Patent ID: 12194626

DETAILED DESCRIPTION

Throughout this application, the terms “lower”, “middle”, “upper”, “top”, “bottom”, “inside”, “outside” are to be understood with reference to a vertically arranged storage container and storage column of the installation according to the invention.

FIGS.1,1A,2and2Ashow all the essential components of an installation1for handling and storing biological samples at very low temperatures, in particular under cryogenic conditions, according to the invention.

The biological samples are contained in containers. The biological samples can be of human, animal, plant or environmental origin.

In the illustrated example, the sample containers10implemented are commercially available storage tubes already in use (cryotubes, cryovials or sample storage tubes).

The installation1comprises storage columns2or racks. As shown inFIGS.3,3A,4and5, a storage column2extends along a longitudinal axis Z1 and has a honeycomb structure20. Each cell200can receive a sample container (tube)10translationally, transverse to the longitudinal axis Z1. The cells200can be round, hexagonal or square, triangular or any polynomial shape. The dimensions of the cells are adapted to the geometry of the sample containers (tubes)10being handled as well as to thermal contractions. The axis Y1 of the cells can be a horizontal axis or inclined to the vertical so that they can be arranged at an angle which facilitates holding of the sample tubes10in the rack2(FIG.5).

The installation1comprises at least one row, two in the illustrated example, of commercially available storage containers3.1to3.10, referred to as cryo-storage containers. These cryo-storage containers can be cryo-preservation containers, dewar-type containers, vacuum insulated tanks or cryogenic freezers. These containers are thermally insulated, their interior being able to be subjected to very low temperatures, in particular with liquid nitrogen being arranged as a cold source. Each container3.1to3.10can be of the double-walled type, in which a vacuum is created to guarantee thermal insulation with the outside.

Preferably, the containers3.1to3.10are fixed to the ground. As shown inFIGS.1and2, the storage containers can be of different sizes. They may have a full- or partial-opening, that is to say can be wide-necked or narrow-necked cryo-storage containers.

As can be seen best inFIG.1B, each container3comprises in its upper part a honeycomb grid30, each cell300of which can receive vertically a storage column2. Each container3is closed by a removable lid31.

The installation1according to the invention comprises an enclosure with a controlled environment (gaseous atmosphere, hygrometry, temperature), not shown, in which all the essential components are housed.

The installation1comprises a first gripping member4, adapted to grip a storage column2individually.

A multi-axis robot5(five to seven axes) is provided for handling the sample containers (tubes)10placed in the racks, as well as for moving the sample containers (tubes) or the storage boxes11containing them from or to the user interface station12. In the illustrated example, the multi-axis robot5is a 6-axis robot.

The end of the arm of the multi-axis robot is provided with a second gripping member6, adapted to grasp individually a container10or a storage box11with multiple compartments, each compartment being adapted to house a container10. Advantageously, the installation can be configured so as to adapt the gripping member6according to the element to be handled.

The installation1also comprises a first Cartesian robot7, arranged above the rows of storage containers3.1to3.10and comprising the six-axis robot5and a transfer tray100, preferably cooled by liquid nitrogen, on the same plate. The transfer tray100contains the storage box bottoms11required for placing or picking up the samples. The capacity of the transfer tray, that is to say the number of boxes11, can be adapted.

A ground frame70, formed by a machine-welded assembly or made of profiles, supports the first Cartesian robot7above the rows of storage containers3.1to3.10.

The first Cartesian robot7with three movement axes (X, Y, Z) allows the six-axis robot5and the transfer tray100to be moved longitudinally along the rows of storage containers3.1to3.10, but also laterally in order to access the various racks2, and lastly vertically in order to carry and move the first gripping member vertically in order to retrieve or replace the racks in the containers3.1to3.10. Thus, the longitudinal movement axis X of the Cartesian robot7is parallel to the alignment direction of the row(s) and the movement axis Z is vertical.

