This invention also relates to a blood component sepa- rating device which comprises a centrifuge member adapted for rotation about its central axis in a centrifuge, said member having two outer, respectively inner circular walls substantially parallel to said central axis, solid together in rotation, spaced from each other to define a separating room of rectangular cross-section comprising an inlet open- ing to be connected to a supply of blood or any liquid con- taining human cells and at least two outlet openings, an outlet opening to be connected to means for collecting a higher density component of blood, another outlet opening to be connected to means for collecting a lower density compo- nent, said inlet and other outlet openings being respective- ly adjacent to two upstream, respectively downstream ends angularly spaced of said separating room.

This invention still relates to a process for obtaining the separating device.

Conventional blood processing devices and methods use centrifuge circular disposable chambers into which whole blood is introduced while rotating them to create a centri- fugal field.

Whole blood submitted to the force of the centrifugal field resulting from the rotation of the chamber, separates into higher density red blood cells (RBC) and lower density platelet-rich plasma. (PRP). An intermediate layer of white blood cells is formed between the red blood cells and platelet-rich plasma.

In order to obtain a good platelet recovery efficency (the ratio between the collected platelets (PLT) and the platelets in the whole blood), it is necessary to take them out from RBC and from plasma. For taking out PLT from RBC, RBC have to be concentrated to a maximum, since the collec- tion of platelets is proportionnal to plasma caught between the RBC. In the known separation chambers, 2/3 to 3/4 of its overall length is used for. concentrating RBC to a maximum.

The separation under the influence of centrifugal, force field results in a concentration of RBC against the outer wall of the circular chamber, whereas the platelets are dri- ven into the platelet-rich plasma which is along the inner wall.

The peripheral length of the circular separating cham- ber is determined by the sedimentation paths of platelets into the plasma, the platelet sedimentation speed being 15 times slower than that of RBC. Therefore, if it would be possible to shorten the sedimentation paths of platelets, the length of the separating chamber and thus its diameter could also be proportionally reduced.

Indeed, as it will be explained hereunder, if we take into account a platelet path in the worst operating condi- tions, that is to say that when the platelet is the smallest and when it is released from RBC on the smallest radius of the rotating path where the centrifugal force is the weakest, such a platelet path forms a boundary line between on the one hand, the platelet-poor plasma (PPP) on the inner

side of said path and on the other hand, the platelet-rich plasma (PRP) on the outer side of said path.

WO 94/06535 has already proposed an apparatus and me- thod for fractionating a liquid mixture into liquid frac- tions whose components have different velocities. The appa- ratus comprises a rotating cylindrical assembly having inner and outer shells definig therebetween a tubular gap. One shell includes a porous structure for permeation there- through of one or more of the liquid fractions.

The method and apparatus according to WO 94/06535 requires that blood, or other liquid mixture, enter the spinning"film"at one end, preferably the top of cylindri- cal assembly and move axially, downwardly in laminar stream flow toward an exit which is at the bottom of the cylindri- cal assembly, which is rotated at a speed effective to impart sufficient centrifugal force to a liquid fraction to maintain one of such fraction within the gap while compel- ling flow of the other liquid fraction radially inwardly through the porous structure.

The axial dimension of a such rotating cylindrical as- sembly is substantially longer than its diameter, so that it is not well adapted to allow the connection between an angu- larly rotating input of blood and output of separated compo- nents solid with the central axis of the rotating cylindri- cal assembly and a stationary supply of blood and collector means of liquid fractions by using a flexible conduits according to the same concept as that disclosed in US 3'586'413 for providing energy communication between a rotating and a stationary part. Rotating seals have to be used for connecting such a rotating cylindrical assembly to stationary supply of blood and collector means of liquid fraction, so that the practical problems to be solved are

very complicated. and not at all adapted for producing a separating device with disposable rotating member.

The problem underlying the present invention is to provide a method and device according to which it is possi- ble to substantially reduce the length of the platelet paths, to correspondingly increase the sedimentation speed as well as to improve the platelet recovery efficency. The purpose of the proposed method and device is also to overco- me, at least partially, the drawbacks of the above-mention- ned prior art.

An object of this invention is a method of continuously separating whole blood as well as any liquid containing human cells according to claim 1 Another object of this invention is a separating device of the above-mentionned type according to claim 6.

A third object of this invention is a process for obtaining the separated device according to claim 16.

