Abstract:
A device including a pre-analytical module provided with at least one tube stirrer for homogenizing blood and preventing clot formation and disposed on a line for single-tube transfer between an area for storing analyzable tubes, and at least one unitary operating whole blood analyzer and automatic tube-loading/unloading device arranged between the tube stirrer and the single-tube transfer line. The device is suitable for blood analyzers.

Description:
The invention relates to a device for supplying tubes of blood to whole blood analysers. 
     BACKGROUND OF THE INVENTION 
     I. Field of the Invention 
     Whole blood analysers are analysers which carry out analyses on tubes of blood containing all the elements of the blood, in contrast to analysers which work on blood plasma or serum. 
     II. Description of Related Art 
     In contrast to the analyses carried out on blood plasma or serum the blood which is to be analysed by a whole blood analyser has to be carefully mixed a very short time before the analysis. This agitation phase is absolutely necessary in order to homogenise the blood so as to re-suspend the cells which naturally settle out when the tube is motionless, and it has to be carried out in accordance with the recommendations of the standardisation committees. 
     This agitation phase is treated differently depending on the type of analyser used and its degree of automation. In the simplest analysers there are no agitation means in the apparatus and the agitation then has to be carried out manually by the operator prior to the analysis. 
     In more sophisticated analysers, and particularly in haematology equipment, the tubes are installed before analysis in agitators made up of wheels or racks. 
     In agitators provided with wheels the tubes of blood are placed in indentations arranged around the periphery of a wheel. Each tube is then inverted and returned to its initial position on each revolution of the wheel. The quality of the agitation is good but the automation is limited to the capacity of the wheel, which has to be changed each time capacity is reached. 
     In agitators provided with racks, the tubes are placed in racks before being loaded into an analyser. The analyser then arranges for the agitation of the tubes followed by the analysis and storage of the analysed racks. 
     In order to increase the yield and efficacy of the analyses, it is normal to add automatic conveyor belts to the analysers for carrying the tubes which are to be analysed from a storage zone to the point of analysis where they are taken over by the analyser. 
     The majority of automated lines use a rack-type conveying method with passing means also operating with racks. This technique is used particularly by the company Sysmex, which markets a system in which the racks are mounted on a rail which carries them from one analyser to the other, the passage to an analyser being carried out in a translatory movement. The storage and flow management of the racks are carried out by a buffer storage system. A description of this technique can be found in U.S. Pat. No. 5,232,081. The storage and flow management of the racks are provided by a storage apparatus which makes it possible to adapt the movement of a rack in the storage system on the conveyor to the analysing sequence. The racks have proved effective for analyses which do not require a second passage into the analyser, as they make it possible to achieve high analysis rates. However, this system lacks flexibility if for any reason a tube has to be fed into the analyser a second time. In this case the entire rack containing the tube in question has to be returned to the storage device in order to be sent back into the analyser. 
     The use of racks in an automated line also requires restrictive arrangements in terms of changes of direction and turns required of the conveyor belt. Examples of solutions which set out to solve these problems are described in particular in U.S. Pat. No. 5,366,062 and U.S. Pat. No. 5,380,488. 
     Another problem concerns reading the information written on the label of each of the tubes, owing to the fact that the automated line has to have readers for reading the labels on each tube through the rack. A number of technical solutions have been proposed for solving this problem. Thus, for example, U.S. Pat. No. 6,081,326 and U.S. Pat. No. 5,286,959 describe a device for rotating the tube on itself inside the rack in order to position its label in front of an optical reader positioned in front of a slot in the rack. According to another embodiment described in US Patent Application 2002/0100806, a lug located in the indentation containing the tube enables the label on the tube to be positioned in front of a window in the rack to allow an optical reader to read the contents of the label. These patents clearly show the complexity and difficulty in reading a label on a tube stored in a rack. 
     Moreover, the use of racks in an automated line has its limits when there is a need to manipulate or select a specific tube in order to run a new series of tests on it. The diagnosis and new measuring techniques show that a tube must be capable of being re-tested or undergoing a new series of tests after a first disputed analysis. In this context the automated line using racks is of no value and the use of an automated line with a mono-tube support appears to be better suited to the needs of modern laboratories. 
