WO1993021892A1 - System and method for centrifugal separation of two or more fractions from a composite liquid, and a bag intended therefor - Google Patents

System and method for centrifugal separation of two or more fractions from a composite liquid, and a bag intended therefor Download PDF

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Publication number
WO1993021892A1
WO1993021892A1 PCT/SE1993/000345 SE9300345W WO9321892A1 WO 1993021892 A1 WO1993021892 A1 WO 1993021892A1 SE 9300345 W SE9300345 W SE 9300345W WO 9321892 A1 WO9321892 A1 WO 9321892A1
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WO
WIPO (PCT)
Prior art keywords
bag
bars
cassette
separation
pair
Prior art date
Application number
PCT/SE1993/000345
Other languages
French (fr)
Inventor
Peter Unger
Eric Westberg
Erik Öhlin
Original Assignee
Seroteknik Hb
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Seroteknik Hb filed Critical Seroteknik Hb
Priority to EP93912036A priority Critical patent/EP0680311A1/en
Publication of WO1993021892A1 publication Critical patent/WO1993021892A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/029Separating blood components present in distinct layers in a container, not otherwise provided for
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0272Apparatus for treatment of blood or blood constituents prior to or for conservation, e.g. freezing, drying or centrifuging
    • A61M1/0277Frames constraining or supporting bags, e.g. during freezing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B04CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04BCENTRIFUGES
    • B04B5/00Other centrifuges
    • B04B5/04Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0407Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
    • B04B5/0428Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles with flexible receptacles

