotary disk 61 is rotatable counterclockwise, the actuator 40 is fixed. The 6 cap holders 20, respectively numbered 1 to 6, are symmetrically arranged at intervals of 60 degrees and at a distance from the center of the rotor 63, which corresponds to the distance of the driving bolt 41 of the actuator 40, measured from the center of the rotor 63. The actuators 40 are thus also arranged relative to each other such that a connection between the passive lid holder 21 and any actuator 40 is possible at regular step rotations of the rotor 63. In this case 60 degrees or a multiple of 60 degrees. The apparatus 100 further comprises tube conveyors, in this case linear conveyors 90 adapted to convey tube racks 91, each carrying up to 5 sample tubes 12. The distance between the decapping actuator 40' and the recapping actuator 40 "corresponds to the distance between the centers of 6 tubes 12, i.e. occupies the same respective position on two adjacent racks 91 between two tubes 12. In this way, two tubes 12 may be simultaneously aligned with two cap holders 20 and two actuators 40. The conveyor 90 is synchronized with the rotor 63 to advance the rack 91 stepwise, for example by simultaneously aligning a new tube 12 and a new closure holder 20 with the same actuator 40, in this case a decapping actuator 40' or a recapping actuator 40 ". The decapping tube gripper 50 'and the recapping tube gripper 50 "are also aligned with the decapping actuator 40' and the recapping actuator 40", respectively. In particular, the decapping tube gripper 50 'is synchronized with the conveyor 90 to raise the tube 12 and with the rotor 63 to release the closure holder 20 in coupled connection with the decapping actuator 40', e.g., at which point the closure 11 is removed from the tube 12 at that time. Recapping tube gripper 50 "is synchronized with conveyor 90 to raise the tube 12 and with rotor 63 to hold the same closure holder 20 with the closure 11 previously removed from the same tube 12 in coupled connection with the decapping actuator 40" to reclose the tube 12 at that point in time.

One possible workflow of decapping/recapping according to this embodiment is outlined in the following example.

At the beginning, all 6 closure holders 20 are free. The device 100 is initialized and aligned with the decapping actuator 40' by a position sensor 68 (not shown in fig. 6), such as the closure holder 20, e.g., closure holder 20, 1. The conveyor 90 is then commanded to advance the rack 91, e.g. the first tube 12 on the first rack 91 is aligned with the decapping actuator 40', and thus with the closure holders 20,1 and the decapping tube holder 50'. The decapping actuator 40' is connected to the passive cap holder 21 of the cap holder 20,1, e.g. the active bolt 41, exerting a force on the passive element 31, thereby causing the jaws 27 to be opened. The decapping tube gripper 50' is commanded to raise the tube 12 until the closure 11 is at the height between the open detents 27. To determine the height, the measurements performed by the sensors (not shown) during the advancement of the carriage 91 are considered to determine the type of tube 12 and/or cap 11. The jaws 27 are then closed by releasing the pressure from the active bolt 41. The decapping actuator 40' is then commanded to rotate the coupling disc 53 for rotating the passive lid gripper 21, while the decapping tube gripper 50' is commanded to pull the tube 12 back down on the shelf, thus cooperating with the decapping actuator 40' to remove the lid 11 from the tube 12 by the passive lid gripper 21 of the lid holder 20, 1.

The carriage 91 is then advanced in another position, such as with the next tube 12 aligned with the decapping actuator 40 'and decapping tube holder 50'. At the same time, the next closure holder 20,6 is aligned with the decapping actuator 40' by rotating the rotor 63 counterclockwise by 60 degrees, and the procedure is repeated. The cap holder 20,1 has also moved 60 degrees counter clockwise while passively holding the cap 11 removed from the first tube 12, the cap holder 20,1 is no longer connected to any actuator 40.

This step is performed five times, 5 tubes 12 being opened, the respective caps having been transferred by the respective passive cap holders 20,1,2,3,4,5 one step by step counterclockwise by 60 degrees. When the closure holder 20,6 comes into alignment with the decapping actuator 40', the closure holder 20,1 holds the first closure 11 in alignment with the recapping actuator 40 ". Meanwhile, when the 6 th tube 12, i.e., the first tube on the second rack 91, is aligned with the decapping tube gripper 50 'and the decapping actuator 40', the first tube 12 on the first rack 91 (which is first opened) enters into alignment with the recapping tube gripper 50 "and the recapping actuator 40", and thus with the closure holder 20,1 holding its respective closure 11, i.e., the same closure 11 removed from the same tube 12.