     Automated lines with a mono-tube support in the majority of cases are lines comprising conveyor belts. Descriptions of this type of line are to be found in U.S. Pat. Nos. 6,374,989 and 5,941,366. In U.S. Pat. No. 5,224,585, the conveyor belt is used as a magnetic support enabling the supports to remain adhered to the belt during both horizontal and vertical movements. 
     In the field of automated lines, and particularly for biochemical apparatus, chaining techniques are also used. However, the reaction times of these apparatus are quite long. A complex chaining system which combines a tube support with a receptacle integrally attached to the chain and allowing a chemical reaction to be carried is described in particular in U.S. Pat. No. 6,358,471. Another chaining system which can be used to convey tubes in order to transport them to a whole blood analyser is described in U.S. Pat. No. 4,944,924. U.S. Pat. No. 5,582,795 also describes a tube chain which combines the tubes with a belt. 
     These chaining techniques are difficult to apply to automated lines, notably because they do not allow for the removal of a tube, or a tube with its support, without producing problems in the flow of tubes. Similarly, returning a tube to one of the apparatus requires the whole chain to run to the apparatus which is to be used. The chain described in the above-mentioned patents appears to be an inflexible technical solution and certainly not adapted to modern automated lines working with whole blood. 
     Other patents or patent applications such as U.S. Pat. No. 5,623,415, U.S. Pat. No. 4,039,288, U.S. Pat. No. 5,623,415, WO 95/03548 and WO 98/01760, describe the use of analytical equipment comprising mono-tube rails, but these appear to be intended solely for conveying tubes and do not disclose any pre-analytical means enabling the tubes to be agitated, for example, before analysis. 
     The category of unitary lines chiefly has the advantage that each tube can be treated as a different entity from the other tubes. To do this it requires that its own needs be met in terms of analysis, checking and additional examination, notably the possibility of easily making use of “conditioned analysis” or “reflex testing” which consists in automatically carrying out complementary examination if this can logically assist the diagnosis. This is a source of effectiveness in arriving at a diagnosis and reducing costs by doing away with any additional examinations which are irrelevant to the diagnosis. 
     BRIEF SUMMARY OF THE INVENTION 
     The invention sets out to introduce, into automated mono-tube lines, dedicated pre-analytical means for tubes of whole blood, enabling each whole blood analyser installed in an automatic line in unitary mode to be connected up as simply as an analyser working on blood serum or plasma. 
     It sets out in particular to transfer the treatment and actions carried out on the sample before it enters a whole blood analyser to the pre-analytical module for transferring it into a tube ready to be analysed in a whole blood analyser. 
     According to this aspect of the invention the whole blood analyser has the characteristics of an analytical terminal, the function of which is restricted to carrying out the analysis itself, like an analyser operating with plasma or whole blood, the mode of operation of which is again the unitary mode. 
     According to another aspect of the invention the pre-analytical module is provided for responding to demands coming from all the whole blood analysers connected to the automated line. 
     Advantageously, the device according to the invention comprises a pre-analytical module arranged on a mono-tube transfer line between a storage zone for the tubes to be analysed and at least one whole blood analyser operating in unitary mode, thus making it possible to combine and optimise the actions and functions needed to prepare the tubes of whole blood before they enter the analyser. 
     Previously, these functions and actions were carried out by the whole blood analyser or manually. The pre-analytical module makes it possible to manage these actions and functions in a logical coordinated manner with the analysers present in the automated line. 
     The pre-analytical module offers greater flexibility in the process of analysis by supplying agitated tubes to the whole blood analyser, but it can also supply a quality control tube for another analyser in a very short time. 
     The pre-analytical module also sets out to make the operations which would otherwise be manual completely automatic, while ensuring that they conform to the standardisation in force in the laboratories. 
     According to a first alternative embodiment the pre-analytical module comprises a device for aerating and recognising the tubes, a tube agitator for homogenising the blood before analysis, and means for automatically loading and unloading the tubes which are disposed respectively between the transfer line and the device for aerating and recognising the tubes and the tube agitator. 
     According to a second alternative embodiment, the pre-analytical module comprises a compartment for preserving and providing quality control tubes for analysers which require monitoring, and a tube agitator for homogenising the blood in the control tubes and in the tubes which are to be analysed, as well as means for automatically loading and unloading the tubes located respectively between the transfer line and, on the one hand, the compartment for preserving and providing the quality control tubes and, on the other hand, the tube agitator. 