The horizontal movement axis can advantageously be constituted by two translation rails71,71arranged in the space between the two rows of storage containers3.1to3.10. The vertical movement axis can be advantageously constituted by two independent motorized translation axes72or can be of telescopic type, in order to reduce the vertical space requirement, in the case where the height of the ceiling in situ is limited.

The lateral movement axis73allows the first gripping member4to be laterally moved at least in line with any cell300of the grid30of any of the storage containers3.

All movement axes can be formed by translation axes with ball screw or belt drives, which can be supported by brushless or DC motors. The movement axes can also be formed by linear motors (“Direct-Drive Linear Stage” motors).

According to the invention, the installation is configured such that:i/ the first Cartesian robot7can move the six-axis robot5in the vicinity of any of the storage containers3.1to3.10;ii/ the first gripping member4retrieves vertically, at least partially, any of the racks2from one of the cells of the grid30of the storage container in a so-called pick-up position,iii/ the second gripping member6retrieves at least one selected container in the column pick-up position, and vice versa.

The installation1can include a clamping device8and retrieval device9, as shown inFIGS.6and6A, which is carried by the vertical movement axis72of the Cartesian robot7. The clamping device is used to hold, by its jaws80, a rack2when the latter is at least partially removed from a storage container3.FIGS.7A and7Bshow, respectively, the clamping device in a retrieval position at a distance and in the clamping position of the rack2gripped by the gripping member4.

FIGS.8A and8Bshow respectively the open and closed position of the jaws80around the rack2which is gripped by the first gripping member4.

The retrieval device9formed by retrieval fingers90actuated by cylinders, typically pneumatic cylinders, allows any tube10to be pushed from a cell200of a storage column2when the latter is at least partially retrieved from a storage container.

FIGS.9and9Ashow the retrieval, from its housing200in a rack2, of a sample tube10which is performed by pushing by a retrieval finger90.

A transfer tray100, carried by the longitudinal movement axis X of the first Cartesian robot7and arranged in the circular movement zone of the six-axis robot5, is intended to house a plurality of multi-compartment storage boxes11of sample tubes10.

At one end of the longitudinal movement axis X of the first Cartesian robot7there is arranged a preparation station12from which an operator can bring one or more containers10or one or more boxes11.

The longitudinal movement axis of the first Cartesian robot7can move the transfer tray100in the preparation station12.

The preparation station12can comprise a second Cartesian robot13with three axes of movement, adapted to bring the containers10or the boxes11into an airlock for the recovery of biological samples by an operator.

This second Cartesian robot13carries, on its vertical axis Z, a third gripping member14adapted to handle the storage boxes11individually and, on its lateral axis Y, a loading drawer15.

Lastly, a static transfer tray16that can hold storage boxes11is housed in the preparation station12.

As illustrated inFIG.3, each rack2advantageously comprises at least two wireless temperature measurement sensors, one of which21is arranged on an upper face of the rack and the other22is arranged on the lower face. The sensors21,22are connected by cables to an electronic printed circuit board (PCB) which can be individualized, i.e., one electronic printed circuit board23,24per sensor21,22respectively. The temperature measurement of the upper face of the rack is only carried out when the gripping member4, which is mounted on the vertical axis of the Cartesian robot7, is in contact with the desired rack (FIG.7). This can be implemented by touch points arranged on the gripper. The temperature reading makes it possible to authorize, or not, the exit of the rack according to the temperature measured on the rack. The temperature reading of the second temperature sensor22, or of a third temperature sensor25placed in the middle of the rack, makes it possible to provide a thermal map of the racks, especially when they are placed outside the containers3. The temperature readings thus make it possible to preserve the integrity of the samples by requiring that the rack be placed inside its container3when the temperature of the rack, in particular measured by the sensor21, approaches the maximum admissible temperature. On the other hand, the temperature readings make it possible to know the temperature gradients and the thermal contractions undergone by the rack22, moreover in a dynamic way. Indeed, the temperature readings can be acquired as long as the gripping device4is in contact with the rack2. This information makes it possible to guide the multi-axis robot5by integrating compensation coefficients related to the thermal contraction, in particular at the time of the phase of retrieval or placement of the samples in the racks.

