DE2308485A1 - DEVICE FOR SEPARATING LIQUID MIXTURES, IN PARTICULAR BLOOD, INTO ITS COMPONENTS - Google Patents

Description

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Becton, Dickinson and Company, East Rutherford, N.J.,

B 715

UNITED STATES.

Device for separating liquid mixtures, especially blood, into its constituent parts

It is known to separate blood into its component parts by centrifugation using a sealed container. Such a container is described, for example, in US Pat. No. 2,460,641. This container is provided at its open end with a lid that can be pierced by a pointed cannula through which the blood enters the container. The clinical Laboratories use this device to take a blood sample into a light phase, i.e. in the serum or plasma, and into a heavy phase, i.e. those contained in the blood Cells, separate. The light phase is then separated from the heavy phase, for example by means of a syringe or removed with a pipette.

Another device for separating the blood constituents is described in U.S. Patent No. 3,508,653. This device is an independent unit, closed by a stopper, for separating body fluid, for example Blood, with a deformable piston initially located in the container near the stopper. After the The container is filled with blood, the device is centrifuged and the blood is divided into its light and heavy weight

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Phase separated. Then there is an increased centrifugal force on the Applied container, the seal between the inner surface of the container and the piston being broken and the Piston is deformed and moves downward through the light phase, with the light phase exclusively between the outer surface of the piston and the inner surface of the container rises. When the piston is the interface between the light and heavy phases reached, the movement of the piston is stopped, the centrifugal force is terminated and the seal between the inner surface of the container and the resilient piston restored to create a barrier between the two Phases to achieve. Other devices for separating the blood into its components are mostly filters, such as in U.S. Patents 3,481,477 and 3 512 94O.

The invention is based on the object of an independent Device for separating liquid mixtures, in particular blood, into their constituent parts To create specific gravity and to provide a tight barrier between them without opening the container or the separated light phase has to be removed from the heavy phase.

It is an object of the present invention to be automatic To break down blood into its components by subjecting the independent unit to a centrifugal force, so that at the end of the centrifugation an impermeable barrier separates the light phase from the heavy phase. The inventive device is capable of a to withstand rough handling during shipment

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Inverting the container without remixing the separated phases allows and various chemical constituents the easy phase from getting back into the heavy phase and mixing with it or vice versa. It is also an object of the invention to provide such a device that allows ixi communication with others Equipment for the removal of items to be centrifuged Blood samples can be used without additional special equipment is * Another object of the invention is to provide an independent unit for separating blood into its components create which is inexpensive to manufacture, easy to assemble and use.

The device according to the invention for separating blood into its components, namely the light phase consisting of plasma or serum and the one consisting of cells heavy phase, is a self-contained unit that has a container with at least one open end, through which a sample of the blood to be separated is introduced. This open end is with a sealing closure provided, which consists of a self-sealing elastoroeren There is material that can be pierced by a pointed cannula. A piston is displaceable in the container arranged, the outer surface of which is in sealing contact with the inner surface of the container. The piston has a pressure responsive valve, which is normally is closed when there is a small pressure difference between the two sides of the piston. That However, the valve opens automatically in the event of a significant pressure difference. Venn the container initially temperate When exposed to centrifugal forces, the blood gets into his light and its heavy phase separately, and if

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then the force is increased significantly, the valve will auto automatically opened, with the light phase through the opened Valve can flow through while the piston is moved down through the light phase, wherein it maintains its seal with the inner surface of the container. A stop is provided on the container, which arranged at a predetermined distance from the bottom of the container which is removed from the initial position of the piston. The piston rests against this stop when he has moved through the easy phase, where the pressure difference. is canceled and the valve automatically goes back from the open to the closed position, to create an impermeable barrier between the light phase and the heavy phase of the blood. Thereafter the centrifugation process is aborted and the sample is separated into phases. for the subsequent investigation ready.

Further details and features of the invention result from the following description in conjunction with the drawings, in which, preferred exemplary embodiments of the Invention are shown. It shows:

Fig. 1 is a longitudinal section through an inventive Centrifuge container in which blood is separated into its light by means of a pointed cannula and heavy phase is introduced,

Fig. 2 is a section similar to Fig. 1 showing the separation of the blood shows the light and heavy phase, with the piston resting against the stop,

3 shows a view of the container according to FIG. 1 from above,

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4 shows a section along line 4-4 in FIG. 2, and

Fig. 5 is a partial section of the container of Fig. 1 with a modified piston, which has a filter insert.

Refer first to Figures 1 through 4, in which a device 10 is shown which has a tubular container 12, both ends 11 and 15 of which are open and closed by plugs 14 and 16. The plugs 14 and 16 consist of a self-sealing one elastomeric material such as rubber. The stopper 16 can be pierced by a cannula 18 through which blood can be introduced into the container 12. Venn When the cannula is removed, the piercing opening in the stopper 16 closes due to the elastomeric property the same by itself, so that no blood can escape.