From this point on, the decapping station 70 and the recapping station 80 will operate in the same time frame, each performing its respective decapping and recapping tasks. In particular, almost the same steps performed at the decapping station 70 occur at the recapping station 80 but in the reverse order. In particular, at the recapping station 80, the recapping actuator 40 "is commanded to rotate the connecting disc 43 for rotating the passive closure gripper 21 in the opposite direction, while the recapping tube gripper 50 'is commanded to lift the tube 12 upwards towards the closure 11, using the same information about the type of tube that has been obtained, thus cooperating with the decapping actuator 40' to reseal the tube 12 with the same closure 11 by means of the passive closure gripper 21 of the closure holder 20, 1. It should be noted that the angular position of the caps 11 relative to the tubes 12 is different at the decapping station 70 and the recapping station 80, respectively. This is due to the fact that the tubes 12 have been linearly transferred from the decapping station 70 to the recapping station 80 without themselves rotating. On the other hand, the closure holder 20,1 has been transferred from the decapping station 70 to the recapping station 80 by a 300-degree rotational movement of the rotor 63 in the counterclockwise direction. There is a-60 degree difference in the angular position of the caps 11 relative to the tubes 12 at the recapping station 80 as compared to the decapping station 70. This difference may have an effect on the correct closing of the tube 12, in particular if the cover 11 is of the screw type. To account for this difference, the recapping actuator 40 "is commanded to rotate the interface disc 43 for an additional 60 degrees of rotation of the passive lid gripper 21. The active bolt 41 then exerts a force on the passive element 31, thereby causing the jaws 27 to open and the recapping tube gripper 50 "is commanded to lower the tube 12 on the rack 91. The recapping actuator 40 "is thus disengaged from the closure holder 20,1, which is again free to return to the decapping station 70 for receiving a new closure and starting a new cycle.

The pipetting unit 150 and 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 the tube 12 and the reclosing of the tube 12 with the same cap 11. In particular, the pipetting unit 150 is temporarily lowered, such as with a needle 251 (shown in FIG. 6) being dipped into the sample through the open end of the tube 12, while the tube 12 is in an intermediate position between the decapping station 70 and the recapping station 80, and during a time frame in which the decapping station 70 and/or the recapping station 80 are operated with other respective tubes and the rotor 63 is not rotated. Alternatively, a pipette holder (not shown) may be employed to raise the open tube 12 and facilitate the pipetting operation by shortening the travel distance of the pipetting unit 150.

Figures 7a and 7b show in perspective view from the top and bottom respectively how the actuator 40, in particular the decapping actuator 40' and the recapping actuator 40 "engage with the passive cap holder 21 (some parts have been removed for clarity).

In particular, the connection part 23 of the closure holder 20 comprises, on its upper surface, two pins 26, the upper surface being located on opposite sides of the passive element 31, the passive element 31 being located in the center, the passive element 31 being placed on a line between the two pins 26, so that when the closure holder 20 is mounted on the arm 62 of the rotary disk 61, the passive element 31 and the two pins 26 are placed on an imaginary circle having, as a radius, the distance between the center of the passive element 31 and the center of the rotor 63. The connecting disc 43 comprises a slot 45 on the bottom, having a width and depth large enough to allow the depth of the pin 26 and the passive element 31 to fit in. In addition, the slot 45 has a curvature corresponding to that of an imaginary circle having a distance between the center of the driving bolt 41 and the center of the rotor 63 as a radius, for example, the pin 26 and the passive element 31 can smoothly pass when the rotating disk 61 is rotated. When the passive element 31 and the active bolt 41 are aligned, the engagement is complete and the active bolt 41 is deployable and retractable through the hole in the center of the slot 45.