Definitions

  • the present invention relates to a system for centrifugal separation of two or more fractions from a composite liquid, such as blood, comprising a centrifuge with one or more cassettes having an internal chamber adapted to receive an elongated bag containing the liquid which is to be separated, whereby at least one cassette comprises one or more long, narrow constrictions of the internal chamber which are arranged transverse to the separation direction, and means arranged at these restrictions for clamping of the bag after separation.
  • the invention also relates to a method for centrifugal separation of two or more fractions from a composite liquid, such as blood, whereby an elongated bag is filled with said liquid and is placed in a cassette in a centrifuge and said centrifuge is provided with one or more constriction gaps arranged transverse to the separation direction, along which gaps the bag is sealed after separation.
  • the invention further relates to a bag intended to be used in the above-mentioned system for carrying out the above-mentioned method.
  • the bag includes two elongated films laid over each other which are joined to each other along the periphery whereat at least one connection nipple communicates with the interior of the bag, preferably sealed between the two films at at least the one end of the elongated bag.
  • the system according to the present invention solves the above first-mentioned problem by being provided with means for stretching the bag laterally immediately adjacent said constriction or constrictions.
  • the last-mentioned problem is solved at the same time by the fact that a second constriction and subsequent clamping of the bag does not need to occur totally within the cassette being used. This constriction and clamping can instead be carried out totally or partially after centrifuging is completed and after the cassette is opened.
  • Said means for stretching the bag preferably consists of holes arranged in the bag and location means for the holes in the cassette, for example in the form of locating studs at the ends of the constriction.
  • Said clamping means consists suitably of a pair of bars arranged parallel to the constriction, for example in a manner such as is described in the above-mentioned European and American patent.
  • the said pair of bars is arranged to be closed and opened with the help of a clamping arrangement which is arranged to allow three separate positions for the pair of bars, namely a separation position at which the pair of bars forms a narrow gap in the bag lying between the bars, a completely closed position and a fully opened position.
  • a bag suitable for the system according to the invention can consist of two flexible films laid over each other which are joined together along the periphery by means of a longitudinally extending seal, whereby at least one connection nipple is sealed between the films at at least the one end of the elongated bag.
  • a simple construction of the above-mentioned clamping arrangement is achieved if it consists of a ring which has one leg pivotably supported in the one half of said pair of bars, and a second leg which is foldable over the second half of the pair of bars or a part of that half, whereby the distance between the two legs varies in such a manner that a displacement of the ring in the longitudinal direction of the legs creates said separation position and said totally closed position.
  • the system according to the invention in a manner as described in the above said patents, can be provided with a second pair of bars which is arranged to seal the bag after separation parallel with the first pair of bars at a distance therefrom whilst the bag is still within the cassette.
  • this sealing can instead occur after the bag has been removed therefrom.
  • This second sealing of the bag can hereby occur either in the cassette after it has been opened or after the bag has been totally removed from the cassette. If the sealing occurs in the latter-mentioned way, it can be simplified with the help of a frame for suspending the bag after separation, the frame being provided with one or more additional pairs of bars for clamping the bag parallel to the first pair of bars at a distance therefrom.
  • the frame can be provided with means for displacing the bag in its longitudinal direction with respect to said additional pairs of bars in order to permit sealing between these bars substantially between two separated fractions.
  • These means for displacing the bag are suitably formed by a rotatable cylinder with attachment means for the one end of the elongated bag.
  • the cassette is suitably divided in two and arranged to be mounted together with the sealed bag in a conventional outwardly-swinging centrifuge cup in a manner as described in the above-mentioned patents.
  • the cassette is preferably provided on the inside with fastening means for locking the first-mentioned pair of bars in a fixed position in relation to the direction of separation, for example in the form of gaps arranged parallel to said constriction within the cassette.
  • the invention also includes a method for centrifugal separation of two or more fractions from a composite liquid, such as blood, whereby an elongated bag is filled with said liquid and is placed in a cassette in a centrifuge and said centrifuge is provided with one or more constriction gaps arranged transverse to the separation direction, along which gaps the bag is sealed after separation.
  • the method is characterized in that the bag is stretched in its lateral direction immediately adjacent the constriction gap.
  • the method according to the invention be used for separating various blood fractions whereby the bag is sealed along said constriction gap with the aid of a first pair of bars after separation for separating of plasma and blood cells, then the collected buffy-coat is suitably isolated with the help of one or two further pairs of bars.
  • two further pairs of bars are suitably used which are arranged parallel to the first pair and on either side thereof, whereby the first pair is removed after the two other pairs are closed and whereby the position for the two other pairs of bars is preferably adjusted after separation in relation to the visible transition layer between the different fractions.
  • the invention also includes a modified method for centrifugal separation of two or more fractions from blood, whereby an elongated bag is filled with the blood and is placed in a cassette in a centrifuge with a transverse region of the bag being adjacent a corresponding constriction gap in the cassette, which gap is arranged transverse to the direction of separation, whereby the gap is sealed with the help of a first pair of bars after the separation.
  • the method is characterized in that the bag is sealed with the help of one or more additional pairs of bars at a level corresponding to the visible fraction borders after the cassette is opened. It has been shown to be practical that the additional sealing is performed with the bag removed from the cassette and suspended in a suitable suspension arrangement, in the form of, for example, a frame provided with said additional pairs of bars.
  • the height position of the bag can hereby be easily adjusted in relation to said additional pairs of bars before the sealing of the bag therewith.
  • One possibility for separating the different separated fractions from each other is that one begins with the bag suspended first with the plasma at the top, that thereafter the buffy-coat is isolated therefrom with help of said further pair of bars, that the bag is thereafter turned upside down for removal of the plasma, that thereafter the pair of bars separating the plasma and the buffy-coat is opened or totally removed for removal of the buffy-coat, and that the viscous blood cells are diluted and preferably finally transferred to a separate collection bag therefor.
  • a blood bag is preferably used of the type which is described in the above-mentioned patents, with tube connections in both the upper and lower sections and united with separate component containers which will be described in more detail in connection with the appended drawings.
  • the separation can be performed in such a manner that the buffy-coat is first separated from remaining fractions either by means of two pairs of shutting-off bars arranged in the cassette, or by means of two outer pairs of bars.
  • the blood bag is suspended with the plasma section on top and with a bag containing a dilution solution at a higher level than the cell concentrate of the blood bag.
  • a liquid block for example a break pin, is thereafter broken between the dilution solution and cell concentrate.
  • the dilution solution flows over to the cell concentrate and dilutes it.
  • the now empty bag for the dilution solution is transferred down to the lowest practicable level where the other component bag is also located.
  • a liquid block is thereafter broken between this second component bag and the plasma fraction.
  • the diluted cell concentrate and the plasma then flow over to respective component bags which are suitably welded apart from the blood bag.
  • the shutting-off rails can thereafter be removed and the buffy-coat can be spread in the entire blood bag.
  • the invention also includes a bag intended to be used in a system of the above-defined type for carrying out the described method, including two elongated films laid over each other which are joined to each other along the periphery, whereat at least one connection nipple communicates with the interior of the bag, preferably sealed between the two films at at least the one end of the bag.
