Centrifuge for separating of whole blood into blood components as well as fluidically communicating containers for insertion into the centrifuge, as well as a method for obtaining a highly enriched thrombocyte concentrate out of whole blood

The invention refers to a centrifuge for separating whole blood into its blood components and a method for extracting a highly enriched thrombocyte concentrate out of whole blood. For this purpose, the centrifuge comprises a closed loop and/or open-loop control unit as well as a drive unit coupled to the closed loop and/or open-loop control unit, a rotor (12) having at least two container receptacles (14a, 14b; 16a, 16) for removably holding containers (18, 20, 22, 24) being in fluid communication with each other, at least one sensor arranged between the container receptacles (14a, 14b; 16a, 16b) and coupled with the closed loop and/or open-loop control unit for detecting a separation layer. Herein, a motor/gear unit (30a, 30b, 32a, 32b) coupled to the closed loop and/or open-loop control unit is associated with each of the container receptacles (14a, 14b; 16a, 16b). Each of the motor/gear units is in operational contact through means (34) with each of the containers (18, 20, 22, 24) supported in the respective container receptacle (14a, 14b; 16a, 16b) such that a transfer and back-transfer of blood components between the containers (18, 20, 22, 24) is initiated.

This application claims priority to German patent application no. 10 2009 040 525.9-23 filed Sep. 8, 2009, which is incorporated herein in its entirety by reference hereto.

The invention refers to a centrifuge for separating whole blood into its blood components. The invention also refers to fluidically communicating containers for insertion into the centrifuge. The invention also refers to a method for obtaining a highly enriched thrombocyte concentrate out of whole blood by means of the centrifuge.

The extraction of a highly enriched thrombocyte concentrate out of whole blood is basically known. For this purpose, the whole blood is separated into erythrocytes having a high density and thrombocytes or platelet rich plasma in a first centrifuge process by means of a centrifuge. An intermediate layer out of leukocytes forms a separation layer between the erythrocytes and the thrombocytes or platelet rich plasma, respectively. In a subsequent second centrifugation process, the thrombocyte or platelet rich plasma, respectively, is then separated into thrombocyte depleted plasma and the desired thrombocyte concentrate.

From EP 1 637 172 B1, a method for separating of blood components contained in bags is known. After separation of the whole blood into erythrocytes and thrombocyte rich blood plasma, it is basically possible with the disclosed apparatus to further process the thrombocyte rich blood plasma and, thereby, the extraction of thrombocyte concentrate. Besides a centrifuge for centrifugation, according to the teaching of EP 1 637 172 B1, a further apparatus is provided therein for squeezing-off. The required switching between centrifuge at the one hand and the squeezing-off device on the other hand, proves to be cumbersome and time consuming.

The invention is based on the objective to provide a centrifuge which allows a simplified production of a highly enriched thrombocyte concentrate.

According to the invention, the centrifuge for separating whole blood into its blood components comprises a closed loop and/or open-loop control unit as well as a drive unit coupled to the closed loop and/or open-loop control unit, a rotor having at least two container receptacles for removably supporting fluidically communicating containers, as well as at least one sensor arranged between the container receptacles and coupled to the closed loop and/or open-loop control unit for detecting a separation layer. Each motor/gear unit is coupled to the closed loop control unit and/or each motor/gear unit is coupled to an open-loop control unit. The closed loop control unit and/or the open loop control unit is/are associated with the container receptacles. The motor/gear units are in operational relationship with the containers supported in the respective container receptacles by means such that a transfer and back-transfer of blood components between the containers is initiated. In an advantageous manner, it is now possible by means of the inventive centrifuge to carry out an automatic transfer and back-transfer of blood components between the containers in the centrifuge. Since it is not necessary to remove one of the two containers, an undesired, subsequent intermixture is excluded such that the production of a highly enriched blood component, in particular the production of a highly enriched thrombocyte concentrate, is ensured. As already mentioned, since the containers remain in the centrifuge during a transfer or a back-transfer, respectively, of blood components between the containers, there is additionally ensured a simplified handling, a shortened processing time as well as a reproducible extraction of thrombocyte concentrate having defined, high quality features.

According to a particularly advantageous embodiment of the invention, the rotor comprises at least two container receptacle pairs comprising two container receptacles each for removably supporting two containers each being in fluid communication with each other, wherein a sensor for detecting a separation layer is arranged between each container receptacle pair. The container receptacle pairs are closed systems for the sterile processing of blood samples. The pair-wise arrangement of two containers proves to be advantageous since optimal loading and smooth operation of the centrifuge optimal separation results.

Preferably, a further sensor is associated with each container receptacle pair. The sensor can detect if the proper container receptacle type is being used. Providing the further sensor has the positive effect that improper container receptacles may be in use and, thereby, an unbalance may be detected ahead of time.