     According to a third alternative embodiment resembling the first two, adjoining the tube agitator is a compartment for providing the analyser with quality control tubes and a device for aerating and recognising tubes and also means for automatically loading and unloading the tubes which are located respectively between the transfer line and the compartment for preserving and providing quality control tubes, the device for aerating and recognising the tubes and the tube agitator. 
     In a preferred embodiment, the device for aerating and recognising the tubes comprises a device for piercing the tubes thus aerating them and a reading device for recognising the information marked on the tube labels. 
     The compartment intended for supplying the analyser with quality control tubes comprises an insulating container the interior of which is kept at constant temperature by a regulating module and a switching device for transferring the regulating parameters via a network interface module in order to allow a control and feedback module to receive instructions from a telemaintenance centre or an internet or intranet type information network. 
     According to a preferred embodiment the regulating module is a regulating module of the known Peltier-effect kind. 
     According to another advantageous feature, the transfer line is folded on itself so as to form an ascending track and a descending track and is coupled to a tube exchanger/loader disposed between the pre-analytical module and the analyser which enables the tubes either to be transferred from one track to the other or to overtake the tube in front of them on the same track. 
     In this embodiment the tube exchanger/loader device separates each of the two tracks into two sections and is made up of a drawer divided into four compartments, the drawer being movable in translation in a direction perpendicular to the longitudinal axis of the conveying rail. In this way it is possible for a tube to be transferred from one track to the other by positioning the compartment which contains it between the two sections of the other track. 
     The movement of a tube in front of another one on the same track is achieved by positioning the compartment containing the tube which is to be overtaken outside its track, thus enabling the tube behind it on the same track to occupy the adjacent compartment, in a first stage, before continuing its progress on the same track, in a second stage. 
     To allow automatic loading/unloading of the tubes between the conveying line and the pre-analytical module, the conveying line is divided up into sections consisting of conveyor belts separated from one another by loading/unloading devices in the form of drawers divided into compartments limited by two partitions arranged parallel to the longitudinal direction XX′ of the conveying rail and of such dimensions as to accommodate a tube and its support in each case. 
     In a preferred embodiment the loading and unloading devices in the form of a drawer are divided into three compartments, an end compartment for loading and unloading the tubes in the pre-analytical module and two compartments dedicated to transferring tubes between the two adjacent sections of the ascending track and descending track, respectively. 
     In order to achieve an optimum operating rate for the agitator and comply with the conditions set down by the NCCLS for use in laboratories, the agitator comprises a wheel provided with a specified number of indentations each capable of accommodating a tube, each tube to be agitated being loaded into an indentation by a loading device. 
     Finally, to allow automatic loading of the tubes from the storage zone onto the transfer line, the storage zone comprises a manipulating arm which assigns each tube on a conveyor to a support. The tubes with their supports are then transported by the conveyor along the conveying line. 
     It is advantageous if the pre-analytical module comprises, in addition to the tube agitator, a detector for detecting the level of liquid contained in a tube. 
     The pre-analytical module may also comprise in addition to the tube agitator a heating means for heating the tubes on the tube agitator by the Peltier effect. 
     The preserving compartment mentioned above may also contain tubes intended for analysis. The pre-analytical module may also comprise several storage compartments intended for quality control tubes or tubes intended for analysis. 
