JP2005296675A - Blood component separating apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a blood product of high quality which has a high extraction ratio of white blood cells in a short processing time. <P>SOLUTION: A blood component separating apparatus 1B has a centrifugal ball 4, its rotary drive 5, a first line 2 which introduces a blood and a blood plasma into the centrifugal ball 4, a second line 3 which collects centrifuged blood components, a buffy coat bag 25, a third line 8 which transfers a buffy coat, a fourth line 10 which provides the blood, optical sensors 61 and 62, a control means, and a pump 91 which is placed on the first line 2. In this apparatus 1B, the blood transferred from the fourth line 10 is centrifuged in the centrifugal ball 4. An obtained buffy coat is stored once in the buffy coat bag 25. After that, this buffy coat is returned to a blood storing space 46. The blood plasma is provided from below during centrifuging and thrombocyte is made to float up th the surface. This thrombocyte is collected in a thrombocyte bag 17 through the second line 3. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a blood component separation device for separating a predetermined blood component from blood.

  At the time of blood collection, for the purpose of effective use of blood and reduction of burden on blood donors, the blood sample is separated into each blood component by centrifugation, etc., and only the components necessary for the transfuser are collected. Ingredients are collected to return the ingredients to the blood donor.

  In such a component blood collection, when obtaining a platelet preparation, blood collected from a blood donor is introduced into a blood component separation circuit, and a centrifuge called a centrifuge bowl installed in the blood component separation circuit is used for plasma, white blood cells, The platelets and red blood cells are separated into four components, and the platelets are collected in a container to obtain a platelet preparation, and the remaining plasma, white blood cells and red blood cells are returned to the blood donor. In order to secure the target platelet count, a series of blood processing steps including the blood collection, the centrifugation of the collected blood, the collection of platelets, and the return of blood are performed a plurality of times.

  However, in this method, since the specific gravity of white blood cells and platelets is a slight difference, these interfaces are not clear and are recognized as an integral buffy coat layer containing white blood cells and platelets. As a result, there is a problem that the probability of infection such as hepatitis, AIDS, and GVHD increases when the platelet preparation is used.

  Therefore, a method (surge method) has been proposed in which the plasma obtained before the bottom of the centrifuge bowl is supplied to float the platelets and the platelets are collected (surge method). Since the amount of buffy coat layer in the centrifuge bowl is small and the plasma supply rate is relatively high (200 ml / min or more), the leukocyte removal rate in platelets is also low. The problem is not solved.

  An object of the present invention is to provide a blood component separation device having a high yield of platelets obtained by centrifugation or a high removal rate of leukocytes in the platelets.

Such an object is achieved by the present inventions (1) to (11) below.
(1) A blood component separation apparatus for separating blood into a plurality of blood components and transferring the separated blood components,
A rotatable rotor having a blood storage space therein, and an inlet and an outlet communicating with the blood storage space, and blood introduced from the inlet by rotation of the rotor is a plurality of blood in the blood storage space A centrifuge to centrifuge the components;
A first line connected to the inlet;
A second line connected to the outlet;
A buffy coat bag for storing the buffy coat;
One end is connected to the buffy coat bag, the other end is connected to the first line and / or the second line, and the third line and the first line and the second line, A fourth line for supplying blood;
A platelet bag installed or connected to the second line and storing platelets;
The blood is introduced into the blood storage space through the fourth line and the first line and the rotor is rotated, and the blood is centrifuged to separate into a plurality of blood components, and then obtained. After performing at least one buffy coat collecting operation for transferring the buffy coat to the buffy coat bag through the third line,
The buffy coat in the buffy coat bag is supplied to the first line or the second line via the third line, and introduced into the blood storage space together with the blood fed from the fourth line. Perform buffy coat inflow operation,
Thereafter, the blood component separation device is operated so as to perform a platelet collecting operation for collecting the platelets obtained by centrifugation through the second line into the platelet bag.

  (2) The third line has one end connected to the buffy coat bag, the other end connected to the first line, one end connected to the buffy coat bag, and the other end The blood component separation device according to (1), further comprising a second tube connected to the second line.

(3) having a pump installed between a connection portion of the first line with the fourth line and a connection portion of the third line with the first tube;
The blood component separation device according to (2), wherein the buffy coat bag is provided so that a connection portion with the second tube of the third line faces downward.

  (4) The blood component separation device according to (2), further including a pump installed between the connection portion of the third line with the first tube in the first line and the inlet.

  (5) Between the connection portion of the first line with the fourth line and the connection portion of the third line with the first tube and in the middle of the first tube of the third line. The blood component separation device according to the above (2), which has a pump installed therein.

  (6) The blood component separation device according to any one of (1) to (5), further comprising a plasma bag that is installed or connected to the second line and stores plasma.

  (7) After the buffy coat inflow operation, the cleaning liquid is introduced into the buffy coat bag, the buffy coat bag is cleaned, and then the cleaning liquid used for the cleaning is returned to the blood storage space. The blood component separation device according to any one of (1) to (6), which operates.

  (8) After the buffy coat inflow operation, plasma obtained by centrifugation is introduced into the buffy coat bag, the buffy coat bag is washed, and then the plasma subjected to the washing is stored in the blood reservoir The blood component separation device according to any one of (1) to (6), wherein the blood component operation is performed so as to perform a washing operation for returning the space.

(9) After the buffy coat inflow operation, plasma obtained by centrifugation is introduced into the buffy coat bag, the buffy coat bag is washed, and then the plasma subjected to the washing is stored in the blood reservoir A blood component separation device that performs a washing operation to return to space,
The washing operation introduces plasma obtained by centrifugation to the buffy coat bag through the second tube of the second line and the third line to wash the buffy coat bag, Then, the plasma subjected to the washing is returned to the blood storage space via the first tube and the first line of the third line, and the plasma is subjected to any one of the above (2) to (6) The blood component separation device described.

  (10) In the platelet collecting operation, plasma is supplied at a plasma supply rate of 10 to 90 ml / min from below the blood storage space under the rotation of the rotor to float the platelets, and the platelets flowing out from the outlet are collected. The blood component separation device according to any one of the above (1) to (9).