Each arm 62 comprises an alignment means, in this case a magnet 27, which attracts a ferromagnetic element 28 located on one side of the connecting part 23 of each lid holder 20. In particular, each magnet 27 and each ferromagnetic element 28 are positioned so that when the closure holder 20 is disengaged from the actuator 40, the rotation of the closure element 20 about its axis 37 is prevented due to the magnetic force exerted by the magnet 27 on the ferromagnetic element 28, the same angular position of the closure holder 20 with respect to its respective arm 62 being maintained during the rotation of the rotor 63. In particular, each magnet 27 and each ferromagnetic element 28 are positioned so that the pins 26 of the closure holder 20 are aligned with the slots 45 when the closure holder 20 must be connected to the actuator 40. When closure holder 20 is connected to decapping actuator 40' or recapping actuator 40", coupling disc 43 applies a rotational force to closure holder 20 through slot 45 acting on pin 26 that is greater than the magnetic force, thus causing rotation of closure holder 20 about its axis 37.

Fig. 7c shows the actuator 40 and passive cap holder 21 engaged (some parts have been removed for clarity). In particular, it shows the pin 26 and the passive element 31 within the slot 45, with the active bolt 41 aligned with the passive element 31. Furthermore, the active bolt 41 is shown when a force is applied to the passive element 31, thereby establishing a first coupling connection between the actuator 40 and the passive lid holder 21. When the coupling disc 43a rotates, a rotational force is also applied to the cap holder 20, thereby establishing the second coupling connection. There is thus a coupling connection only when force is transferred from the actuator 40 to the lid holder 20 or the passive lid holder 21. The closure holder 20 may be engaged, i.e., aligned with the actuator 40, without connection occurring when not needed. Such as with the waste actuator 40 ". Furthermore, the engagement with the waste actuator 40 "' only includes alignment between the active bolt 41 and the passive element 31. Furthermore, the connection only involves the transmission of forces from the active bolt 41 to the passive element 31.

Figure 8 shows the tube holder 50 in more detail. The pipe gripper 50 comprises a first pipe gripping tool 51 comprising two upper pipe gripping jaws 51', 51", which are mounted on two respective first pipe gripping arms 55' and 55", which are mutually biasable. The pipe gripper 50 further comprises a second pipe gripping tool 52 comprising two lower pipe gripping jaws 52' and 52 "mounted on two respective second pipe gripping arms 54' and 54", which are biasable towards each other and in the same direction as the upper pipe gripping jaws 51', 51 ". Furthermore, the first tube gripping arms 55' and 55 "are mounted on the second tube gripping arms 54' and 54", respectively, and are biasable relative to the second tube gripping arms 54' and 54 "by the resilient means 53. The upper tube gripping jaw 51', 51 "and the lower tube gripping jaw 52' and 52" each include a gripping surface for gripping the tube from opposite sides, respectively, wherein the upper tube gripping jaw 51', 51 "is longer than the lower tube gripping jaw 52' and 52" and the gripping surface of the upper tube gripping jaw 51', 51 "is smaller than the gripping surface of the lower tube gripping jaw 52' and 52". The tube gripper 50 further comprises a first DC stepper motor 56 connected to the second tube gripping arms 54' and 54 "via a spindle drive 57 for biasing the second gripping arms 54' and 54" so that the lower tube gripping fingers 52' and 52 "are towards each other when gripping the tube 12 and away from each other when releasing the tube 12. Because the first tube gripping arms 55 'and 55 "are mounted on the second tube gripping arms 54' and 54", they will also be biased accordingly. The tube gripper 50 further includes a second DC stepper motor 58 for raising and lowering the second tube gripping arms 54 'and 54 "and the first tube gripping arms 55' and 55" together. Because the upper tube gripping fingers 51' and 51 "are longer than the lower tube gripping fingers 52' and 52" and are mutually biasable by the resilient means 53, the tube gripper 50 may be set by the motors 56 and 58 so that the upper tube gripping fingers 51' and 51 "may grip and lift a tube from the tube carrier before the lower tube gripping fingers 52' and 52" may grip and securely hold the tube by a force and contact surface that is greater than the force and contact surface of the upper tube gripping fingers 51', 51", respectively. Similarly, when lowering a tube back on the tube carrier, the tube gripper 50 may be set before the upper tube gripping claws 51 'and 51 "so that the lower tube gripping claws 52' and 52" can release the tube.