The present invention will be explained hereafter with reference to the drawings wherein: Figure 1 is a platelet path diagram in a flow of plasma submitted to centrifugal force; Figure 2 is a platelet path diagram in a flow of plasma submitted to a centrifugal force with suction of plasma on the inner side of the platelet path; Figure 3 is a sectional view according to line III-III of figure 4 of an embodiment for carrying out the method according to the invention; Figure 4 is a sectional view according to line IV-IV of figure 3; Figure 5 is a plan view of another embodiment for carrying out this method.

In the diagram of figure 1, the thickness of the separation room, that is to say the distance between the

inner and outer cylindrical walls of this room, which is transversal to the flow direction of blood to be separated, corresponds to the y co-ordinate, whereas the x co-ordonate corresponds to the flow direction of this blood between upstream and downstream ends of this separation room. This room has preferably a cylindrical shape and is rotated around its central axis so that the blood flow through this room is simultaneously submitted to a centrifugal force field. Due to the higher density of the red blood cells (RBC) they deposit at first against the external wall of the upstream section of the separating room where they are col- lected.

However, the x dimension of the separation room is set by the length of the platelet sedimentation path which is 15 times longer than that of red blood cells. Since the flow in the separation room is substantially laminar, and since in that case the outer wall is actually formed by the red blood cell flowing, the speed profil is substantially triangular, so that the platelet sedimentation path has the curve profil illustrated in figure 1.

It may be observed that"above"or inside the curve of platelet sedimentation path in figure 1 (with respect to the center of rotation when the separation room has a circular shape), in the flow part situated in the smallest radius of the separation room, there is only platelet-poor plasma PPP, whereas"under"or outside this curve, in the flow part situated in the larger radius of this room, there is only platelet-rich plasma PRP to be concentrated into platelet concentrate (PC), which is the blood component to be recove- red in this case.

If PPP is collected as it is formed, for instance by connecting the inner side of a circular separation room to a suction source, or by feeding the whole blood under pressu-

re, as it will be explained hereunder, three effects result from this PPP collection: - The boundary line between PRP and PPP moves towards the inner side of the circular separating room, as it may be observed on the diagram of figure 2. This first effect could be detrimental if the suction flow rate were not well controlled, so that an unwanted part of PRP could be collected simultaneously with PPP.

- Due to the suction of PPP or its driving out of the separation room, the overall flow rate decreases so that the slope of the platelet sedimentation path sharply increases downstream from the suction, reducing substantially the sedimentation time as well as the length of sedimentation path.

- Since following the suction of PPP or its driving out of the separation room, the overall flow rate decreases, the separation between PPP and PRP is made easier.

The PPP has to be sucked or driven out at the very beginning of the separation between PPP and PRP, where the slope of the platelet sedimentation path is the sharpest, to be effective. If the suction source is connected to the inner side of the separation room by a plurality of ope- nings, as illustrated in the diagram of figure 2, the length of the separation room may dramatically decrease from 2 meters to 200 mm.

According to the diagrams of figures 1 and 2, the platelet sedimentation path in a whole blood flowing into a cylindrical room rotating around its central axis corres- ponds to x and y speeds at once. If one takes into conside- ration the path of the smallest platelet starting at the innermost radius of the separation room, that is to say the less favorable sedimentation condition, as illustrated in figure 2, this path forms also the boundary line which

separates PPP and PRP. Therefore, if the length of the separation room is at least as long as that of. the above boundary line according to the x co-ordinate, the plasma collected at an outlet opening of the separation room is substantially free from platelets.

It may be observed from the above statement that the separation method according to the invention is followed by a very important reduction of sedimentation time and by that of the length of the sedimentation path and therefore by a reduction of the overall dimensions of the separation mem- ber. Such a smaller separation member is particularly adap- ted to be produced as a disposable member and gives at the same time the posssibility to reduce the dimensions of cen- trifugal apparatus. Moreover this method is followed by a substantial improvement of the platelet collection efficen- cy.

The separation device for carrying out this separation method, depicted in Figures 3 and 4 comprises a separation room 1 which is circularly shaped around a central axis A of a centrifugal bowl B. This room 1 has a generally tubular shape and a generally narrow rectangular cross-sectional form, the radial thickness of which is comprised between 2 and 5 mm. The long sides of this separation room 1 are parallel to the central axis A, so that a centrifugal force field results from the rotation of the separation room 1 around the central axis A.