  • the bag is characterized by means for stretching the bag in its lateral direction which are arranged opposite each other close to respective longitudinal edges in suitable positions in relation to the size of the fractions which are to be separated. Said means for stretching the bag in its lateral direction is suitably in the form of two reinforced holes arranged within the outer edge of the bag, though external to the inner sealed section of the bag.
  • the bag according to the invention is provided at at least its one end with means for its suspension, in the form of holes, slots etc. These means can first be used for fixing the bag in the cassette and thereafter also used for suspending the bag in connection with emptying of the various fractions.
  • the bag is provided with these means for its suspension at both of its ends. In this manner it can be locked within the cassette at both its ends, whilst after its removal from the cassette it can be suspended either in a first position or in a second position totally inverted with respect to the first position, for carrying out the separation method first mentioned above.
  • the bag is provided with at least one connection nipple at each end.
  • said means for stretching the bag in its lateral direction is in the form of a thickening of the bags material around the holes provided for this purpose.
  • the . bag according to the invention is also preferably provided with reinforcements along at least its longitudinal edges in the form of thickening of the bag material. Even these thickenings can be used for fixing the bag in the cassette.
  • the bag according to the invention preferably forms a part of a preferably totally closed set of bags including a supply conduit for the liquid which is to be separated, at least one outlet conduit for the various fractions, collection bags for the various fractions and preferably also a bag containing dilution means for the most viscous fraction, for example the separated blood cells.
  • Fig. 1 shows an example of a blood separation bag according to the invention.
  • Fig. 2 shows the same bag together with a lower clamping bar provided with two locking rings.
  • Fig. 3 shows the bag provided with an upper clamping bar and with the rings swung thereover.
  • Fig. 4 shows the bag seen from the side with the clamping bars separated from each other.
  • the bag is shown here with its halves filled with the liquid which is to be separated.
  • Fig. 5 shows a view corresponding to Fig. 4, though with the clamping bars in a closed position.
  • Fig. 6 shows a small cut out section from the bag intended to be placed immediately adjacent the clamping bars.
  • Fig. 7 shows a section through the part of the bags shown in Fig. 6.
  • Fig. 8 shows how the bag can be separated into three regions with help of an extra pair of bars.
  • Fig. 9 shows the bag placed in a cassette after centrifuging together with a first pair of bars and one or more additional bags intended to receive the separated fractions.
  • the cassette is in turn placed in a conventional centrifuge cup.
  • Fig. 10 and 11 show the bag centrifuged and suspended from a frame.
  • Fig. 12 shows a complete set of bags with the bag according to the invention combined with further bags intended to receive the separated fractions.
  • Figs. 13, 14 and 15 finally show schematically in three steps how fractioning can be carried out with help of the system and method according to the invention.
  • the blood separation bag 1 shown in Fig. l is modified compared to standard bags. It is made from two laid over films which are joined by means of a weld 3 a little way within the outer edge or periphery 2. At least two pre-made or stamped-out holes 4 are provided between the periphery 2 and the weld 3. The bag is further provided with a slot 5 and two suspension holes 6. Finally it is provided with at least two connection nipples or connection tubes which are suitably formed by plastic tubes welded between the plastic films. In the shown example the bag 1 is provided with four connection nipples, i.e. two connection nipples 7 at the one end and two connection nipples 7' at the other end. The bag is shown in Fig.
  • Two rings 9 are pivotably carried by the bar and include a first leg 10 which is carried by the bar 8 and a second leg 11.
  • the second leg 11 is divided into two different regions 11a and lib at different distances from the legs 10.
  • Two locating pins are denoted by 4' on which the holes 4 are intended to be located when the bag is placed in the cassette shown in Fig. 9.
  • Fig. 3 the bag 1 is shown provided with a second clamping bar 12 and with the rings 9 folded over this bar
  • Fig. 4 the bag 1 is shown from the side in a full condition with the clamping bars 8 and 12 shown in a separation position, that is to say slightly apart.
  • the shown ring 9 is here folded over a section of the bar 12 and inserted in a slot 13 therein.
  • Fig. 5 shows a view corresponding to that of Fig. 4, though with the ring 9 displaced to a clamping position.
  • a comparison between Fig. 2, 4 and 5 shows that the ring 9 in the separation position shown in Fig. 4 has the region lib in the slot 13.
  • the region 11a is instead inserted in the slot 13 with the result that the bars 8 and 12 are clamped against each other.
  • Figs. 6 and 7 show a plan view and a section respectively through a small part of the bag 1.
  • a thickening 14 can be achieved which reinforces the hole 4 and which thickening can also extend further in the bag's longitudinal direction just within the edge 2 to form a stiffening of the bag.
  • Fig. 8 it is shown how the system according to the invention can be complemented by a second pair of bars 15.
  • the bars can, as is shown in the above-mentioned patents, be arranged within the cassette, whereby the bag must have at least four edge holes. Alternatively, the bars can be added after the bag is taken from the cassette or at least once the cassette is opened after separation is completed.
  • the bag 1 is shown in Fig. 9 inserted in a cassette
  • Figs. 10 and 11 shown the bag 1 suspended on a frame which is denoted in its entirety by 18.
  • the bag is shown after separation and suspended from two guide pegs 19 on a cylinder 20.
  • the cylinder can be rotated thanks to a bearing support 22, thereby achieving a raising or lowering of the bag 1.
  • the frame post 23 also carries two pairs of bars 24 and 25 respectively.
  • the lower bars of the respective pairs of bars are shown in Fig. 10 and these with dashed lines.
  • the bag contains plasma in its upper region la and blood cells in the lower region lb. Within the region lc on either side of the tension bars there is a collecting of buffy-coat.
  • pairs of bars 24 and 25 which are adjustable in the height direction.
  • the pair of bars 8, 12 can be removed. Should the buffy-coat, because of high or low haematocrit, be totally above or below the pair of bars 8, 12, then it is only necessary that one of the pairs of bars 24 and 25 be used.
  • Two manoeuvre wheels are denoted by 26 and 27 and are used for manoeuvring the pairs of bars 24 and 25.
  • Fig. 10 the pairs of bars 24 and 25 are shown separated by a distance piece 28, which pairs are intended to be displaced at the same time together with this piece upwardly or downwardly.
  • Fig. 12 An entire set of bags according to the invention is shown in Fig. 12.
  • Figs. 13, 14 and 15 are intended to illustrate in three steps how the set of bags according to Fig. 12 can be employed to separate the various blood fractions.
  • the blood bag 1 is shown provided with an anticoagulant solution (to prevent blood coagulation) connected via a liquid block (for example a break pin) 31 and tube 32 to a plasma component bag 33.
  • a blood cell component bag 36 is connected via a tube 34 and a liquid block 35.
  • the bag 36 contains a diluting and nutrient solution 37 (known as SAGM) .
  • SAGM diluting and nutrient solution
  • the bag 1 has two further connections, namely a connection to a blood flow tube 38 with a needle, and a connector 39 which can be used to remove the buffy-coat from the bag 1 in a sterile manner at a final stage.
  • a connection to a blood flow tube 38 with a needle and a connector 39 which can be used to remove the buffy-coat from the bag 1 in a sterile manner at a final stage.
  • a connector 39 which can be used to remove the buffy-coat from the bag 1 in a sterile manner at a final stage.
  • the blood has been supplied to the bag
  • the filled blood bag 1 has, in a manner as described previously, been inserted in the cassette 16 and centrifuged to the three components plasma 40, cell concentrate 41 and buffy-coat 42.
  • the buffy-coat in Fig. 14 has been isolated in the volume lc, the plasma in the volume la and the cell concentrate in the volume lb.
  • the bag 1 has been suspended on a frame 18' with the plasma section la furthest up and with a bag 36 with dilution solution 37 for the cells at a higher level than the cell concentrate section lb.
  • the solution 37 can flow to the volume lb and dilute the viscous cell concentrate therein.
  • Fig. 15 the now empty bag 37 has been moved to the lowest practical level where the bag 33 is also located.
  • the plasma and the cell concentrate diluted by the solution 37 can flow down into respective component bags which thereafter can be sealed off, or in another manner isolated, for separate uses.
  • the blocking rails are thereafter removed so the buffy-coat can spread out in the entire bag 1 and when necessary removed via the connection 39.