Fig. 9a shows a perspective view of a decapping/recapping device 300 according to another embodiment. Which differs from the decapping/recapping device 100 of fig. 2b and 6 in that it is designed to operate preferably with single-tube carriers 391 transported by a conveyor 390. In particular, the decapping/recapping device 300 includes a fixed decapping actuator 340' and decapping tube holders 350, 350' aligned at the decapping station 370, a recapping actuator 340 "and recapping tube holders 350, 350" aligned at the recapping station 380, a waste actuator 340' ", and a waste well 384 aligned with a waste compartment (not shown) at the waste station 385. The 3 lid holders 20 are symmetrically arranged 120 degrees apart on 3 respective arms 362 of the rotary disk 361, which are rotatable counterclockwise by the rotor 363. The decapping station 370, the recapping station 380 and the waste station 385 are also arranged relative to each other such that a connection between the passive cap holder 21 and any actuator 340 is possible at regular step lengths where the rotor 363 rotates 120 degrees or multiples of 120 degrees. The apparatus 300 further comprises tube conveyors, in this case linear conveyors 390 adapted to convey pucks 391, each carrying a single tube 12. The distance between the decapping station 370 and the recapping station 380 corresponds to the distance between the centers of the first and third tubes of the series of 3 tubes 12 carried by the respective discs 391 adjacent to each other. In this way, two tubes 12 can be simultaneously aligned with two cap holders 20 and two actuators 340', 340 ". The workflow of this embodiment may be similar to that described with respect to fig. 6, except that the cycle is completed every 3 tubes instead of 6, and the rotation step is 120 degrees instead of 60 degrees.

Fig. 9b shows a pipetting unit 250, which corresponds to the decapping/recapping device 300 of fig. 9 a. The pipetting unit 250 is 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 the tube 12 and the reclosing of the tube 12 with the same cap 11.

In particular, the pipetting unit 250 is temporarily lowered, e.g., the needle 251 is dipped into the sample through the open end of the tube 12, while the tube 12 is in an intermediate position between the decapping station 370 and the recapping station 380, and during a time frame in which the decapping station 370 and/or the recapping station 380 are operated with other respective tubes and the rotor 63 is not rotated. Alternatively, a pipette holder (not shown) may be employed to raise the open tube 12 and facilitate the pipetting operation by shortening the travel distance of the pipetting unit 250 and/or the pipette needle 251.

Fig. 9c shows the same decapping/recapping device 300 and pipetting unit 250 of fig. 9b in another perspective view. In particular, waste station 385 is shown more clearly and includes a waste well 384 for directing placement of lids into a waste compartment (not shown).

Fig. 9d shows a top view of the same decapping/recapping device 300 and pipetting unit 250 of fig. 9b and 9c for better droplet performance than the difference of fig. 6.

Fig. 10 more schematically shows a top view of a decapping/recapping device 500 according to another embodiment, operating with a tube rack 91. The difference from the previous embodiment is that the rotating disc 561 has the shape of a ring and accommodates a larger number, in this case 20, of lid holders 20. Further, only a decapping station 570 and a recapping station 580 are shown, which are arranged diametrically opposite with respect to the rotating disc 561. In this case, the cycle is completed every 11 tubes 12. It is also noted that the pipette holder 550' ″ is disposed in the center of the device 500 to raise an open tube 12 as the tube 12 passes by in this position and facilitates the pipetting operation by shortening the travel distance of the pipetting unit (not shown).

It should be clear that the above are just examples of possible embodiments, variations are possible according to particular needs without departing from the scope of the invention. In particular, the system of the invention may be configured with different numbers and combinations of working units, corresponding to different numbers or types of decapping/recapping devices and/or pipetting units and/or analysis units that may be configured. More specifically, the system may be configured with a decapping/recapping device of a type different from that described herein, for example, in a traditional type of decapping/recapping device, as known in the art, and/or in combination with a traditional decapping/recapping device of a type described herein. Furthermore, the decapping/recapping device may be designed to operate with a single tube carrier and tube rack, where the tube rack may be adapted to carry a different number of tubes. Furthermore, different combinations and different arrangements of a plurality of cap holders and actuators may be envisaged. In particular, different connection mechanisms may be envisaged.