  (11) The blood component separation device according to any one of (1) to (10), wherein the fourth line includes a blood reservoir or a puncture needle.

  According to the blood component separation device of the present invention, when separating into a plurality of blood components and transferring the blood components, it becomes possible to perform separation and transfer with higher accuracy. In particular, when applied to component blood collection, recovery of platelets A high-quality blood product having a high rate and a very high removal rate of leukocytes (particularly lymphocytes) in the collected platelets can be obtained. As a result, infection such as hepatitis, AIDS, and GVHD can be prevented with higher probability, and safety is high.

  In the present invention, since the platelets are collected at a time, the entire processing time can be shortened. In particular, when the third line includes the first tube and the second tube, the entire processing time can be further shortened.

  Further, in the platelet collection operation, when a method of supplying plasma from below the blood storage space to float and collect the platelets is employed, particularly when the plasma supply rate is 10 to 90 ml / min, the platelet recovery rate Moreover, the leukocyte removal rate is further improved.

  Further, when the buffy coat bag for storing the buffy coat is washed and the liquid used for the washing is returned to the blood storage space, platelets do not remain and the platelet collection rate is further improved.

  Hereinafter, the blood component separation device of the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.

  FIG. 1 is a plan view showing a first embodiment of the blood component separation apparatus of the present invention, and FIG. 2 is a block diagram showing a control system of the blood component separation apparatus shown in FIG. As shown in these drawings, the blood component separation device 1A includes a centrifugal bowl (centrifugal separator) 4, a rotation drive device 5 thereof, and a first line 2 for selectively introducing blood and plasma into the centrifugal bowl 4. (Blood or plasma introduction line), a second line 3 (blood component collection line) for collecting blood components separated in the centrifugal bowl 4, a buffy coat bag 25 that is a container for storing a buffy coat, The third line 8 for introducing the buffy coat in the buffy coat bag 25 into the centrifuge bowl 4, the optical sensors 61 and 62, the control means 7, and the fourth line having the blood reservoir 106 (supposing a blood donor) A blood removal / return line 10, and a pump 91 installed in the first line 2.

  As shown in FIG. 1, the fourth line 10 mainly includes a tube 101, a tube 103 connected to the middle of the tube 101 via a to-shaped branch connector 102, and the tips of the tubes 101 and 103. The blood bags 104 and 105 are connected to each other. Both blood bags 104 and 105 constitute a blood reservoir 106.

  The base end of the tube 101 is connected to one end of the tubes 13 and 20 via the T-shaped branch connector 12. In the middle of the tube 101, a valve 83 is installed as a channel opening / closing means that can block and release the internal channel of the tube 101.

  The first line 2 includes a tube 13 and a branch connector 12 connected to one end thereof. The other end of the tube 13 is connected to the inlet 43 of the centrifuge bowl 4, and a liquid feeding pump 91 made of, for example, a roller pump is installed in the middle of the tube 13.

  As shown in FIG. 3, the centrifuge bowl 4 is a tube 41 that extends in the vertical direction with an inlet 43 formed at the upper end, rotates around the tube 41, and is liquid-tightly sealed with respect to the upper portion 45. The rotor 42 is configured. An annular blood storage space 46 is formed inside the rotor 42 along the inner surface of the rotor peripheral wall. The blood storage space 46 has a shape (tapered shape) whose inner and outer diameters gradually decrease from the lower part to the upper part in FIG. The lower part of the blood storage space 46 communicates with the lower end opening of the tubular body 41 via a substantially disc-shaped channel 47 formed along the bottom of the rotor 42, and the upper part of the blood storage space 46 is connected via the channel 48. It communicates with the outlet 44. In the rotor 42, the volume of the blood storage space 46 is, for example, about 100 to 350 ml.

  Such a rotor 42 is rotated under predetermined centrifugal conditions (rotation speed and rotation time) set in advance by the rotary drive device 5. Under this centrifugal condition, the blood separation pattern (for example, the number of blood components to be separated) in the rotor 42 can be set. In this embodiment, as shown in FIG. 3, the centrifugal conditions are set so that the blood is separated from the inner layer into the plasma layer 31, the buffy coat layer 32, and the red blood cell layer 33 in the blood storage space 46.

  As shown in FIG. 3, the rotary drive device 5 includes a housing 51 that houses the centrifugal bowl 4, a leg portion 52, a motor 53 that is a drive source, and a disk-shaped fixing base 55 that holds the centrifugal bowl 4. It is configured.

  The housing 51 is placed and fixed on the upper portion of the leg portion 52. In addition, a motor 53 is fixed to the lower surface of the housing 51 via a spacer 57 with a bolt 56. A fixed base 55 is fitted on the tip of the rotary shaft 54 of the motor 53 so as to rotate coaxially and integrally with the rotary shaft 54, and the bottom of the rotor 42 is fitted on the top of the fixed base 55. A recess 551 is formed. The upper part 45 of the centrifuge bowl 4 is fixed to the housing 51 by a fixing member (not shown).

  In such a rotation driving device 5, when the motor 53 is driven, the fixed base 55 and the rotor 42 fixed thereto rotate at, for example, a rotation speed of 3000 to 6000 rpm.

  On the inner wall of the housing 51, an optical sensor 61 that optically detects the interface of the separated blood components in the rotor 42, that is, the position of the interface B between the buffy coat layer 32 and the red blood cell (concentrated red blood cell) layer 33, The mounting member 58 is installed and fixed. As the optical sensor 61, a line sensor capable of scanning in the vertical direction along the outer peripheral surface of the rotor 42 is used. That is, a light emitting element such as an LED and a light receiving element such as a photodiode are arranged in a line, and the light reflected from the blood component of the light emitted from the light emitting element is received by the light receiving element, and the amount of received light is determined. It is configured to perform photoelectric conversion. Since the intensity of the reflected light is different between the separated buffy coat layer 32 and the red blood cell layer 33, the position corresponding to the light receiving element in which the amount of received light, that is, the output voltage is changed, is detected as the position of the interface B.