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  • Heart & Thoracic Surgery (AREA)
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Abstract

System, method and bag for centrifugal separation of two or more fractions from a composite liquid, for example blood, comprising a centrifuge with one or more cassettes (16) with an internal chamber adapted for receiving an elongated bag (1) containing the liquid which is to be separated, whereby at least one cassette (16) comprises one or more long, narrow constrictions of the internal chamber which are arranged transverse to the separation direction, and means (8, 12) arranged at these constrictions for clamping of the bag (1) after separation. The system according to the invention is characterized by means (4, 4') for stretching the bag (1) laterally immediately adjacent said constrictions. The bag (1) can be arranged to be sealed with help of one or more pairs of bars (8, 12; 15; 24, 25) at the boundary layers for the various fractions. These pairs of bars can be arranged within and/or outside said cassette.

Description

TITLE:
System and method for centrifugal separation of two or more fractions from a composite liquid, and a bag intended therefor.
TECHNICAL FIELD:
The present invention relates to a system for centrifugal separation of two or more fractions from a composite liquid, such as blood, comprising a centrifuge with one or more cassettes having an internal chamber adapted to receive an elongated bag containing the liquid which is to be separated, whereby at least one cassette comprises one or more long, narrow constrictions of the internal chamber which are arranged transverse to the separation direction, and means arranged at these restrictions for clamping of the bag after separation.
The invention also relates to a method for centrifugal separation of two or more fractions from a composite liquid, such as blood, whereby an elongated bag is filled with said liquid and is placed in a cassette in a centrifuge and said centrifuge is provided with one or more constriction gaps arranged transverse to the separation direction, along which gaps the bag is sealed after separation.
The invention further relates to a bag intended to be used in the above-mentioned system for carrying out the above-mentioned method. The bag includes two elongated films laid over each other which are joined to each other along the periphery whereat at least one connection nipple communicates with the interior of the bag, preferably sealed between the two films at at least the one end of the elongated bag. BACKGROUND OF THE INVENTION:
A system, method and a bag according to the above- mentioned definitions are described in European patent EP- Bl-0 148 182 and its corresponding American patent TJS-A- 4 617 009. In the described known art it has been shown that difficulties can arise through the bag creasing within the region of the transverse constrictions. Furthermore, in a conventional centrifuge having conventionally sized centrifugal cups and conventional type of blood bags, it has been shown to be difficult to achieve room with a cassette with more than one constriction. One reason for this difficulty is that, when using more than one constriction, it is easy to obtain unsuitable angles of the cassette's inner chamber or crease formation of the top region of the blood bag and/or immediately adjacent the transverse constrictions.
SUMMARY OF THE INVENTION:
The system according to the present invention solves the above first-mentioned problem by being provided with means for stretching the bag laterally immediately adjacent said constriction or constrictions. The last-mentioned problem is solved at the same time by the fact that a second constriction and subsequent clamping of the bag does not need to occur totally within the cassette being used. This constriction and clamping can instead be carried out totally or partially after centrifuging is completed and after the cassette is opened.
Said means for stretching the bag preferably consists of holes arranged in the bag and location means for the holes in the cassette, for example in the form of locating studs at the ends of the constriction. In this way a very simple construction is attained which does not unduly increase the costs of either the bag or the cassette. Said clamping means consists suitably of a pair of bars arranged parallel to the constriction, for example in a manner such as is described in the above-mentioned European and American patent. In a preferred embodiment of the system according to the invention the said pair of bars is arranged to be closed and opened with the help of a clamping arrangement which is arranged to allow three separate positions for the pair of bars, namely a separation position at which the pair of bars forms a narrow gap in the bag lying between the bars, a completely closed position and a fully opened position.
A bag suitable for the system according to the invention can consist of two flexible films laid over each other which are joined together along the periphery by means of a longitudinally extending seal, whereby at least one connection nipple is sealed between the films at at least the one end of the elongated bag.
A simple construction of the above-mentioned clamping arrangement is achieved if it consists of a ring which has one leg pivotably supported in the one half of said pair of bars, and a second leg which is foldable over the second half of the pair of bars or a part of that half, whereby the distance between the two legs varies in such a manner that a displacement of the ring in the longitudinal direction of the legs creates said separation position and said totally closed position.
The system according to the invention, in a manner as described in the above said patents, can be provided with a second pair of bars which is arranged to seal the bag after separation parallel with the first pair of bars at a distance therefrom whilst the bag is still within the cassette. Alternatively, this sealing can instead occur after the bag has been removed therefrom. This second sealing of the bag can hereby occur either in the cassette after it has been opened or after the bag has been totally removed from the cassette. If the sealing occurs in the latter-mentioned way, it can be simplified with the help of a frame for suspending the bag after separation, the frame being provided with one or more additional pairs of bars for clamping the bag parallel to the first pair of bars at a distance therefrom.
The frame can be provided with means for displacing the bag in its longitudinal direction with respect to said additional pairs of bars in order to permit sealing between these bars substantially between two separated fractions. These means for displacing the bag are suitably formed by a rotatable cylinder with attachment means for the one end of the elongated bag.
The cassette is suitably divided in two and arranged to be mounted together with the sealed bag in a conventional outwardly-swinging centrifuge cup in a manner as described in the above-mentioned patents.
Because of the forces which arise during centrifuging, the cassette is preferably provided on the inside with fastening means for locking the first-mentioned pair of bars in a fixed position in relation to the direction of separation, for example in the form of gaps arranged parallel to said constriction within the cassette.