In order to ensure a cost-effective and reliable detection of the separation layer or the type of equipment being used in a container receptacle pair, respectively, the sensors are embodied as optical sensors.

For ensuring a low-noise data- and energy transfer, the centrifuge comprises an inductive interface for an inductive transfer of data and energy.

The invention is furthermore based on the object to provide fluidically communicating containers in the centrifuge which ensure good efficiency and simplified handling.

According to the invention, the fluidically communicating containers form a closed system for the sterile processing of blood samples, and the containers are each formed in the shape of a tubule having a piston moveably arranged in the interior of the tubule, wherein the tubules are in operational connection with the motor/gear unit associated with the respective container receptacle, by a push rod being in removable contact with the piston. The arrangement of the container according to the invention proves to be particularly advantageous since the tubules do not comprise sediment nests because of their strong structure, and, thereby, good efficiency is ensured. Since the pistons are arranged in the tubules, the coupling, by means of the push rod with the related motor/gear unit of the centrifuge enables simple handling.

According to a particularly advantageous embodiment of the invention, at least in one of the tubules, the piston is formed in two parts comprising, as seen in the inward movement direction of the piston, a forward piston portion and a rearward piston portion. Therein, the forward and rearward piston portion are removably connected to each other, and the rearward piston portion comprises a through bore closed by a seal such that, by disconnecting the two piston portions, the forward piston portion may be moved relative to the rearward piston portion by means of a piston rod insertable through the through bore in the rearward piston portion. The two-part arrangement of the piston proves to be particularly advantageous since, thereby, a targeted intermixture of the blood component contained in this area of the tubule is possible by means of an upwards and downwards movement of the forward piston portion.

Therein, the rearward and forward piston portion are preferably removably connected to each other by means of a bayonet coupling, and the forward piston portion comprises a bore with an interior thread, and the piston rod comprises, in its forward portion, an outer thread formed correspondingly thereto. The arrangement of the removable connection by means of a bayonet coupling as well as the provision of a screw connection between the piston rod and the forward piston portion proves to be particular advantageous since the bayonet coupling as well as the threading between the piston rod and the forward piston portion may be operated by means of a turning movement. For example, the piston rod may be connected to the forward piston portion by means of a rotation in the clockwise direction, whereas—after the piston rod is fixedly connected to the forward piston portion—a subsequent rotation in the anti-clockwise direction effects disconnection of the bayonet coupling.

In order to ensure an effective detection of the separation layer by means of the optical sensor, the two tubules are connected in fluid communication with each other by means of a transparent hose.

According to a further embodiment, two or more tubules are connected in fluid communication with each other by means of a transparent hose which is divided up by a coupling element into two or more hose lines each having a check valve. For example, if one tubule is filled with whole blood and fluidically connected with two further tubules by means of a hose comprising a coupling element, besides the separation of the whole blood into its blood components also a transfer of the separated blood components into two separate tubules is made possible now in an advantageous way.

Preferably, the hose comprises an integrated valve. The integration of the valve has the effect that an undesired backflow is prohibited thereby during the centrifugation or after a centrifugation process, respectively.

According to a further advantageous embodiment of the invention, the hose comprises, at its end, connection elements by which the hose is adapted to be removably connected through the closure caps of the tubules. Provision of the connection elements proves to be advantageous since handling is made simple.

The invention is furthermore based on the object to provide a method for extracting a highly enriched thrombocyte concentrate out of whole blood.

The method of the invention comprises the following steps:Inserting at least two tubules fluidically connected to each other by a hose, into the container receptacles where the first tubule contains the whole blood and the second tubule, named secondary tubule in the following, contains a biocompatible material if needed;Providing an operational connection between the pistons located in the tubules, and the related motor/gear units by means of a push rod;Initiating movement of the centrifuge with a first centrifuge speed;First centrifugation until an erythrocyte concentrate having a high density as well as a thrombocyte enriched blood plasma separated there from by a separation layer have formed in the first tubule;Reducing the centrifuge speed to a first squeezing-off speed;Starting movement of the motor/gear unit associated with the first tubule and being in operational connection with the piston, and squeezing-off the thrombocyte enriched blood plasma through the hose into the secondary tubule until the sensor has detected the separation layer;Increasing the speed to a second centrifuge speed;Second centrifugation until a thrombocyte concentrate with higher density as well as separated thrombocyte depleted blood plasma have formed in the secondary tubule;Reducing the centrifuge speed to a second squeezing-off speed;Starting movement of the motor/gear unit associated with the secondary tubule and being in operational connection with the piston, and squeezing back the thrombocyte depleted blood plasma into the first tubule;Breaking down the centrifuge;Slowing down the motor/gear units;Removing the tubules.