  As shown in FIG. 1, one end of the tube 14 is connected to the outlet 44 of the centrifuge bowl 4, and the other end of the tube 14 is connected to one end of the tubes 16 and 18 via a T-shaped branch connector 15. Has been.

The other end of the tube 16 is connected to the platelet bag 17, and a valve 85 that opens and closes the flow path in the tube 16 is installed in the middle of the tube 16.
The other end of the tube 18 is connected to a bubble removal chamber 19, and a valve 86 that opens and closes the flow path in the tube 18 is installed in the middle of the tube 18.

  The other end of the tube 20, one end of which is connected to the branch connector 12, is connected to a bubble removal chamber 19. A valve 84 that opens and closes the flow path in the tube 20 is installed in the middle of the tube 20. .

  The air storage bag 22 is a bag for discharging air from the plasma bag 21 after a series of processes and storing the air. Therefore, the plasma bag 21 and the air storage bag 22 are connected to each other by a tube 23. They communicate with each other. One end of a tube 24 is connected to the plasma bag 21, and the other end of the tube 24 is connected to a bubble removal chamber 19.

  In such a configuration, the tube 14, 16, 18, 20, 23, 24, the branch connector 15, the chamber 19 and the bags 17, 21, 22 constitute the second line 3. Among these, the tube 18, the chamber 19, the tubes 23 and 24, and the bags 21 and 22 constitute a plasma collection branch line for collecting plasma, and the tubes 14 and 16 and the platelet bag 17 are for collecting platelets. A branch line for collecting platelets is constructed.

  Although not shown, the plasma bag 21 may be set in a device (bag swing device) that can selectively orient the connection side end of the tube 24 upward or downward.

  A branch connector 28 is installed in the vicinity of the outlet 44 of the tube 14, and one end of the tube 26 is connected to the branch connector 28. The other end of the tube 26 is connected to the buffy coat bag 25, and a valve 87 that opens and closes the flow path in the tube 26 is installed in the middle of the tube 26. The tube 26 and the branch connector 28 constitute a third line 8.

A plurality of such buffy coat bags 25 may be provided, and the connection pattern is not particularly limited. The volume of the buffy coat bag 25 is not particularly limited, but usually the total volume is preferably about 100 to 800 ml, more preferably about 400 to 500 ml.
Although not shown, the buffy coat bag 25 may be set in the same bag swinging device as described above.

  Further, an optical sensor 62 that can detect the concentration of platelets in blood components flowing in the tube 14 is installed in the middle of the tube 14. The optical sensor 62 includes a light projecting unit (light source) 63 and a light receiving unit (photodiode) 64 that are arranged to face each other via the tube 14. Light (for example, laser light) emitted from the light projecting unit 63 passes through the tube 14 and is received by the light receiving unit 64 and converted into an electrical signal corresponding to the amount of received light, but the blood component flowing in the tube 14 The transmittance changes according to the concentration of platelets therein, and the amount of light received by the light receiving unit 64 varies. Therefore, this variation can be detected as a change in the output voltage from the light receiving unit 64.

  Each of the valves 83 to 87 is operated by a drive source such as a solenoid, an electric motor, or a cylinder (hydraulic pressure or air pressure), and the drive source is operated based on a signal from the control means 7 described later. In the present invention, the channel opening / closing means is not limited to the valve (cock), and may be a clamp that can close the inner cavity of the flexible tube, for example.

  Each of the bags 17, 21, 22, 25, 104, and 105 is made of a resin-made flexible sheet material, and its peripheral portion is fused (heat fusion, high frequency fusion, etc.) or bonded. It is a bag.

  For example, soft polyvinyl chloride is preferably used as a constituent material of the sheet material constituting each of the bags 17, 21, 22, 25, 104, and 105. As the plasticizer in the soft polyvinyl chloride, for example, di (ethylhexyl) phthalate (DEHP), di- (n-decyl) phthalate (DnDP) or the like is used. In addition, it is preferable that content of such a plasticizer shall be about 30-70 weight part with respect to 100 weight part of polyvinyl chloride.

  Further, as another constituent material of the sheet material of each bag 17, 21, 22, 25, 104, 105, polyolefin, that is, a polymer obtained by polymerizing or copolymerizing olefins or diolefins such as ethylene, propylene, butadiene, isoprene, etc. For example, polyethylene, polypropylene, ethylene-vinyl acetate copolymer (EVA), polymer blends of EVA and various thermoplastic elastomers, or any combination thereof. Furthermore, polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT), poly-1,4-cyclohexanedimethyl terephthalate (PCHT), and polyvinylidene chloride can also be used.

  In addition, the sheet material constituting the platelet bag 17 is preferably one having excellent gas permeability in order to improve platelet storage stability. For this purpose, for example, the above-mentioned polyolefin or DnDP plasticized polyvinyl chloride is used as the sheet material. In addition, it is preferable that the thickness of the sheet material is relatively thin (for example, about 0.1 to 0.5 mm, particularly about 0.1 to 0.3 mm).

Blood is stored in advance in at least one of the blood bags 104 and 105. For example, an anticoagulant such as an ACD-A solution, a CPD solution, a CPD-A1 solution, or a heparin sodium solution is preferably added to the blood. Note that the number of blood bags installed in the blood reservoir 106 may be one or three or more, and the connection method and connection pattern thereof are arbitrary. For example, one or two or more blood bags can be aseptically connected and exchanged using a tube connecting device described in Japanese Utility Model Laid-Open No. 6-26877.
Moreover, although the platelet bag 17 may be in an empty state, for example, a platelet preservation solution such as physiological saline, GAC, PAS, or PSM-1 may be placed in advance.

The constituent materials of the tubes 101, 103, 13, 14, 16, 18, 20, 23, 24, 26, 27 include, for example, polyvinyl chloride, polyethylene, polypropylene, polyesters such as PET and PBT, and ethylene-vinyl acetate. Examples thereof include thermoplastic elastomers such as copolymers, polyurethanes, polyester elastomers, and styrene-butadiene-styrene copolymers, among which polyvinyl chloride is particularly preferable. If each tube is made of polyvinyl chloride, sufficient flexibility and softness can be obtained, so that it is easy to handle and is suitable for clogging with a clamp or the like.
Further, the constituent materials of the branch connectors 102, 12, 15, 28, and 29 can be the same as the constituent materials of the tube.