As mentioned above, the invention also includes a method for centrifugal separation of two or more fractions from a composite liquid, such as blood, whereby an elongated bag is filled with said liquid and is placed in a cassette in a centrifuge and said centrifuge is provided with one or more constriction gaps arranged transverse to the separation direction, along which gaps the bag is sealed after separation. According to the invention the method is characterized in that the bag is stretched in its lateral direction immediately adjacent the constriction gap. Should the method according to the invention be used for separating various blood fractions whereby the bag is sealed along said constriction gap with the aid of a first pair of bars after separation for separating of plasma and blood cells, then the collected buffy-coat is suitably isolated with the help of one or two further pairs of bars.
For unknown haematocrit values (cell content) two further pairs of bars are suitably used which are arranged parallel to the first pair and on either side thereof, whereby the first pair is removed after the two other pairs are closed and whereby the position for the two other pairs of bars is preferably adjusted after separation in relation to the visible transition layer between the different fractions.
The invention also includes a modified method for centrifugal separation of two or more fractions from blood, whereby an elongated bag is filled with the blood and is placed in a cassette in a centrifuge with a transverse region of the bag being adjacent a corresponding constriction gap in the cassette, which gap is arranged transverse to the direction of separation, whereby the gap is sealed with the help of a first pair of bars after the separation. The method is characterized in that the bag is sealed with the help of one or more additional pairs of bars at a level corresponding to the visible fraction borders after the cassette is opened. It has been shown to be practical that the additional sealing is performed with the bag removed from the cassette and suspended in a suitable suspension arrangement, in the form of, for example, a frame provided with said additional pairs of bars. The height position of the bag can hereby be easily adjusted in relation to said additional pairs of bars before the sealing of the bag therewith. One possibility for separating the different separated fractions from each other is that one begins with the bag suspended first with the plasma at the top, that thereafter the buffy-coat is isolated therefrom with help of said further pair of bars, that the bag is thereafter turned upside down for removal of the plasma, that thereafter the pair of bars separating the plasma and the buffy-coat is opened or totally removed for removal of the buffy-coat, and that the viscous blood cells are diluted and preferably finally transferred to a separate collection bag therefor.
A blood bag is preferably used of the type which is described in the above-mentioned patents, with tube connections in both the upper and lower sections and united with separate component containers which will be described in more detail in connection with the appended drawings.
By using such a set of bags the separation can be performed in such a manner that the buffy-coat is first separated from remaining fractions either by means of two pairs of shutting-off bars arranged in the cassette, or by means of two outer pairs of bars. Hereafter the blood bag is suspended with the plasma section on top and with a bag containing a dilution solution at a higher level than the cell concentrate of the blood bag. A liquid block, for example a break pin, is thereafter broken between the dilution solution and cell concentrate. In this manner the dilution solution flows over to the cell concentrate and dilutes it. Thereafter the now empty bag for the dilution solution is transferred down to the lowest practicable level where the other component bag is also located. A liquid block is thereafter broken between this second component bag and the plasma fraction. The diluted cell concentrate and the plasma then flow over to respective component bags which are suitably welded apart from the blood bag. The shutting-off rails can thereafter be removed and the buffy-coat can be spread in the entire blood bag.
As mentioned above, the invention also includes a bag intended to be used in a system of the above-defined type for carrying out the described method, including two elongated films laid over each other which are joined to each other along the periphery, whereat at least one connection nipple communicates with the interior of the bag, preferably sealed between the two films at at least the one end of the bag. The bag is characterized by means for stretching the bag in its lateral direction which are arranged opposite each other close to respective longitudinal edges in suitable positions in relation to the size of the fractions which are to be separated. Said means for stretching the bag in its lateral direction is suitably in the form of two reinforced holes arranged within the outer edge of the bag, though external to the inner sealed section of the bag.
Preferably, the bag according to the invention is provided at at least its one end with means for its suspension, in the form of holes, slots etc. These means can first be used for fixing the bag in the cassette and thereafter also used for suspending the bag in connection with emptying of the various fractions. Suitably the bag is provided with these means for its suspension at both of its ends. In this manner it can be locked within the cassette at both its ends, whilst after its removal from the cassette it can be suspended either in a first position or in a second position totally inverted with respect to the first position, for carrying out the separation method first mentioned above.
A reduced risk of mixing of the various fractions is obtained if the bag is provided with at least one connection nipple at each end. In a preferred embodiment of the bag according to the invention said means for stretching the bag in its lateral direction is in the form of a thickening of the bags material around the holes provided for this purpose.
The .bag according to the invention is also preferably provided with reinforcements along at least its longitudinal edges in the form of thickening of the bag material. Even these thickenings can be used for fixing the bag in the cassette.
The bag according to the invention preferably forms a part of a preferably totally closed set of bags including a supply conduit for the liquid which is to be separated, at least one outlet conduit for the various fractions, collection bags for the various fractions and preferably also a bag containing dilution means for the most viscous fraction, for example the separated blood cells.
BRIEF DESCRIPTION OF THE DRAWINGS: Fig. 1 shows an example of a blood separation bag according to the invention.
Fig. 2 shows the same bag together with a lower clamping bar provided with two locking rings.
Fig. 3 shows the bag provided with an upper clamping bar and with the rings swung thereover.
Fig. 4 shows the bag seen from the side with the clamping bars separated from each other. The bag is shown here with its halves filled with the liquid which is to be separated. Fig. 5 shows a view corresponding to Fig. 4, though with the clamping bars in a closed position.
Fig. 6 shows a small cut out section from the bag intended to be placed immediately adjacent the clamping bars. Fig. 7 shows a section through the part of the bags shown in Fig. 6. Fig. 8 shows how the bag can be separated into three regions with help of an extra pair of bars.
Fig. 9 shows the bag placed in a cassette after centrifuging together with a first pair of bars and one or more additional bags intended to receive the separated fractions. The cassette is in turn placed in a conventional centrifuge cup.
Fig. 10 and 11 show the bag centrifuged and suspended from a frame. Fig. 12 shows a complete set of bags with the bag according to the invention combined with further bags intended to receive the separated fractions.
Figs. 13, 14 and 15 finally show schematically in three steps how fractioning can be carried out with help of the system and method according to the invention.