Since, according to the method of the invention, the thrombocyte depleted blood plasma is removed prior to removing the secondary tubule out of the secondary tubule receptacle, the repeated intermixing is excluded such that, in an advantageous way, a highly enriched thrombocyte concentrate can be produced by means of the method of the invention.

Preferably, all method steps are automated, i.e. carried out according to a prior defined running scheme, except the steps of inserting and removing the tubules. Since the parameters for the first centrifugation (time, speed or RCF/radius, speeding up and breaking down ramps), the first squeezing-off speed, the parameter for the second centrifugation (time, speed or RCF/radius, speeding up and breaking down ramps), the second squeezing-off speed, the back squeezing volume on the back squeezing process as well as the breaking down ramp for breaking down the centrifuge are carried out according to a pre-defined running scheme, faulty operation by the operators is almost excluded.

Therein, the above-mentioned parameters may be input, with the centrifuge in still stand, in a comfortable way by the operators into the closed loop and/or open-loop control unit or may be changed or may be adapted to the respective application, respectively.

In particular for the case that the secondary tubule has a biocompatible material contained therein, according to a particularly advantageous embodiment of the method for producing the thrombocyte concentrate, the secondary tubule is used having a two-part piston, and, after removing the secondary tubule from the centrifuge, the contents of the secondary tubule, i.e. the biocompatible material and the thrombocyte concentrate, are mixed by means of the forward piston portion. This has the effect that, if the application requires this, a homogenous paste out of thrombocyte concentrate and biocompatible material can be obtained for filling up defects. This is subsequently applied into the defect.

Further advantageous features and application possibilities of the present invention result from the following specification in connection with the embodiment shown in the drawing.

In the following, the invention is described with reference to the embodiment shown in the drawing, in the specification, in the claims and the drawing the terms contained in the list of reference signs given below and the related reference signs are used. In the drawings:

In the following specification and in the figures, the same parts and components are characterized by the same reference signs for avoiding repetition as far as no further differentiation is necessary or makes sense.

DESCRIPTION OF THE INVENTION

FIG. 1shows in a perspective view, a centrifuge all together provided with the reference number10. Out of reasons of clarity, at present only a centrifuge head11and a rotor12is shown here assembled onto the centrifuge head11. The associated closed loop and/or open-loop control unit as well as the drive unit for the centrifuge10are also not shown in the perspective view ofFIG. 1out of reasons of clarity, rather, they are schematically illustrated inFIG. 1A.

FIG. 1Ais a diagrammatic view of the open and/or closed loop control unit, the first optical sensor, the second optical sensor, the third optical sensor, the fourth optical sensor, the fifth optical sensor, the sixth optical sensor, and the inductive interface and the drive unit.

The rotor12comprises all together four container receptacles14a,14bas well as16a,16b. The two container receptacles14aand14bare named in the following simply as container receptacle pair14, and the container receptacles16aand16bas container receptacle pair16. Within each container receptacle pair14,16, there is contained a pair of containers each connected in fluid communication with each other in form of a tubule having a piston which is movably arranged in the interior of the tubule. For example, container receptacle pair14and, in particular, the container receptacle14aincludes tubule18.

Accordingly, the container receptacle pair16comprises in the container receptacle16aa tubule22and in the container receptacle16ba secondary tubule24. The tubules18,20are connected to each other in fluid communication through a transparent hose26and form a closed system for the sterile processing of blood samples. The tubules22,24are connected to each other in fluid communication through a transparent hose28and form a closed system for the sterile processing of blood samples.

As can be taken fromFIG. 1, furthermore, the tubules18,20,22,24are radially aligned, and the transparent hoses26,28are guided in a central unit. Optical sensors S1, S2for detecting a separation layer arising in the hose are associated with each hose26,28. First optical sensor S1and second optical sensor S2detect separation layers. Furthermore, the presence of a hose is monitored by means of optical sensors S3, S4which are associated with each of the hoses26,28. Third optical sensor S3and fourth optical sensor S4detect the presence of hoses26,28. The sensors S1and S2are illustrated inFIG. 1between respective pairs of container/tubule receptacles. S3and S4are illustrated inFIG. 1between respective pairs of container/tubule receptacles.

Preferably, a fifth sensor S5and a second sensor S6are associated with each container receptacle pair. Sensors S5, S6can detect if the proper container receptacle type is being used. Providing sensors S5, S6has the positive effect that improper container receptacles may be in use and, thereby, an unbalance may be detected ahead of time.

As can be furthermore taken fromFIG. 1, motor/gear units30a,30b,32a,32bare associated with respective container receptacles14a,14b,16a,16bdisposed radially outwardly and are in operational connection by means of a push rod with the piston arranged in the respective tubule. Out of reasons of clarity only one push rod34is shown here at the motor/gear unit30a.

FIG. 2shows the rotor head11after removal of the rotor12. Herein, the motor/gear units30a,30b,32a,32bare here shown again in detail.