  As shown in FIG. 2, the blood component separation apparatus 1A has a control means 7 composed of, for example, a microcomputer. The control means 7 includes the pump 91, valves 83 to 87, optical sensors 61 and 62, and The rotary drive devices 5 are electrically connected to each other.

  A detection signal (interface position detection information) from the optical sensor 61 and a detection signal (platelet concentration information) from the optical sensor 62 are input to the control means 7 as needed. The control means 7 controls the rotation / stop, rotation direction (forward / reverse rotation) and rotation speed of the pump 91 based on the detection signals from the optical sensors 61 and 62, and the valves 83 to 87 as necessary. The opening / closing operation and the operation of the rotation driving device 5 are controlled.

  The blood component separation apparatus 1A using the centrifugal bowl 4 as described above has an advantage that the collected platelets are pelleted (to be agglomerated) compared to the method of centrifuging blood in a bag.

  Next, a preferred embodiment of a platelet collection method using the blood component separation device 1A shown in FIG. 1 will be described. The operating states of the valves 83 to 87, the rotor 42, and the pump 91 in the following steps are shown in Table 1 below, and will be described with reference to Table 1.

  [1a] Each of the blood bags 104 and 105 is filled with, for example, 400 ml of collected blood, the tube 103 is closed with a clamp, and the pump 91 is operated with the valve opening / closing pattern (1) in Table 1 (Forward). Thereby, the blood in the blood bag 104 is transferred through the tubes 101 and 13 and introduced into the rotor 42 from the inlet 43 of the centrifuge bowl 4 through the tube body 41. The rotation speed of the pump 91 is set so that the blood discharge amount (blood supply speed) is, for example, about 30 to 80 ml / min.

  [2a] Further, simultaneously with the blood transfer in the step [1a], the rotation driving device 5 is operated to rotate the rotor 42 preferably at 3000 to 6000 rpm (for example, 4800 rpm). The blood flowing out from the lower end opening of the tube body 41 flows radially toward the outer circumferential direction through the flow path 47 by the centrifugal force generated by the rotation of the rotor 42, and is collected in the blood storage space 46. 31, the buffy coat layer 32 and the red blood cell layer 33 are separated.

  [3a] When the plasma layer 31 reaches the upper part of the blood storage space 46 while continuing the steps [1a] and [2a], the valve opening / closing pattern is set to (2). Thereby, the plasma in the rotor 42 overflows from the outlet 44 and is collected in the plasma bag 21 via the tubes 14, 18, the chamber 19, and the tube 24.

  [4a] As the plasma is discharged from the rotor 42, the interface B between the buffy coat layer 32 and the red blood cell layer 33 also gradually rises. This interface B is detected at any time by the optical sensor 61. When it is detected that the interface B reaches a predetermined level, that is, a level at which the buffy coat starts to flow out from the outlet 44, the control means 7 Based on the detection signal (interface position detection information), the valve opening / closing pattern is controlled to be (3). Thereby, the buffy coat that has flowed out from the outlet 44 is transferred to the buffy coat bag 25 through the tubes 14 and 26 and collected thereafter.

  [5a] When the optical sensor 61 detects that the interface B reaches a predetermined level, that is, a level at which almost all the buffy coat is discharged from the blood storage space 46, the control means 7 detects the detection signal ( Based on the interface position detection information), the rotation driving device 5 is stopped, the valve opening / closing pattern is set to (4), and the pump 91 is controlled to rotate in the reverse direction. Thereby, the red blood cells remaining in the centrifuge bowl 4 are returned to the blood bag 104 via the tube body 41 and the tubes 13 and 101.

  [6a] The valve opening / closing pattern is set to (5), the pump 91 is operated (forward rotation), and all or part of the plasma in the plasma bag 21 is transferred to the rotor 42 via the tube 24, chamber 19, tubes 20, 13. Put in.

  [7a] Subsequently, the valve opening / closing pattern is set to (6), the pump 91 is rotated in the reverse direction, and the plasma in the centrifuge bowl 4 transferred from the plasma bag 21 is transferred to the blood via the tube body 41 and the tubes 13 and 101. Blood is returned into the bag 104.

  [8a] The middle of the tube 101 between the branch connector 102 and the blood bag 104 is sealed by, for example, fusion, and this sealing portion is cut and separated. Thereby, the blood bag 104 containing platelet-poor blood for returning blood is obtained. Platelet-poor blood in the blood bag 104 is returned to the blood donor as necessary.

  When the number of blood bags to be processed is n (n = an integer greater than or equal to 3), the above steps [1a] to [8a] are repeated for up to n−1 blood bags, The following steps are performed on the blood bag.

  [9a] The rotary drive device 5 is operated to rotate the rotor 42 at, for example, 3000 to 6000 rpm, and the valve opening / closing pattern is (7) with the connection side end of the tube 26 of the buffy coat bag 25 facing downward. Then, the pump 91 is reversely rotated. Thereby, the buffy coat stored in the buffy coat bag 25 is returned to the blood storage space 46 through the tubes 26, 14, the outlet 44, and the flow path 48.

  [10a] The blockage of the tube 103 by the clamp is released, the valve opening / closing pattern is set to (8), and the pump 91 is operated (forward rotation) under the same conditions as in the step [1a]. Thereby, the blood in the blood bag 105 is transferred through the tubes 103, 101 and 13, introduced into the rotor 42 through the tube body 41 from the inlet 43 of the centrifugal bowl 4, and the blood is the inner layer in the blood storage space 46. The plasma layer 31, the buffy coat layer 32, and the red blood cell layer 33 are further separated.

  In this case, the buffy coat layer 32 is composed of a buffy coat in an amount obtained from the total blood in a plurality of blood bags (blood bags 104 and 105 in the illustrated configuration) corresponding to a plurality of blood collections. The layer thickness is increased, and in the surge process described later, the floating and concentration of platelets are performed more clearly, and the yield of platelets and the removal rate of leukocytes in collected platelets are improved.