DETAILED DESCRIPTION OF THE SYSTEM, METHOD AND BAG ACCORDING TO THE INVENTION:
The blood separation bag 1 shown in Fig. l is modified compared to standard bags. It is made from two laid over films which are joined by means of a weld 3 a little way within the outer edge or periphery 2. At least two pre-made or stamped-out holes 4 are provided between the periphery 2 and the weld 3. The bag is further provided with a slot 5 and two suspension holes 6. Finally it is provided with at least two connection nipples or connection tubes which are suitably formed by plastic tubes welded between the plastic films. In the shown example the bag 1 is provided with four connection nipples, i.e. two connection nipples 7 at the one end and two connection nipples 7' at the other end. The bag is shown in Fig. 2 together with a clamping bar 8 which shall hereinafter be referred to as the lower bar. Two rings 9 are pivotably carried by the bar and include a first leg 10 which is carried by the bar 8 and a second leg 11. The second leg 11 is divided into two different regions 11a and lib at different distances from the legs 10. Two locating pins are denoted by 4' on which the holes 4 are intended to be located when the bag is placed in the cassette shown in Fig. 9.
In Fig. 3 the bag 1 is shown provided with a second clamping bar 12 and with the rings 9 folded over this bar
12, which hereinafter will be referred to as the upper bar.
In Fig. 4 the bag 1 is shown from the side in a full condition with the clamping bars 8 and 12 shown in a separation position, that is to say slightly apart. The shown ring 9 is here folded over a section of the bar 12 and inserted in a slot 13 therein.
Fig. 5 shows a view corresponding to that of Fig. 4, though with the ring 9 displaced to a clamping position. A comparison between Fig. 2, 4 and 5 shows that the ring 9 in the separation position shown in Fig. 4 has the region lib in the slot 13. In the clamping position shown in Fig. 5 the region 11a is instead inserted in the slot 13 with the result that the bars 8 and 12 are clamped against each other.
Figs. 6 and 7 show a plan view and a section respectively through a small part of the bag 1. Here it is shown how by building up the weld 3 a thickening 14 can be achieved which reinforces the hole 4 and which thickening can also extend further in the bag's longitudinal direction just within the edge 2 to form a stiffening of the bag. In Fig. 8 it is shown how the system according to the invention can be complemented by a second pair of bars 15. The bars can, as is shown in the above-mentioned patents, be arranged within the cassette, whereby the bag must have at least four edge holes. Alternatively, the bars can be added after the bag is taken from the cassette or at least once the cassette is opened after separation is completed. The bag 1 is shown in Fig. 9 inserted in a cassette
16 which in turn is inserted in a substantially conventional centrifuge cup 17. The bag 1 is shown after separation is completed, though before clamping of the pair of bars 8, 12. If it is blood which has been separated, then the section la is filled with plasma and the section lb with blood cells. In the region lc therebetween is the buffy-coat fraction. 16a denotes an insert which is arranged to cover at least the lower portion of the cassette's separation plane 16b. In this way penetration of the wall of the bag 1 between the cassette halves is prevented. Two weights 16c are also shown in Fig. 9 which are arranged to press the bag 1 together at the one end which is positioned nearest the centre of rotation. These weights 16c are suitably arranged to be freely movable in guides in both cassette halves to achieve a stretching of the bag wall during centrifuging.
Figs. 10 and 11 shown the bag 1 suspended on a frame which is denoted in its entirety by 18. The bag is shown after separation and suspended from two guide pegs 19 on a cylinder 20. With help of a lever or similar 21, the cylinder can be rotated thanks to a bearing support 22, thereby achieving a raising or lowering of the bag 1. The frame post 23 also carries two pairs of bars 24 and 25 respectively. For the sake of clarity only the lower bars of the respective pairs of bars are shown in Fig. 10 and these with dashed lines. If it is blood which is being separated, then the bag contains plasma in its upper region la and blood cells in the lower region lb. Within the region lc on either side of the tension bars there is a collecting of buffy-coat. This can be isolated with help of the pairs of bars 24 and 25 which are adjustable in the height direction. When these pairs of bars have been clamped together, the pair of bars 8, 12 can be removed. Should the buffy-coat, because of high or low haematocrit, be totally above or below the pair of bars 8, 12, then it is only necessary that one of the pairs of bars 24 and 25 be used. Two manoeuvre wheels are denoted by 26 and 27 and are used for manoeuvring the pairs of bars 24 and 25. In Fig. 10 the pairs of bars 24 and 25 are shown separated by a distance piece 28, which pairs are intended to be displaced at the same time together with this piece upwardly or downwardly. Naturally, the pairs of bars 24 and 25 could also be arranged for independent displacement in order to allow separation of either smaller or larger intermediate fractions. An entire set of bags according to the invention is shown in Fig. 12. Figs. 13, 14 and 15 are intended to illustrate in three steps how the set of bags according to Fig. 12 can be employed to separate the various blood fractions. In Fig. 3 the blood bag 1 is shown provided with an anticoagulant solution (to prevent blood coagulation) connected via a liquid block (for example a break pin) 31 and tube 32 to a plasma component bag 33. To the other end of the bag 1 a blood cell component bag 36 is connected via a tube 34 and a liquid block 35. The bag 36 contains a diluting and nutrient solution 37 (known as SAGM) . As shown in Fig. 12, the bag 1 has two further connections, namely a connection to a blood flow tube 38 with a needle, and a connector 39 which can be used to remove the buffy-coat from the bag 1 in a sterile manner at a final stage. In Fig. 13 the blood has been supplied to the bag
1 and the flow tube 38 welded off. The filled blood bag 1 has, in a manner as described previously, been inserted in the cassette 16 and centrifuged to the three components plasma 40, cell concentrate 41 and buffy-coat 42.
In a similarly described manner, the buffy-coat in Fig. 14 has been isolated in the volume lc, the plasma in the volume la and the cell concentrate in the volume lb. In addition the bag 1 has been suspended on a frame 18' with the plasma section la furthest up and with a bag 36 with dilution solution 37 for the cells at a higher level than the cell concentrate section lb. When the liquid block 35 is broken, the solution 37 can flow to the volume lb and dilute the viscous cell concentrate therein.
In Fig. 15 the now empty bag 37 has been moved to the lowest practical level where the bag 33 is also located. When the liquid block 31 is also opened, the plasma and the cell concentrate diluted by the solution 37 can flow down into respective component bags which thereafter can be sealed off, or in another manner isolated, for separate uses. The blocking rails are thereafter removed so the buffy-coat can spread out in the entire bag 1 and when necessary removed via the connection 39.
The invention is not restricted solely to the above described embodiments, but can be varied within the scope of the appended claims. For example the structural components have been illustrated very schematicallyin the various figures. In practice it can therefore be necessary that in certain respects these are modified regarding both form and function.