     According to yet another feature of the invention the pre-analytical module comprises a detector for detecting the presence of clots in the tubes of blood. This detector preferably comprises optical means or sound waves or electrical means. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the description that follows which is provided solely by way of example, reference is made to accompanying drawings, wherein: 
         FIG. 1  is a plan view of an embodiment of a device according to the invention which allows tubes of blood to be supplied automatically to a mono-tube whole blood analyser; 
         FIG. 2  shows part of the device of  FIG. 1  on an enlarged scale; 
         FIG. 3  is a front view corresponding to  FIG. 2 ; 
         FIG. 4  is a perspective view of a robot arm for gripping the tubes between the storage zone and the transfer line provided in the device shown in  FIGS. 1 and 2 ; 
         FIG. 5  is a view showing an embodiment of a tube support member fitted to the transfer line in  FIGS. 1 to 3 ; 
         FIG. 6  is an embodiment of the preserving compartment provided on the device in  FIGS. 1 to 3 ; 
         FIGS. 7 and 8  are two view showing two alternative embodiments of a device according to the invention; 
         FIG. 9  is a flow chart illustrating a method of operation of a device according to the invention; 
         FIGS. 10 and 11  are a plan view and front view of a liquid level detector; 
         FIG. 12  is a front view of a tube agitator provided with a Peltier-effect heating member; 
         FIG. 13  is a plan view of a storage compartment analogous to that in  FIG. 6  intended for quality control tubes or tubes intended for analysis; and 
         FIGS. 14 and 15  are a plan view and a front view of a detector intended to identify the presence of clots inside a tube. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Reference will be made first of all to  FIGS. 1 to 3  in which corresponding elements have been given the same reference numerals and which show a first embodiment of a device according to the invention. This device comprises a pre-analytical module  1  arranged between a storage zone  2  for the tubes of blood to be analysed and at least one mono-tube analyser  3 . A mono-tube conveying line  4  in the form of a rail transports the tubes  5  from the storage zone  2  to their destination, either from the pre-analytical module  1  or from one or more mono-tube analysers  3 . By the term “mono-tube” is meant that the operation in question (conveying, analysis, etc.) is carried out on an individual tube and not on a plurality of tubes. 
     The pre-analytical module  1  is intended to perform a certain number of operations prior to a subsequent analysis. It is made up of a device  6  for aerating and recognising tubes  5 , a compartment  7  for storing and providing quality control tubes, and an agitator  8  which, in the embodiment shown, allows the tubes to be agitated simultaneously by means of three wheels  8   a ,  8   b  and  8   c  rotatably mounted about a horizontal axis. The storage compartment  7  may also contain tubes  5  intended for analysis. 
     The pre-analytical module  1  also comprises a control and feedback module  9   a  ( FIGS. 1 and 2 ) coupled to a keyboard  9   b  and a display screen  9   c  ( FIG. 3 ). The latter make it possible to monitor and observe the operation of the elements that make up the pre-analytical module  1 . The control and feedback module  9   a  is furthermore coupled to a network interface module  10  enabling the control and feedback module  9   a  to receive instructions from a telemaintenance centre (not shown) through an internet or intranet type information network, for example. 
     The storage zone  2  ( FIG. 1 ) comprises a zone  2   a  for storing the tubes  5  which are to be analysed, a zone  2   b  for storing supports  11  for tubes  5  and an assembly zone  2   c  intended for assembling the tubes  5  which are to be analysed on their supports  11  and enabling the tubes which are to be analysed to be transported with their supports on a conveyor  12  folded in a zigzag configuration towards the conveying rail  4 . The combining of the tubes  5  with their supports  11  is carried out as shown in  FIG. 4 , using a robot manipulating arm  13  which assigns a tube  5  to be analysed, which is located in the storage zone  2   a  for the tubes, to a support  11  in the storage zone  2   b  for the supports, on the conveyor  12  in the assembly zone  2   c.    
     As shown in  FIG. 5 , the tubes  5  are provided with individual stoppers  14  and are placed vertically inside a support  11  where they are held by spring plates  15 . 
     The analyser  3  comprises, in known manner, a blood analysing device  16  coupled with sampling means  17  comprising an indentation  19  for holding each tube  5  which is to be analysed in alignment with a sampling needle  20 . The analyser  3  also comprises means  21  for controlling the analysing device, coupled with a keyboard  22  and a monitoring screen  23 . 
     Advantageously, the mono-tube conveying line  4  is folded on itself so as to form two parallel tracks  4   a ,  4   b  moving in opposite directions to one another and comprises a tube exchanging/loading device  24  disposed across the two tracks  4   a  and  4   b  in order to allow tubes to be transferred between the two tracks or to enable a tube on one track to overtake the tube in front of it on the same track. 
     The first track  4   a , hereinafter referred to as the ascending track, moves the tubes  5  from the storage zone  2   c  towards the analyser  3  and the second track  4   b , or descending track, moves them in the opposite direction between the analyser and the storage zone  2 . 