  [11a] When plasma flows out from the outlet 44, first, the valve opening / closing pattern is set to (9). As a result, the plasma flowing out from the outlet 44 is introduced into the buffy coat bag 25 through the tubes 14 and 26, and the flow paths of the tubes 14 and 26 and the inside of the buffy coat bag 25 are washed. At this time, it is preferable to swing the buffy coat bag 25 because the cleaning effect inside thereof is increased.

  [12a] With the connection side end of the tube 26 of the buffy coat bag 25 facing downward, the valve opening / closing pattern is (10) and the pump 91 is rotated in reverse. As a result, plasma (cleaning liquid) used for cleaning the inside of the buffy coat bag 25 and the like is returned to the blood storage space 46 via the tubes 26, 14, the outlet 44, and the flow path 48. In addition, the buffy coat bag 25 may be placed at a high place, a predetermined air vent may be provided as necessary, and the cleaning liquid in the buffy coat bag 25 may be transferred to the blood storage space 46 by a drop, or the buffy coat bag 25 may be The cleaning liquid may be discharged and transferred by being sandwiched and pressed by a pair of pressure plates or the like.

  By washing the inside of the buffy coat bag 25 and the like and collecting the washing liquid in the blood storage space 46, the platelets do not remain in the buffy coat bag 25 and the like, and the yield of platelets is improved.

  [13a] The valve opening / closing pattern is (11), and the pump 91 is operated (forward rotation). Thereby, the plasma in the plasma bag 21 is supplied into the rotor 42 through the tube 24, the chamber 19, the tubes 20, 13 and the tube body 41, and further flows through the tubes 14 and 16, and the surge circuit is primed with plasma. The

  [14a] Next, the valve opening / closing pattern is (12). As a result, the plasma in the rotor 42 flows out from the outlet 44 and is collected in the plasma bag 21 through the tubes 14, 18, the chamber 19, and the tube 24.

  [15a] By the optical sensor 61, the interface B has a predetermined surge start level, that is, the ratio of the volume of the red blood cell layer 33 existing in the blood storage space 46 to the volume of the blood storage space 46 is preferably 70 to 96%, more preferably 85. When it is detected that the level when it reaches ˜94% is reached, the control means 7 controls the valve opening / closing pattern to be (13) based on the detection signal (interface position detection information). Thereby, the plasma in the plasma bag 21 is supplied into the rotor 42 via the tube 24, the chamber 19, the tubes 20 and 13, and the tube body 41. The plasma flowing out from the lower end opening of the tube body 41 flows radially through the flow path 47 by the centrifugal force generated by the rotation of the rotor 42, and rises in the blood storage space 46 through the lower part of the blood storage space 46. As a result, the platelets in the buffy coat layer 32 float against the centrifugal force (float up), flow out of the outlet 44 through the flow path 48, and are collected in the platelet bag 17 through the tubes 14 and 16. (Surge process). The outflow of platelets is detected by the increase in platelet concentration by the optical sensor 62.

  In this surge process, the control means 7 controls the rotational speed (plasma discharge amount) of the pump 91, so that the plasma supply speed into the rotor 42 is preferably 10 to 90 ml / min, more preferably 10 to 70 ml. Set to / min. If the plasma supply rate is less than 10 ml / min, it takes a long time to collect platelets. If it exceeds 90 ml / min, the levitated amount of leukocytes increases together with the platelets, and the removal rate of leukocytes in the collected platelets decreases. It is.

  Further, during the collection of platelets, the plasma supply rate may be appropriately changed within the range of 10 to 90 ml / min. For example, there is a method in which plasma is first supplied at a predetermined rate and then supplied at a lower rate at least once. In such a case, the maximum plasma supply rate is preferably 25 to 90 ml / min, particularly 30 to 70 ml / min. Such a change in the plasma supply rate can be performed based on, for example, a timer built in the control unit 7 or according to platelet concentration information detected by the optical sensor 62.

  [16a] When the platelet concentration detected by the optical sensor 62 is equal to or lower than a preset reference value, it is considered that the collection of the platelets into the platelet bag 17 is completed, and the control means 7 detects the detection signal (platelet concentration). On the basis of the information), the rotation drive device 5 is stopped, the valve opening / closing pattern is set to (14), and the pump 91 is controlled to reversely rotate. As a result, red blood cells, white blood cells and plasma remaining in the centrifuge bowl 4 are returned to the blood bag 105 via the tube body 41 and the tubes 13 and 101.

  [17a] The valve opening / closing pattern is set to (15), the pump 91 is operated (forward rotation), and the plasma remaining in the plasma bag 21 is put into the rotor 42 via the tube 24, the chamber 19, and the tubes 20, 13. .

  [18a] Subsequently, the valve opening / closing pattern is set to (16), the pump 91 is rotated in the reverse direction, and the plasma in the centrifuge bowl 4 transferred from the plasma bag 21 passes through the tube body 41 and the tubes 13 and 101 to the blood. Blood is returned into the bag 105.

  [19a] The middle of the tube 103 is sealed by, for example, fusion, and the sealing portion is further cut and separated. Thereby, a blood bag 105 containing platelet-poor blood for returning blood is obtained. Platelet-poor blood in the blood bag 105 is returned to the blood donor as necessary.

  [20a] The tube 16 near the platelet bag 17 is sealed by, for example, fusion, and the sealed portion is cut and separated to obtain the platelet bag 17 containing the platelet preparation.

  As described above, in the present invention, a buffy coat of an amount obtained from the total blood in a plurality of blood bags (blood bags 104 and 105 in the illustrated configuration) is collected, and a surge process is performed on this at once. The thickness of the buffy coat layer 32 in the blood storage space 46 at the time of surge is increased, so that the floating and concentration of platelets from the buffy coat layer 32 are more clearly performed, and the yield of platelets and the collected platelets are increased. The white blood cell removal rate is improved.