Also as illustrated inFIG.3, the rack2can be equipped with complementary means and/or instead of the temperature sensors21,22,23: thus, strain gauges or RFID tags26,27,28can be fixed, which can integrate temperature sensors, preferably respectively in the lower, upper and middle part of the rack2.

An example of a gripping member4, carried by the vertical axis of the Cartesian robot7is shown inFIGS.10to12. It comprises a grip with one or more gripping arms40, in the form of jaws, advantageously three in number and arranged at 120° to each other.

In order to grip a storage column2, the arms40of the grip are spread apart from each other, the gripping lugs400then lock into the corresponding hollow part in the upper part of the column2(FIG.11).

In order to compensate for positioning errors and geometric variations of the parts along the X, Y and Z axes (manufacturing tolerances of the tubes10, boxes11and rack plates2), the gripping member4also comprises a force-free compliance module/body41, preferably of the type with integrated return springs, arranged above the arms of the grip. The implementation of the compliance module41is shown inFIG.12.

As shown inFIGS.10to12, the support of the gripping member42advantageously supports at least one support box43,44for touch points in which one or more touch points45are held which, when the rack2is gripped by the gripping member4, will come into contact with one and/or other of the two electronic printed circuit boards23,24of the rack2. These contacts, known as touch points, make it possible to ensure the reading of the temperatures respectively measured by the sensors21and22and possibly23or the sensors26,27,28integrated in the RFID labels.

FIG.13shows in detail the arrangement of the touch points45in a box43and their placement opposite a printed circuit board23for temperature readings.

The second gripping member6is shown in more detail inFIGS.14and15.

It comprises a grip with one or more gripping fingers60, advantageously three concentric gripping fingers arranged at 120° to each other.

To grip a sample tube10, the fingers60are brought together and locked around a tube10or inside the cap placed at the end of the tube.

In order to compensate for positioning errors and geometric variations of the parts along the X, Y and Z axes (manufacturing tolerance of the tubes10, boxes11), the gripping member6also comprises a force-free compliance module/body61, preferably of the type with integrated return springs, arranged above the grip.

The gripping member6furthermore comprises an anti-collision system62to avoid undesired contact/collision with another component as well as a laser or camera vision learning system63which makes it possible to learn the pick-up/set-down points of the different objects to be handled, by laser or image.

FIG.16shows an alternative design of the gripping member6in which the gripping fingers60are replaced by jaws64of the type used for the gripping member4of the Cartesian robot. With these jaws64, boxes containing a plurality of sample tubes can be gripped individually instead of the sample tubes retrieved individually with the fingers60.

The individual operating steps of the installation1according to the invention implemented by one or more control units and storage containers3.1to3.10will now be described, respectively for an operation of removing one or more sample containers (tubes)10individually from their storage to the outside of the installation enclosure and conversely for depositing one or more sample containers (tubes) individually from the outside of the enclosure into a storage container.

An operator makes a request to deposit one or more samples individually to the control unit of the installation1via an HMI (Human Machine Interface).

The control unit database checks that the specified sample tube location(s)10are available in one of the racks2of one of the containers3.1to3.10.

The operator then opens the loading drawer15, places the sample container(s)10in one or more transfer boxes11and closes the drawer15(FIGS.17and18).

If necessary, a barcode reader (not shown), placed under the storage zone of the transfer boxes11, scans a code on the sample tube10.

The second Cartesian robot13then transfers the transfer box(es)11placed on the loading drawer15to the static transfer tray16, preferably supplied with liquid nitrogen (FIGS.19and20).

The second Cartesian robot13performs the transfer of the transfer box(es)11placed in the static transfer tray16into the transfer tray100in the first Cartesian robot7(FIG.21).

The latter then performs a longitudinal movement X and lateral movement Y, which brings the transfer tray100out of the preparation station12(FIG.22) and then close to the selected storage container (cryo-storage container)3.2(FIG.23).