     To allow the tubes mounted on their supports to be loaded onto the conveying rail or to be unloaded into the different modules that make up the pre-analytical module  1  and in the analyser  3 , the conveying line  4  is divided up into sections designated T 1   a  to T 6   a  on the first track  4   a  and T 1   b  to T 6   b  on the second track  4   b , separated from one another by loading/unloading devices designated  25  to  30  in the form of drawers divided into compartments  25   a ,  25   b ,  25   c ; . . . ;  30   a ,  30   b ,  30   c.    
     Each section  25   a ,  25   b ,  25   c ; . . . ;  30   a ,  30   b ,  30   c  of the conveying line  4  is in the form of a conveyor belt moving between two side walls  31   a ,  32   a ;  31   b ,  32   b , respectively. The compartments  25   a ,  25   b ,  25   c ; . . . ;  30   a ,  30   b ,  30   c  of each of the loading/unloading devices are aligned in a direction perpendicular to the longitudinal axis XX′ of the conveying rail  4  and are dimensioned so as to each accommodate a tube  5  and its support  11  coming from the section of rail adjacent thereto. 
     To allow a tube  5  with its support  11  to fit into a compartment, each compartment has a base  33  located in the same plane as that of the two conveyor belts belonging to the two sections of rail adjacent thereto and limited by two partitions  34 ,  35  perpendicular to said base  33  and aligned respectively with the side walls  31  and  32  which delimit the conveyor belts of sections T 1   a  to T 6   a  and T 1   b  to T 6   b  of the conveying line  4 . The movement of the tube supports  11  in the compartment is ensured by drive rollers  36  in contact with the tube supports  11 . 
     The tube exchanger/loader  24  is also in the form of a drawer which is movable in translation in a direction perpendicular to the longitudinal axis XX′ of the conveying rail  4 . Unlike the loading/unloading devices, it is made up of four compartments  24   a ,  24   b ,  24   c ,  24   d  comprising, in a similar manner to those of the loading/unloading device, a base  37  bounded by two partitions  38 ,  39  perpendicular to the base  37  and extending in the direction of the longitudinal axis XX′ of the conveying line  4 . The transfer of a tube  5  from one track to the other is effected by moving the tube exchanger/loader device  24  in the direction perpendicular to the longitudinal axis XX′ of the conveying rail  4 , aligning the partitions of the compartment containing the tube from a track which is to be transferred respectively with the side walls  31  and  32  of the other track. This manoeuvre, which takes place under the control of the control and feedback device  9 , makes it possible to reverse the direction of travel of a tube  5  and its support  11  on the conveying rail  4 . However, it is also possible to move a tube  5  and its support  11  outside the track on which they are travelling by placing the tube  5  and its support  11  in a compartment  24   a ,  24   d , respectively, located at one end of the drawer in order to allow the tube and its support travelling behind it on the same track to move into the respectively adjacent compartment  24   b ,  24   c  in order to overtake them on the same track. 
     The tube aerating and recognising device  6  and the compartment  7  are supplied with tubes by the mono-tube conveying line  4  using the loading/unloading devices  25  and  26 . 
     The loading/unloading device  26  makes it possible either to transfer tubes continuously onto each of the tracks  4   a ,  4   b , without going via the tube aerating and recognising device  6 , or to pick up a tube  5  from the track  4   a  in order to transfer it into the tube aerating and recognising device, in a position enabling it to be pierced by a piercing device  40  ( FIG. 3 ) for aerating it and enabling its marking to be recognised by the reading of the data characterising it, marked on a label attached to the tube  5 , by a suitable reader (not shown). This information tells the analyser, in particular, what kind of analysis and what kind of action it has to carry out on the contents of each tube. Once the tube has been aerated and identified it is brought along on the conveying rail  4  to be steered either to the agitator  8  or directly to the analyser  3 . 
     The compartment  7  which is intended for storing and managing control bloods, contains a specified number of tube emplacements  41   i  ( FIG. 2 ) arranged on a belt  42  which supplies the conveying rail  4  via the loading/unloading device  25  to allow either continuous transfer of the tubes onto each of the tracks  4   a ,  4   b  or in order to pick up a tube from the belt  42  to transfer it to the track  4   a  of the conveying rail or vice versa in order to pick up a tube from one of the tracks  4   a ,  4   b  of the conveying rail to transfer it into a free emplacement  41   i  on the belt  42 . 