In particular, in the surge process, by setting the plasma supply rate to 10 to 90 ml / min, the floating of platelets is optimally adjusted, and thus a high-quality platelet preparation with an extremely high leukocyte removal rate can be obtained. In addition, since the interface of the separated blood component is detected by the optical sensor 61 and the timing of the start of plasma supply (end of blood supply) is controlled based on the detected interface, it is possible to control with higher accuracy together with automation. And the removal rate of leukocytes in the collected platelets are further improved. For this reason, when the platelet preparation is used, infections such as hepatitis, AIDS, and GVHD can be prevented with higher probability, and safety is high.
Further, since only one surge process is required, the entire processing time can be shortened.

  FIG. 4 is a plan view schematically showing the configuration of the second embodiment of the blood component separation device of the present invention. The blood component separation device 1B shown in the figure is the same as the blood component separation device 1A except that the configuration of the third line 8 is different.

  In the blood component separation device 1B, the buffy coat bag 25 is connected to one end of two tubes (second tubes) 26 and a tube (first tube) 27, respectively. Similarly to the above, the other end of the tube 26 is connected to the middle of the tube 14 via the branch connector 28, and the other end of the tube 27 is connected to the pump 91 and the inlet 43 of the tube 13 via the branch connector 29. Connected between. A valve 87 that opens and closes the flow path in the tube 26 is installed in the middle of the tube 26. The tubes 26 and 27 and the branch connectors 28 and 29 constitute a third line.

  The platelet collection method using such a blood component separation apparatus 1B is as follows, and is basically the same as the platelet collection method by the blood component separation apparatus 1A except for the step [12a].

  [1b] to [11b] The same steps as [1a] to [11a] are performed in a state where the tube 27 is closed with a clamp.

  [12b] Under the operation (forward rotation) of the pump 91, the valves 83 and 86 are opened and the other valves are closed. Further, the clogging of the tube 27 is released, the buffy coat bag 25 is placed at a high place, and the connection side end of the tube 26 is directed downward, and the cleaning liquid (plasma) in the buffy coat bag 25 is dropped by the drop. 27 to the first line 2. As a result, the cleaning liquid is mixed with the blood fed from the pump 91 in the branch connector 29 and transferred to the blood storage space 46 via the tube 13, the inlet 43, and the tube body 41.

  [13b] to [20b] Steps similar to [13a] to [20a] are performed in a state where the tube 27 is closed again with a clamp.

  In such a platelet collection method, the cleaning liquid (including platelets) in step [12b] can be returned without stopping the transfer of blood from the blood reservoir 106 into the rotor 42. There is an advantage that time can be shortened.

  FIG. 5 is a plan view schematically showing the configuration of the third embodiment of the blood component separation device of the present invention. The blood component separation device 1C shown in the figure is the same as the blood component separation device 1B except that the position of the pump 91 is different.

That is, in the blood component separation device 1 </ b> C, the pump 91 is installed between the branch connector 29 of the tube 13 and the inlet 43.
A platelet collection method using such a blood component separation device 1C is as follows. The operating states of the valves 83 to 87, the rotor 42, and the pump 91 in each step are shown in Table 2 below, and will be described with reference to Table 2.

  [1c] to [8c] The same steps as [1a] to [8a] are performed with the tube 27 closed with a clamp.

  [9c] The rotary drive device 5 is operated to rotate the rotor 42 at a predetermined number of revolutions, and the tube 103 is closed by the clamp, the valve opening / closing pattern is set to (8) in Table 2, and the pump 91 is Operate (forward rotation) under the same conditions as in step [1a]. Thereby, the blood in the blood bag 105 is transferred through the tubes 103, 101 and 13, introduced into the rotor 42 through the tube body 41 from the inlet 43 of the centrifugal bowl 4, and the blood is the inner layer in the blood storage space 46. The plasma layer 31, the buffy coat layer 32, and the red blood cell layer 33 are further separated.

  [10c] Simultaneously with the step [9c], the clogging of the tube 27 is released with the connection side end of the tube 26 of the buffy coat bag 25 facing downward. Thereby, the buffy coat stored in the buffy coat bag 25 is supplied to the first line 2 through the tube 27 by the operation of the pump 91, and is fed from the blood storage unit 106 side in the branch connector 29. The blood is mixed with the blood and then transferred to the blood storage space 46 through the tube 13, the inlet 43 and the tube body 41, and subjected to centrifugation. When almost the entire amount of the buffy coat is discharged from the buffy coat bag 25, the tube 27 is closed again with the clamp.

  In the blood storage space 46, the blood from the blood bag 105 and the buffy coat from the buffy coat bag 25 are mixed and centrifuged, and the separated buffy coat layer 32 corresponds to a plurality of blood collections. Since it is composed of a buffy coat in an amount obtained from the total blood in a plurality of blood bags (in the configuration shown, blood bags 104 and 105), the layer thickness is increased, and in the surge process, platelets float and concentrate. This is done more clearly and improves the yield of platelets and the removal rate of leukocytes in the collected platelets.

  [11c] When plasma flows out from the outlet 44, the valve opening / closing pattern is set to (9). As a result, the plasma flowing out from the outlet 44 is introduced into the buffy coat bag 25 through the tubes 14 and 26, and the flow paths of the tubes 14 and 26 and the inside of the buffy coat bag 25 are washed. At this time, it is preferable to swing the buffy coat bag 25 because the cleaning effect inside thereof is increased.

  [12c] With the connection side end of the tube 26 of the buffy coat bag 25 facing downward, the valve opening / closing pattern is (10), and the blockage of the tube 27 by the clamp is released again. Thereby, the plasma (washing liquid) used for washing the inside of the buffy coat bag 25 and the like is returned to the blood storage space 46 through the same route as in the step [10c].

  By washing the inside of the buffy coat bag 25 and the like and collecting the washing liquid in the blood storage space 46, the platelets do not remain in the buffy coat bag 25 and the like, and the yield of platelets is improved.

  [13c] to [20c] The same steps as [13a] to [20a] are performed in a state where the tube 27 is closed again with the clamp.