FIG. 3shows, in an enlarged presentation, the tubules18and20contained in the first container receptacle pair14. As can be taken fromFIG. 3, the tubules18,20each comprise a removable closure cap36,38, while the transparent hose26is provided, at its ends, with connection elements40,42. By means of the respectively associated elements, closure cap/connection element36/40and/or38/42, respectively, the fluid connection between the tubules18,20can be established by means of the hose26in a simple manner. Whereas the tubule18serves for receiving the whole blood, the secondary tubule20is provided for receiving the separated blood component. The arrangement of the tubules22,24contained in the second container receptacle pair16is accordingly.

The transparent hose26is again shown inFIG. 4with the associated connection elements40,42.

FIG. 5shows the secondary tubule20,24, once in a mounted and once in a demounted state. As can be taken from the exploded view, the tubule20,24comprises a two-part piston44.

The two-part piston44comprises a backward piston portion46as viewed in the screwing-in direction, as well as a forward piston portion48which are removably connectable to each other by means of a bayonet coupling50. Furthermore, the backward piston portion48comprises a through bore closed by a seal. Furthermore, a piston rod which has an outer thread54in its forward area, is associated with the secondary tubule20or24, respectively.

It is ensured thereby that, after finishing the centrifugation and after removal of the secondary tubules20,24out of the centrifuge, a mixing of the blood component contained in the secondary tubule20,24may be carried out. For this purpose, the piston rod52is inserted into the secondary tubule22,24, and it is pushed through the through bore contained in the backward piston portion46and is subsequently screwed into the forward piston portion48. After the connection between the piston rod52and the forward piston element48has been made, the bayonet coupling50is disconnected by a further rotation, and the forward piston portion48is separated from the backward piston portion46. By means of an upwards and downwards movement of the forward piston portion48with respect to the backward piston portion46, the blood component contained therein, is manually mixed with the optionally present biocompatible material. After the mixing procedure, the forward piston portion48is retracted by means of the piston rod52and again fixed to the backward piston portion46.

With the centrifuge10, the production of a highly enriched thrombocyte concentrate out of whole blood or a paste out of biocompatible material and thrombocyte concentrate is possible in an advantageous way.

For this purpose, a first tubule18filled with whole blood as well as a secondary tubule20which optionally contains the biocompatible material, are inserted into the first container receptacle pair14. A tubule22filled with whole blood and having the same weight, and its associated secondary tubule24also optionally containing a biocompatible material, are inserted into the second container receptacle pair16.

Because of the hose detection sensor, a not inserted second container pair and, thereby, an unbalance, would be detected early in time.

After the tubules18,20as well as22,24have been inserted, a start-up of the centrifuge10is effected. The first centrifugation process lasts until the erythrocyte concentrate with high density as well as thrombocyte enriched blood plasma separated there from by a separation layer have been formed in the tubules18,22.

Subsequently, the speed of the centrifuge10is reduced, and the motor/gear units30a,32aassociated with the tubule18and the tubule22, respectively, are started up and move by means of the associated push rods the piston contained in the tubules18,22. This means that a squeezing-off of the thrombocyte enriched blood plasma is effected through the transparent hose26,28into the associated secondary tubules20,24which, as already stated, optionally contains a biocompatible material. The squeezing-off process lasts until the separation layer is detected in the transparent hose26,28by the associated sensor.

Subsequently, the speed of the centrifuge10is put up again and a second centrifugation process is effected. The second centrifugation process lasts until a thrombocyte concentrate with higher density as well as thrombocyte depleted blood plasma has been formed in the secondary tubules22,24.

Subsequently, the speed is reduced again, and the motor/gear units30b,32bassociated with the secondary tubule22,24are starting to move. A squeezing-off of a pre-defined volume element out of the secondary tubule22,24follows through the hose26,28into the tubules18,20such that a highly enriched thrombocyte concentrate remains in the secondary tubules22,24.

After breaking down the centrifuge and after slowing down the motor/gear units30a,30b,32aand32b, the tubules18,20,22,24can be subsequently removed.

In a further processing step, a piston rod52is inserted optionally into each of the secondary tubules20,24. By fixing of the piston rod52at the forward piston portion48and loosening of the bayonet coupling50in the above described manner, a mixing of the highly enriched thrombocyte concentrate contained in the secondary tubules with the optionally already provided biocompatible material out into a homogenous paste is carried.

Subsequently, the removal of the highly enriched thrombocyte concentrate or the paste, respectively, out of the secondary tubules20,24is effected by the squeezing-off process.

LIST OF REFERENCE SIGNS

Those skilled in the art will recognize that the invention has been set forth by way of example herein and that changes may be made to the invention without departing from the spirit and scope of the claims set forth hereinafter.