     In the embodiment shown in  FIG. 6 , the compartment  7  has an insulating container  43  the interior of which is kept at a constant temperature by a regulating module  44  of the known kind operating by the Peltier effect, for example. It also comprises a switching device  45  for transferring the regulating parameters to the network interface module  10  in  FIGS. 1 and 2 . The tubes  5  are held on the belt  42  by mechanical or magnetic fixing means  46  controlled by the control and feedback device  9 . 
     In the configuration in  FIGS. 1 to 3 , the agitator  8  agitates three tubes simultaneously by means of the indentations in three wheels  8   a ,  8   b ,  8   c  which are respectively supplied by three loading/unloading devices  27 ,  28 ,  29 . However, this number may equally well be reduced as increased as a function of, on the one hand, the capacity of the analyser or analysers to be served and, on the other hand, taking account of the minimum agitation time for the tubes which is needed to re-suspend the blood cells for analysis in each tube to a satisfactory extent. 
     The exemplary embodiments of the device according to the invention shown in  FIGS. 7 and 8  show the different versions of the embodiment in  FIGS. 1 to 3 . In the second alternative embodiment of the device shown in  FIG. 7  in which the elements corresponding to those in  FIGS. 1 to 3  bear the same reference numerals, the pre-analytical module  1  has the same elements as in  FIGS. 1 to 3  but without the device  6  for aerating and recognising the tubes. This more simplified system is more particularly suitable for carrying out control operations on the analysers. 
     According to the third alternative embodiment of the invention shown in  FIG. 8 , in which elements corresponding to those in  FIGS. 1 and 2  bear the same reference numerals, the pre-analytical module is formed solely by a device  6  for aerating and recognising the tubes and a module  8  for agitating the tubes in order to homogenise the blood and prevent clotting. 
       FIG. 9  describes a method of operation of the pre-analytical module  1  starting from a request for analysis which may come from four different users. In the example shown the request may come from a workstation  46 , a whole blood analysing module  47  which is present or connected to the automated line  4 , a manual request  48  sent by an operator using the interface of the pre-analytical module  1  wishing to undertake maintenance action, for example, and finally a request  49  coming from the network through the intranet or internet of a telemaintenance centre to initialise the launch of quality control, for example. 
     When a request is received at step  50  by the pre-analytical module  1  it is interpreted at step  51  in order to verify the validity of the request. Then in step  52  a record of the actions programmed and taking place is drawn up in order to check that the pre-analytical module  1  actually has the capacity to deal with the new request within a specified period. Once the analysis is complete and if the conditions of acceptance of the new request have been met the pre-analytical module integrates the new request in its planning, in step  53 , in accordance with its priorities. Then the pre-analytical module continues to execute the requests, taking account of its new plan updated by accepting the new request to launch pre-analytical actions in step  54 . Next, the pre-analytical module  1  reports in step  55  its new state to the issuer of the request. 
     In the embodiment shown in  FIGS. 10 and 11 , the pre-analytical module comprises, in addition to the tube agitator, a detector  56  designed to detect the level of a liquid contained in a tube  5 . In the example this detector  56  is combined with sampling means  17  analogous to those described previously. The detector  56  comprises an emitter  57  designed to emit a light wave and a receptor  58  designed to receive the light wave which has passed through the tube, thereby determining the level of liquid contained in the tube. 
       FIG. 12  shows a tube agitator  8  comprising three wheels  8   a ,  8   b  and  8   c , each of which carries a heater  59  for heating the tubes  5  on the tube agitator. In the embodiment shown the heaters  59  are each made in the form of a plate operating by the Peltier effect. 
       FIG. 13  shows a storage compartment  60  analogous to the one described previously with reference to  FIG. 6 , but the insulating container  43  of the compartment is provided in this case to accommodate the tubes  5  intended for analysis. Generally speaking, the pre-analytical module  1  may comprise several storage compartments  7  or  60  intended for quality control tubes or for tubes which are intended for analysis. In the embodiments shown in  FIGS. 14 and 15 , the pre-analytical module comprises detectors  61   a ,  61   b ,  61   c ,  61   d ,  61   e  and  61   f  arranged to detect the presence of clots in the tubes of blood  5 . These six detectors may comprise optical means or sound waves or electrical means.