  In such a platelet collection method, the buffy coat is returned in step [10c] and the cleaning liquid (including platelets) is returned in step [12c] during the transfer of blood from blood reservoir 106 into rotor 42. In particular, since the buffy coat and the return of the cleaning liquid can be performed reliably and quickly by driving the pump 91, the entire processing time can be further shortened.

  FIG. 6 is a plan view schematically showing the configuration of the fourth embodiment of the blood component separation device of the present invention. The blood component separation apparatus 1D shown in the figure is the same as the blood component separation apparatus 1B except that a pump 92 is installed in the middle of the tube 27. As the pump 92, for example, a roller pump is used, and its driving is controlled by the control means 7 in FIG. The pump 92 only needs to be rotatable in only one direction. In this configuration, when the pump 92 is stopped, the flow path of the tube 27 is closed, but a valve (not shown) similar to the above may be provided in the middle of the tube 27.

  The platelet collection method using such a blood component separation device 1D is as follows. The operating states of the valves 83 to 87, the rotor 42, and the pumps 91 and 92 in each step are shown in Table 3 below, and will be described with reference to Table 3.

  [1d] to [8d] The same steps as [1a] to [8a] are performed with the pump 92 stopped.

  [9d] The rotary drive device 5 is operated to rotate the rotor 42 at a predetermined rotational speed, and the tube 103 is closed by the clamp. The valve opening / closing pattern is set to (8) in Table 3, and the pump 91 is Operate (forward rotation) under the same conditions as in step [1a]. Thereby, the blood in the blood bag 105 is transferred through the tubes 103, 101 and 13, introduced into the rotor 42 through the tube body 41 from the inlet 43 of the centrifugal bowl 4, and the blood is the inner layer in the blood storage space 46. The plasma layer 31, the buffy coat layer 32, and the red blood cell layer 33 are further separated.

  [10d] Simultaneously with the step [9d], the pump 92 is operated (forward rotation) with the connection side end of the tube 26 of the buffy coat bag 25 facing downward. Thereby, the buffy coat stored in the buffy coat bag 25 is supplied to the first line 2 via the tube 27, and the blood fed from the blood storage unit 106 side in the branch connector 29 The mixture is mixed, transferred to the blood storage space 46 through the tube 13, the inlet 43, and the tube body 41, and subjected to centrifugation. When almost the entire amount of the buffy coat is discharged from the buffy coat bag 25, the pump 92 is stopped.

  [11d] When plasma flows out from the outlet 44, first, the valve opening / closing pattern is set to (9). As a result, the plasma flowing out from the outlet 44 is introduced into the buffy coat bag 25 through the tubes 14 and 26, and the flow paths of the tubes 14 and 26 and the inside of the buffy coat bag 25 are washed. At this time, it is preferable to swing the buffy coat bag 25 because the cleaning effect inside thereof is increased.

  [12d] With the connection side end of the tube 26 of the buffy coat bag 25 facing downward, the valve opening / closing pattern is (10) and the pump 92 is operated (forward rotation). Thereby, the plasma (washing liquid) used for washing the inside of the buffy coat bag 25 and the like is returned to the blood storage space 46 through the same route as in the step [10d]. By such an operation, as described above, platelets do not remain in the circuit and the yield is improved.

  [13d] to [20d] Steps similar to [13a] to [20a] are performed with the pump 92 stopped.

  In such a platelet collecting method, the buffy coat is returned in step [10d] and the cleaning liquid (including platelets) is returned in step [12d] during the transfer of blood from blood reservoir 106 into rotor 42. In particular, since the buffy coat and the return of the cleaning liquid can be reliably and quickly performed by driving the pump 92, the entire processing time can be further shortened.

  In blood component separation device 1D, one end of tube 20 may not be connected to branch connector 12, but may be configured to be connected in the middle of tube 27 using a branch connector (not shown).

Next, the present invention will be described in more detail based on specific examples.
(Example 1)
Using the blood component separation apparatus 1A having the configuration shown in FIGS. 1 and 2, blood processing is performed on five blood bags with a blood storage volume of 400 ml by the steps [1a] to [20a] described above to produce a platelet preparation. It was. The conditions in each step are shown in Table 4 below.

(Example 2)
Using the blood component separation apparatus 1C having the configuration shown in FIGS. 5 and 2, the blood treatment is performed on five blood bags having a blood storage volume of 400 ml by the steps [1c] to [20c] described above to produce a platelet preparation. It was. The conditions in each corresponding step were the same as the conditions shown in Table 4 above.

(Example 3)
Using the blood component separation device 1D having the configuration shown in FIGS. 6 and 2 (however, the pump 92 is connected to the control means 7), by the steps [1d] to [20d] described above, five blood bags with a storage volume of 400 ml are obtained. The blood treatment was performed to prepare a platelet preparation. The conditions in each corresponding step were the same as the conditions shown in Table 5 above.

(Comparative example)
In the apparatus shown in FIG. 1, a surge process is performed each time five blood bags each having a blood storage volume of 400 ml are processed using a circuit having no buffy coat bag 25 and the third line 8. The collected platelets were collected as a platelet preparation.
The plasma supply in each surge process was 40 seconds at a pump discharge rate (plasma supply speed) of 220 ml / min.

[Evaluation]
With respect to the platelet preparations obtained in Examples 1 to 3 and the comparative example, the recovery amount, the platelet count, the white blood cell count, the platelet recovery rate and the treatment time were determined. The results are shown in Table 6 below. The platelet count was counted using a blood cell counter (manufactured by Toa Electronics Co., Ltd., Sysmex K-2000 type), and the white blood cell count was measured by the Negeotte chamber method.

  As shown in Table 6 above, each of Examples 1 to 3 has a higher recovery rate of platelets and a removal rate of leukocytes in the recovered platelets, and a shorter total processing time than Comparative Examples.

  As mentioned above, although this invention was demonstrated based on each Example, the circuit structure etc. which are used for the blood component separation apparatus of this invention are not limited to the thing of illustration, For example, the said 4th line 10 is a blood donor. It may be a blood removal / return line having a puncture needle for puncturing the blood vessel. Moreover, the structure which does not have any one of the said branch line for plasma collection | recovery and the said branch line for platelet collection | recovery may be sufficient. Further, a channel opening / closing means such as a valve may be provided in the middle of the tube 13 or 24. A pump may be provided in the second line 3 or the fourth line 10.