Claims (15)

1. A system (900) for processing sample tubes (12) comprising biological samples, the system (900) comprising two or more working units (901-:

a pipetting unit (921-928) for withdrawing a volume of sample from the sample tube for processing by the working unit and/or dispensing a volume of liquid into the sample tube,

an analysis unit (931, 937) for determining at least one sample parameter of a sample contained in the sample tube,

characterized in that the system (900) further comprises for each of the at least two working units (901-.

2. The system of claim 1, wherein the decapping/recapping device comprises:

at least one cap holder, each of which comprises a cap gripper for gripping and holding a cap,

at least one tube gripper cooperating with the cap gripper for biasing the tube and its cap away from each other when removing the cap and for biasing the tube and cap towards each other when reclosing the tube with the same original cap.

3. The system of claim 2, wherein the decapping/recapping device comprises a decapping station and a recapping station, wherein the closure holder is movable from the decapping station to the recapping station at which the closure gripper cooperates with the decapping tube gripper to remove a closure from a tube, and at which the closure gripper cooperates with the recapping tube gripper to reclose the same tube with the same closure.

4. A system according to claim 2 or 3, wherein the cap gripper is passive and the decapping/recapping device further comprises at least one actuator for actuating the passive cap gripper when removing a cap from a tube or reclosing a tube with its respective cap.

5. System according to claim 4, wherein the actuator is connected to the passive lid gripper of the lid holder when a lid has to be removed from a sample tube or when a sample tube has to be reclosed with its respective lid, the actuator being disengaged from the passive lid gripper when the lid holder holds the lid.

6. The system of claim 5, comprising a decapping station, wherein the closure holder and sample tube are movable from the decapping station to a recapping station, wherein the decapping actuator and the decapping tube gripper cooperate with the passive closure gripper to remove a closure from a sample tube, thereby opening a tube, and wherein the recapping actuator and the recapping tube gripper cooperate with the same passive closure gripper to reclose the same tube with the same closure.

7. The system of any one of the preceding claims, wherein the decapping/recapping device comprises a tube conveyor adapted to move sample tubes on individual tube carriers and/or tube racks.

8. A system according to any preceding claim, comprising a reconstitution device operatively connected to the decapping/recapping device for transferring sample tubes from a single tube carrier to a tube rack, or vice versa.

9. A system according to any one of the preceding claims, characterised in that it includes an error detector to determine whether a cap has been removed and/or a tube has been reclosed with its respective cap and/or to prevent a tube from being reclosed with or without its respective cap.

10. System according to any of the preceding claims, characterized in that the number of closure holders and/or the number of actuators and/or the number of tube holders and/or the number of suction units and/or the number of analysis units is variable for each work unit in dependence of the throughput and workflow of each work unit.

11. System according to any of the preceding claims, characterized in that it comprises at least one transport unit for transporting sample tubes from one working unit to at least another working unit.

12. The system according to any of the preceding claims, comprising a programmed controller for commanding the pipetting unit to perform one or more pipetting operations before the tube is reclosed and/or for commanding the system to move or place the sample tube based on the measurement of the at least one sample parameter by the analysis unit.

13. A method for processing a sample tube, the method comprising the steps of:

a) transferring the sample tube closed by the cap to the first working unit,

b) removing caps from the sample tubes using a first decapping/recapping device corresponding to the first working unit,

c) taking at least one sample from the sample tube for processing by the first working unit using at least one pipetting unit corresponding to the first working unit, and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter using at least one analysis unit corresponding to the first working unit,

d) using said first decapping/recapping device to cap-reclose said sample tubes,

e) transferring the sample tube closed by the cap to a second working unit,

f) removing caps from the sample tubes using a second decapping/recapping device corresponding to the second working unit,

g) taking at least one sample from the sample tube for processing by the first working unit using at least one pipetting unit corresponding to the first working unit, and/or dispensing a volume of liquid into the sample tube and/or determining at least one sample parameter of the sample using at least one analysis unit corresponding to the first working unit.

14. The method of claim 13, comprising the step of reclosing the sample tube with the same cap removed from the tube.

15. Method according to claim 14, characterized in that it comprises the following steps: determining whether a cap has been removed and/or a tube has been reclosed with its corresponding cap, and preventing a tube from being reclosed with either its respective cap by placing a cap that cannot reclose its respective tube, and/or commanding the system to reclose a tube with a new cap.