Claims

1. System for centrifugal separation of two or more fractions from a composite liquid, such as blood, comprising a centrifuge with one or more cassettes (16) with an internal chamber adapted for receiving an elongated bag (1) containing the liquid which is to be separated, whereby at least one cassette (16) comprises one or more long, narrow constrictions of the internal chamber which are arranged transverse to the separation direction, and means (8, 12) arranged at these restrictions for clamping of the bag (1) after separation, characterized by means (4, 4') for stretching the bag laterally immediately adjacent said constriction.
2. System according to claim 1, characterized in that said means for stretching the bag (1) comprises holes (4) arranged in the bag and location means for these holes arranged in the cassette (16) , for example in the form of locating studs (4') at ends of the constriction.
3. System according to claim 1 or 2, characterized in that said means for clamping the bag (1) comprises a pair of bars (8, 12) arranged parallel to the constriction.
4. System according to claim 3, characterized in that said pair of bars (8, 12) is arranged to be closed and opened with help of a clamping arrangement (9) which is arranged to allow three separate positions of the pair of bars, that is a separation position at which the pair of bars forms a narrow gap in the bag (1) positioned between the bars, a completely closed position and a fully opened position.
5. System according to any one of the previous claims, characterized in that the bag (1) consists of two flexible films laid over each other which are bonded together along an elongated join (3) , whereby at least one connection nipple (7) is sealed between the two films at at least the one end of the elongated bag (1) .
6. System according to claim 4, characterized in that said clamping arrangement is in the form of a ring (9) which has one leg (10) pivotably supported in the one half
(8) of said pair of bars (8, 12), and a second leg (11) which is foldable over the second half (12) of the pair of bars (8, 12) or a portion of that half, whereby the distance between the two legs (10) and (11) varies in such a manner that a displacement of the ring (9) in the longitudinal direction of the legs achieves said separation position and said totally closed position respectfully.
7. System according to any one of the previous claims, characterized by a second pair of bars (15) which is arranged parallel to the first pair of bars (8, 12) and at a distance therefrom for sealing the bag (1) after separation, either whilst the bag (1) is still in the cassette (16) or after it has been removed therefrom.
8. System according to any one of the previous claims, characterized by a frame (18) for suspending the bag (1) after separation, the frame being provided with one or more additional pairs of bars (24, 25) for clamping the bag (1) parallel to the first pair of bars (8, 12) and at a distance therefrom.
9. System according to claim 8, characterized by means (19-21) for displacing the bag (1) in its direction of elongation with respect to said additional pair of bars (24, 25) to permit sealing between these bars substantially between two separated fractions.
10. System according to claim 9, characterized in that said means for displacing the bag (1) comprises a rotatable cylinder (20) with attachment means (19) for the one end of the elongated bag (1) .
11. System according to any one of the previous claims, characterized in that the cassette (16) is divided in two and arranged to be mounted together with the sealed bag (1) in a conventional outwardly swingable centrifuge cup (17) . 12. System according to any one of claims 3-11, characterized in that the cassette (16) has internal fastening means for locking the first-mentioned pair of bars (8,
12) in a fixed position in relation to the direction of separation, for example in the form of a gap within the cassette (16) arranged parallel to said constriction.
13. System according to claim 11, comprising means (16a) for varying the volume of the inner chamber in the two-part cassette (16) , characterized in that these means are arranged to at least partially follow the cassette's plane of separation (16b) in order to prevent the wall of the bag penetrating between the cassette halves.
14. System according to any one of the previous claims, characterized by means (16c) arranged to press together the bag (1) during centrifuge.
15. System according to claim 14, characterized in that said means (16c) for pressing together the bag (1) comprises one or more displaceable weights or pistons (16c) arranged nearest the centre of rotation.
16. Method for centrifugal separation of two or more fractions from a composite liquid, such as blood, whereby an elongated bag (1) is filled with said liquid and is placed in a cassette (16) in a centrifuge and said centrifuge is provided with one or more constriction gaps arranged transverse to the separation direction, along which gaps the bag (1) is sealed after separation, characterized in that the bag is stretched in its lateral direction immediately adjacent the constriction gap (gaps) .
17. Method according to claim 16, for separating various blood fractions, whereby the bag (1) is sealed along said constriction gap with help of a first pair of bars (8, 12) after separation in order to separate plasma and blood cells, characterized in that buffy-coat collected therebetween is isolated with help of one or two further pairs of bars (15, 24, 25).
18. Method according to claim 17, characterized in that with unknown haematocrit values (cell content) two further pairs of bars (24, 25) arranged parallel to the first pair and on either side thereof are used, whereby the first pair (.8, 12) is removed after the two other pairs (24, 25) are closed and whereby the position for both the further pairs of bars is preferably adjusted after the separation in relation to the visible transition layer between the various fractions.
19. Method for centrifugal separation of two or more fractions from blood, whereby the blood is filled in a elongated bag (1) which is placed in a cassette (16) in a centrifuge in a transverse region of the bag (1) positioned adjacent a corresponding constriction gap in the cassette (16) , which gap is transverse with respect to the direction of separation, whereby the gap is sealed with help of a first pair of bars (8, 12) after the separation, characterized in that the bag is sealed with help of one or more additional pairs of bars (15, 24, 25) in line with visible fraction limits after which the cassette (16) is opened.
20. Method according to claim 19, characterized in that the further sealing is carried out with the bag (1) removed from the cassette (16) and suspended in a suitable suspension arrangement, for example a frame (18) provided with said additional pair of bars (24, 25) .
21. Method according to claim 20, characterized in that the bag's (1) height position is adjusted in relation to said additional pair of bars (24, 25) before the sealing of the bag (1) therewith.
22. Method according to any of claims 16-21, characterized in that when using a two-part cassette (16) , the division line (16b) between the cassette halves is sealed at least partially with help of an insert (16a) in order to prevent the wall of the bag (1) extending between the cassette halves.
23. Method according to any one of claims 13-22, characterized in that the bag (1) is pressed together during the centrifuging by specially arranged means (16c) therefore.
24. Method according to claim 23, characterized in that said means (16c) comprises one or more displaceable weights or pistons (16c) which are arranged to act on the bag (1) at the end thereof which is facing the centre of rotation.
25. Bag intended to be used in a system according to any one of claims 1-12, including two elongated films laid over each other which are joined to each other along the periphery (2) , whereat at least one connection nipple (7) communicates with the interior of the bag (1) , preferably sealed between the two films at at least the one end of the elongated bag (1) , characterized by means (4) for stretching the bag (1) in its lateral direction arranged opposite each other close to respective longitudinal edges in suitable positions in relation to the size of the fractions which are to be separated.
26. Bag according to claim 25, characterized in that said means for stretching the bag in its transverse direction is in the form of two or more preferably reinforced holes (4) arranged within the outer edge (2) of the bag, but exterior to the inner sealed volume of the bag.
27. Bag according to claim 25 or 26, characterized in that it is provided with means (5, 6, 6) at at least its one end for suspending the bag, for example in the form of holes, slots or similar.
28. Bag according to claim 27, characterized in that it is provided with said means (5, 6, 6) for its suspension at both its ends.
29. Bag according to any one of claims 25-28, characterized in that it is provided with at least one connection nipple (7, 7' respectively) at either end.
30. Bag according to any one of claims 25-29, characterized in that said means for stretching the bag in its transverse direction are in the form of a thickening (14) of the bag material around the hole (4) or similar for that purpose.
31. Bag according to any one of claims 25-30, characterized by strengthenings (14) in the form of thickenings of the bag material around at least the bag's longitudinal edges.
32. Bag according to any one of claims 25-31, characterized in that it forms apart of a preferably totally sealed set of bags (1, 33, 36), including a supply conduit (38) for the liquid which is to be separated, at least one outlet conduit (32, 34) for the various fractions and collection bags (33, 36) for the various fractions, whereby preferably one bag (36) contains dilution means (37) for the most viscous fraction, for example separated blood cells.
PCT/SE1993/000345 1992-04-23 1993-04-21 System and method for centrifugal separation of two or more fractions from a composite liquid, and a bag intended therefor WO1993021892A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP93912036A EP0680311A1 (en) 1992-04-23 1993-04-21 System and method for centrifugal separation of two or more fractions from a composite liquid, and a bag intended therefor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9201279A SE9201279L (en) 1992-04-23 1992-04-23 SYSTEM AND PROCEDURE FOR CENTRIFUGAL SEPARATION OF TWO OR MORE FRACTIONS FROM A COMPOSITIVE SCIENCE AND THEREFORE DETERMINED PASSAGE BY Means TO STRAIGHT THE PASS TO DIVISE
SE9201279-8 1992-04-23