The container for temporarily storing the buffy coat is not limited to the bag as illustrated, but may be a hard container such as a bottle.
In the platelet collection method using the apparatus of the present invention, the order of the predetermined steps among the above steps may be different, an arbitrary step may be added, and a predetermined step (for example, buffy The steps of washing the coat bag and returning the washing solution may be omitted.

You may perform washing | cleaning of a buffy coat bag etc. with washing | cleaning liquids, such as physiological saline separately facilitated. In this case, the container in which the cleaning liquid is stored in advance may be connected, for example, in the middle of the third line so as to communicate with the buffy coat bag.
In addition, it cannot be overemphasized that the blood component separation apparatus of this invention is not restricted to the case where it is used for manufacture of the platelet preparation mentioned above.

It is a top view which shows typically the structure of 1st Example of the blood component separation apparatus of this invention. It is a block diagram which shows the control system of the blood component separation apparatus of this invention. It is a fragmentary sectional front view which shows the structural example of the centrifuge bowl and rotation drive device in this invention. It is a top view which shows typically the structure of 2nd Example of the blood component separation apparatus of this invention. It is a top view which shows typically the structure of 3rd Example of the blood component separation apparatus of this invention. It is a top view which shows typically the structure of 4th Example of the blood component separation apparatus of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1A-1D Blood component separation apparatus 2 1st line 3 2nd line 4 Centrifugal bowl 41 Tubing body 42 Rotor 43 Inlet 44 Outlet 45 Upper part 46 Blood storage space 47, 48 Channel 5 Rotation drive device 51 Housing 52 Leg part 53 Motor 54 Rotating shaft 55 Fixing base 551 Recessed part 56 Bolt 57 Spacer 58 Mounting member 61, 62 Optical sensor 63 Light projecting part 64 Light receiving part 7 Control means 8 Third line 83-87 Valve 91, 92 Pump 10 Fourth line DESCRIPTION OF SYMBOLS 101 Tube 102 Branch connector 103 Tube 104, 105 Blood bag 106 Blood storage part 12 Branch connector 13, 14 Tube 15 Branch connector 16 Tube 17 Platelet bag 18 Tube 19 Chamber 20 Tube 21 Plasma bag 22 Air storage bag 23, 2 4 Tube 25 Buffy coat bag 26 Tube (second tube)
27 Tube (first tube)
28, 29 Branch connector 31 Plasma layer 32 Buffy coat layer 33 Red blood cell layer B Interface

Claims (11)

A blood component separation device for separating blood into a plurality of blood components and transferring the separated blood components,
A rotatable rotor having a blood storage space therein, and an inlet and an outlet communicating with the blood storage space, and blood introduced from the inlet by rotation of the rotor is a plurality of blood in the blood storage space A centrifuge to centrifuge the components;
A first line connected to the inlet;
A second line connected to the outlet;
A buffy coat bag for storing the buffy coat;
One end is connected to the buffy coat bag, the other end is connected to the first line and / or the second line, and the third line and the first line and the second line, A fourth line for supplying blood;
A platelet bag installed or connected to the second line and storing platelets;
The blood is introduced into the blood storage space through the fourth line and the first line, and the rotor is rotated, and the blood is centrifuged to separate into a plurality of blood components. After performing at least one buffy coat collecting operation for transferring the buffy coat to the buffy coat bag through the third line,
The buffy coat in the buffy coat bag is supplied to the first line or the second line via the third line, and introduced into the blood storage space together with the blood fed from the fourth line. Perform buffy coat inflow operation,
Thereafter, the blood component separation device operates to perform a platelet collection operation for collecting platelets obtained by centrifugation through the second line into the platelet bag.   The third line has one end connected to the buffy coat bag, the other end connected to the first line, one end connected to the buffy coat bag, and the other end connected to the second line. The blood component separation device according to claim 1, further comprising a second tube connected to the line. A pump installed between a connection portion of the first line with the fourth line and a connection portion of the third line with the first tube;
The blood component separation device according to claim 2, wherein the buffy coat bag is provided such that a connection portion with the second tube of the third line faces downward.   The blood component separation device according to claim 2, further comprising a pump installed between a connection portion of the third line with the first tube in the first line and the inflow port.   The first line is installed between the connection part of the fourth line and the connection part of the third line to the first tube and in the middle of the first tube of the third line. The blood component separation device according to claim 2, further comprising a pump.   The blood component separation device according to any one of claims 1 to 5, further comprising a plasma bag that is installed or connected to the second line and stores plasma.   After the buffy coat inflow operation, the cleaning liquid is introduced into the buffy coat bag, the buffy coat bag is cleaned, and then the cleaning liquid used for the cleaning is operated to perform a cleaning operation to return to the blood storage space. Item 7. A blood component separation device according to any one of Items 1 to 6.   After the buffy coat inflow operation, plasma obtained by centrifugation is introduced into the buffy coat bag, the buffy coat bag is washed, and then the plasma subjected to the washing is returned to the blood storage space. The blood component separation device according to any one of claims 1 to 6, which operates to perform a washing operation. After the buffy coat inflow operation, plasma obtained by centrifugation is introduced into the buffy coat bag, the buffy coat bag is washed, and then the plasma subjected to the washing is returned to the blood storage space. A blood component separation device for performing a washing operation,
The washing operation introduces plasma obtained by centrifugation to the buffy coat bag through the second tube of the second line and the third line to wash the buffy coat bag, The blood according to any one of claims 2 to 6, wherein the blood subjected to the washing is returned to the blood storage space through the first tube and the first line of the third line. Component separation device.   The platelet collection operation is performed by supplying plasma at a plasma supply rate of 10 to 90 ml / min from below the blood storage space under the rotation of the rotor to float the platelets, and collecting the platelets that have flowed out from the outlet. The blood component separation device according to any one of claims 1 to 9. The blood component separation device according to any one of claims 1 to 10, wherein the fourth line includes a blood reservoir or a puncture needle.

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