The gripping member4then removes the cap31from the selected cryo-storage container3.2(FIGS.23to25). For the removal of a partial-opening cap31, the Cartesian robot7performs a vertical downward movement (FIG.23), then a gripping of the cap31by the gripping member (FIG.24), a vertical upward movement, then a lateral movement, a vertical downward movement and finally a setting down of the cap (FIG.25).

If the cryo-storage container is a fully open container, only electrical control by the control unit of the installation or the Cartesian robot7is necessary.

The gripping member4is then positioned vertically on the target rack2by moving the Cartesian robot7along its vertical axis73(FIGS.26and27).

The gripping device4then grips the selected rack2(FIG.28) and the temperature of the rack2is measured at least by means of the temperature sensors21and22.

The rack2is then retrieved by vertical translation only of the Cartesian robot7(FIG.29). During this retrieval time, the temperatures are measured continuously.

Then, the clamping device8is moved (FIGS.30and31) and actuated in order to clamp the rack2in its retrieval position by the clamp80(FIG.32).

In this retrieved and clamped position of the rack2, the gripping member6at the end of the six-axis robot arm5retrieves the desired sample tube(s)10from the honeycomb structure20and then brings them individually into the transfer box11placed in the transfer tray100(FIGS.33and34). Conversely, the gripping member6can pick up other samples10already present in one or more of the transfer boxes11and place them in the rack2in the retrieved and clamped position.

During these operations, the six-axis robot5is guided by camera assistance and the control unit integrates compensation coefficients, associated with the temperature readings taken, in order to make the necessary movement corrections. Also during these operations, the transfer tray100is continuously supplied with liquid nitrogen to keep at very low temperature the transfer boxes11and the sample tubes10placed inside.

If necessary, at this stage a barcode reading is performed on the sample tubes in order to identify them.

Once the sample tubes10have been taken and placed in the transfer box(es)1and the necessary ones stored in the cells200of the rack2, the Cartesian robot7proceeds to put the rack2back into place in the cryo-storage container3.2by unclamping the grip80and then moving it vertically downwards by the movement axis73(FIGS.35to37). This operation of putting the rack2back in the cryo-storage container before clamping and/or after unclamping can also be carried out if the measurement of the temperatures of the rack2indicates that at least one of the temperatures is too high.

The cap31of the cryo-storage container3.2is then replaced using the Cartesian robot7(FIGS.38to41) or by closing the lid31of the cryo-storage container3.2by electrical control in the case of a full-opening container.

The control unit then controls the movement of the robot7to another cryo-storage container or in the preparation station12with a view to returning to the docking zone (FIGS.42and43).

The Cartesian robot13then returns the empty transfer boxes11or those containing retrieved sample tubes10that are in the transfer tray100to the loading drawer15(FIGS.44-46).

When the operator makes a request to retrieve the transfer boxes11, the Cartesian robot13comes to remove them from the loading drawer (FIGS.47and48).

Other variants and improvements can be envisaged without departing from the scope of the invention.

For example, if in the illustrated embodiments the Cartesian robot is carried by a ground frame, it can just as easily be suspended from the ceiling by a suitable gantry.

Another variant is illustrated inFIGS.49to51, where the Cartesian robot13is replaced by the six-axis robot5itself. In other words, according to this variant, the preparation station12no longer comprises its own Cartesian robot13, the functions of the latter being replaced by the six-axis robot5, which, once docked in its docking zone near the preparation station12, carries out the operations of taking sample tubes10and transferring the transfer boxes11placed in the static transfer tray16to the transfer tray100of this robot by means of the gripping member4that it carries, as explained with reference toFIGS.17to21, or vice versa.

FIGS.52and53show yet another example of a modification that can be made to the installation without departing from the scope of the invention. Here, the cap31of a partial-opening vessel (cryo-storage container) is modified. As shown inFIG.53, the gripping member4performs the removal and gripping of the partial-opening cap31by the Cartesian robot7, which performs a vertical downward movement. A vertical upward movement allows the cap31to be lifted.