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000002664A1 (en) * 1998-07-13 2000-01-20 Novartis Ag Centrifuge bag-holding device with clamp assembly and uses thereof
DE10316598A1 (en) * 2003-04-11 2004-10-28 Andreas Hettich Gmbh & Co. Kg Centrifuge for the recovery of biological fluids e.g. thrombocytes from whole blood, has slits at the rotor periphery to take suspension hooks for the bodies containing the sample tubes
EP1663800A2 (en) * 2003-09-22 2006-06-07 Battelle Memorial Institute Press for removing supernatant from a flexible vessel
WO2010137884A2 (en) * 2009-05-27 2010-12-02 (주)차바이오메드 Centrifugal separation method, centrifugal separation apparatus, and bag for centrifugal separation
WO2011122844A2 (en) * 2010-04-02 2011-10-06 (주)차바이오메드 Bag for centrifugal separation and centrifugal separation method using the bag for centrifugal separation
WO2011071353A3 (en) * 2009-12-07 2011-11-10 Jeon Min-Yong Centrifuge tube
KR101091052B1 (en) * 2009-02-23 2011-12-08 차의과학대학교 산학협력단 Device for centrifugal separation and method using the same
KR20170002162A (en) * 2015-06-29 2017-01-06 노정자 Kit for separating blood and method for separating blood

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DE2950791A1 (en) * 1978-12-20 1980-07-10 Max Dr Laszczower FLEXIBLE, BAG-LIKE CONTAINER MADE OF PLASTIC TO ACQUIRE BLOOD OR. BLOOD COMPONENTS
EP0132632A2 (en) * 1983-07-21 1985-02-13 Abbott Laboratories Compartmented flexible solution container
US4617009A (en) * 1982-11-26 1986-10-14 Seroteknik Hg Method and apparatus for centrifugal batch separation of blood

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US3257072A (en) * 1963-01-07 1966-06-21 Cryogenic Eng Co Whole blood storage structure
US3545671A (en) * 1967-02-14 1970-12-08 Eugene Ross Lab Inc Apparatus for and method of collecting,storing,separating and dispensing blood and blood components
DE2950791A1 (en) * 1978-12-20 1980-07-10 Max Dr Laszczower FLEXIBLE, BAG-LIKE CONTAINER MADE OF PLASTIC TO ACQUIRE BLOOD OR. BLOOD COMPONENTS
US4617009A (en) * 1982-11-26 1986-10-14 Seroteknik Hg Method and apparatus for centrifugal batch separation of blood
EP0132632A2 (en) * 1983-07-21 1985-02-13 Abbott Laboratories Compartmented flexible solution container

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000002664A1 (en) * 1998-07-13 2000-01-20 Novartis Ag Centrifuge bag-holding device with clamp assembly and uses thereof
DE10316598A1 (en) * 2003-04-11 2004-10-28 Andreas Hettich Gmbh & Co. Kg Centrifuge for the recovery of biological fluids e.g. thrombocytes from whole blood, has slits at the rotor periphery to take suspension hooks for the bodies containing the sample tubes
EP1663800A2 (en) * 2003-09-22 2006-06-07 Battelle Memorial Institute Press for removing supernatant from a flexible vessel
EP1663800A4 (en) * 2003-09-22 2007-04-25 Battelle Memorial Institute Press for removing supernatant from a flexible vessel
KR101091052B1 (en) * 2009-02-23 2011-12-08 차의과학대학교 산학협력단 Device for centrifugal separation and method using the same
WO2010137884A2 (en) * 2009-05-27 2010-12-02 (주)차바이오메드 Centrifugal separation method, centrifugal separation apparatus, and bag for centrifugal separation
WO2010137884A3 (en) * 2009-05-27 2011-03-10 (주)차바이오메드 Centrifugal separation method, centrifugal separation apparatus, and bag for centrifugal separation
WO2011071353A3 (en) * 2009-12-07 2011-11-10 Jeon Min-Yong Centrifuge tube
WO2011122844A2 (en) * 2010-04-02 2011-10-06 (주)차바이오메드 Bag for centrifugal separation and centrifugal separation method using the bag for centrifugal separation
WO2011122844A3 (en) * 2010-04-02 2012-02-02 (주)차바이오메드 Bag for centrifugal separation and centrifugal separation method using the bag for centrifugal separation
KR101110051B1 (en) * 2010-04-02 2012-02-15 (주)차바이오메드 Bag for centrifugal separation and method of centrifugal separation using bag for centrifugal separation
KR20170002162A (en) * 2015-06-29 2017-01-06 노정자 Kit for separating blood and method for separating blood
KR101726948B1 (en) * 2015-06-29 2017-04-13 노정자 Kit for separating blood and method for separating blood

Also Published As

Publication number Publication date
EP0680311A1 (en) 1995-11-08
SE469211B (en) 1993-06-07
SE9201279L (en) 1993-06-07
SE9201279D0 (en) 1992-04-23

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