The upstream end of the separation room 1 with respect to the blood flow direction, has a feeding tube 4 connecting a supply S of whole blood (WB) to a distributing space 3 which extends vertically all over the axial dimension of the separation room 1 and opens into said room through a distri- buting slit 3b intended to generate a pressure drop able to uniformly distribute the whole blood all over the axial

dimension of this separation room 1. The downstream end of this room has an outlet opening 5 connected by a discharge tube 6 into a platelet concentrate (PC) collector 7. In this case, the supply S is preferably formed by a peristaltic pump so that the pressure in the separation room 1 is higher than the atmospheric pressure. Another outlet opening 8 is at an end of a first separating section la of the room 1, in which substantially all deposited RBC are gathered along the outer wall of the room 1. This other outlet opening 8 is situated between the inlet opening 3 and the downstream end outlet opening 5 and is provided at an end of a discharge tube 9 adjacent to the outer wall of the separation room 1 with respect to the central axis A. This discharge tube 9 is connected to a collector container 10 which is at the atmos- pheric pressure so that since the pressure inside the sepa- ration room 1 is higher than the atmospheric pressure, the RBC gathered along the outer wall of the separation room 1 are driven out through the outlet opening 8.

A collector channel 12 is connected on the one hand, to a collector container 17 through a discharge tube 13, and on the other hand to the first separating section of the sepa- ration room 1 through a plurality of openings 11 provided through the inner wall of said first separating section of the separation room 1 with respect to the central axis A.

All these openings 11 are connected to the collector channel 12, through separate divider elements 15 for evenly distributing the relative depressure between the collector channel 12 and the separation room 1.

Preferably, as depicted in figure 4, the openings 11 have the form of elongated slits extending substantially on the overall height of the separation room 1 and the divider elements 15 have a tubular form also extending substantially all over the height of the separation room 1. Similarly, the

outlet openings 5 extend also in a parallel direction to the central axis, on the overall height of the separation room 1.

Downstream to the first separating section of the room 1, the outer wall of this room 1 comprises leucocyte trap- ping recesses 14 arranged in series which cause the leucocy- te to separate from the platelet concentrate (PC) which is collected through the discharge tube 6 into the PC collector 7.

Owing to the above-disclosed structure of the separa- ting device according to the invention, the separtion room 1 and the connecting tubes 4,6, 9,13 are situated between two members B1,-B2 fitted one into the other for forming the separating device and the walls of this separation room 1 and that of this connecting tubes 4,6, 9,13 are partly formed on each of these two members. Accordingly, each of these members B1, B2 may be directly obtained by an injec- tion molding process. The external member B1 is a substan- tially cylindrical cup in which a substantially cylindrical internal member B2 is fitted. These members B1, B2 are welded together. The connecting tubes 4,6, 9,13 are open channels formed in the bottom surface of the internal member B2. These channels are laterally closed by the bottom wall of the external cup B1 when the members B1, B2 are welded together. The vertical slits 11 and the divider elements 15, which are formed by vertical cylindrical ducts, are also directly obtained from the injection molding of the internal member B2. Typically, the separation room has a diameter between 50 and 120 mm.

According to an example of the separating method of the invention, the WB flow rate was 60 ml/min which was separa- ted into 18 ml/min of PPP, 34 ml/min of RBC and 8 ml of PC.

In this example the suction of PPP was distributed between

27 slits parallel to the central axis A of the centrifugal bowl B.

According to the specific case, the WB flow rate may be increased up to around 300 ml/min and the ratio between the flow rates of PPP, RBC and PC may be adapted in relation with the required PC concentration.

The embodiment of figure 5 differs from that of figures 3 and 4 principally by the component to be collected.

Instead of collecting platelets this embodiment relates to a plasmapheresis method. Indeed, taking into account the en- hancing platelet recovery efficency of the separation method according to this invention, the collected plasma is sub- stantially free from platelets, so that this process would be also well suited for extraction of substantially free platelet plasma from whole blood. In this embodiment, the separation room la comprises only one inlet opening 3a connected to a supply S of whole blood (WB) by a feeding tube 4a and one outlet opening 8a provided at the end of a discharge tube 9a. A plurality of openings lla are provided through the inner wall of the separation room la with res- pect to the central axis A. All these openings lla are con- nected to a same collector channel 12a, through separate divider elements 15a for evenly distributing the depressure of the collector channel 12a which is connected to a suction source 10a through a discharge tube 13a. Preferably, a fil- tering member 16 is placed through the inlet end of this discharge tube 13a in order to prevent any possible platelet to be collected with the plasma.