The plug i4 had a cylindrical shoulder 20 and one flange-shaped head 22 integral therewith has an outside diameter slightly larger than the inside diameter of the container 12, so that the stopper 14 reliably seals the end 11 of the container 12. Of the Head 22 has the shape of a hexagon (see Fig. 3) and has a slightly larger diameter than the cylindrical one Section 20 in order to ensure that the container can be put down without the risk of rolling away. The stopper has a cylindrical portion 28 and an integral cylindrical head 30 with an axial recess 24 ·. The cylindrical section 28 is provided with an annular recess 29 to provide a self-sealing, to form penetrable zone 31, which can be pierced by the cannula 18 with little effort,

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without affecting the seal. As mentioned above, the plugs 14 and 16 are inserted into the ends 11 and 15 of the container 12 is pressed in to seal these ends in a gas-tight manner.

The tubular container 12 is preferably made of glass, although other suitable materials could be used. Between the ends 11 and 15 of the container 12 there is an annular groove 32 which forms a stop 3k on the inner surface of the container. When the piston 4O moves from its starting position shown in FIG. 1 after the separation of the light phase from the heavy phase (see FIG. 2), it rests against the stop 34. If the piston has a greater density than the blood, it is not necessary to take special precautions with regard to the density of the piston relative to the density of the blood, since the piston automatically comes to rest at the stop 34 when the increased centrifugal force exerted on the container will. The sealing of the KojLbens against the inner surface of the container remains from its starting position according to Flg. 1 maintained up to its end position according to FIG.

The piston kO contains a tubular metal insert 52 which is arranged in an annular recess 5k of the piston 40. The insert 52 is preferably made of stainless steel or other rigid, chemically inert material having a density considerably greater than that of blood. The piston kO itself consists of an elastomeric material. The annular recess 54 is dimensioned to receive the tubular insert 52 with an interference fit so that no air space remains in the annular recess 54. '

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The elastomeric area of the piston 4o has an outer wall 48 and an inner wall 46 which delimit the annular recess 5 ^ between them. One-piece rait the outer wall 48 are parallel, resilient sealing rings 50, the abut against the inner wall 13 of the container 12 in a sealing manner. If you work at increased speed during the centrifugation process, the piston 40 is exposed to centrifugal forces which move it downwards. These Movement creates a pressure differential on the two sides of the bottom or diaphragm portion 44 of the piston 40. The membrane 44 is made of a relatively thin, stretchable or resilient material and, in the initial position of the piston according to FIG. 1, lies opposite the stopper 14. The membrane 44 has a number of normally closed openings or perforations 42. The inner wall 46 of the piston 40 encloses a cylindrical space 80 in which the light phase of the blood with increased centrifugal force penetrates. Since the centrifugal force acting on the piston 40 is greater than the force of the light phase is applied to the membrane 44, the punctures open 42 automatically and allow the light phase to pass up through these punctures, wqthrough the piston 40 from its starting position according to FIG. 1 in can reach its end position according to FIG. 2 without its sealing contact with the inner wall 13 of the container 12 is repealed. When the piston 40 is against the stop 34 comes to rest, the pressure difference on the two sides of the membrane 44 is essentially canceled and the Openings or punctures 42 acting as valves close automatically even if the container continues is exposed to centrifugal force.

The tubular insert 52 takes the radially outwardly acting Compressive forces caused by the pressure of the liquid

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are exerted in the cylindrical space 80 during the centrifugation process, so that these forces are kept away from the flexible sealing rings 50 and prevents increased friction between the piston kO and the inner wall 13 of the glass container 12, which impair the displacement of the piston kO or occur would prevent. The rohrförinige insert 52 has, as mentioned, along with de ta elastomeric piston has a density which is greater _Λ than that of blood and caused when it is exposed to a centrifugal force, a downwardly directed thrust which is more than sufficient to provide the Overcome friction of the multiple sealing rings 50 on the inner wall 13 of the container and open the valve openings 42. The elastomeric part of the piston 40 is preferably made of rubber

In Fig. 2, the piston 4θ has its way inside the container 12 ends and it rests against the stop 34. The valve openings 42 are closed. Part of the easy Phase remains above the heavy one separated from it Phase.

In Fig. 4 is a plan view of the piston 40 is shown, when this is in its end position according to FIG. the Resilient sealing rings 50 are in sealing contact with the inner wall 13 of the container 12. In the middle The area of the piston 4θ are the openings 42 in the membrane 44 closed, although the centrifugation process has not yet ended.

In the embodiment of FIG. 5, the piston is 4θ provided with a filter insert 6o, which is in the cylindrical Space 80 is arranged. In every other way

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For example, the container 12, the stopper 1V and the piston are identical to that of Fig. 1 and all corresponding parts are provided with the same reference numerals. The filter 60 can be made of any suitable filter material that is chemically inert to blood and capable of filtering serum or plasma. Such a material can be asbestos or glass wool, a plastic foam with open pores, paper or another fibrous or lumpy material. The main purpose of the filter 60 is to prevent fibrin or partially formed fibrin material from flowing through the valve openings kZ.

To use the device according to the invention, the container is preferably evacuated so that when the cannula 18 is inserted, the container 12 is filled with blood without the need for venting. It is also contemplated that this device of the present invention could be used with the blood collection device disclosed in U.S. Patents 2,460,6kl, 3k69,572 and 3k9k352 . It is important that when the container 12 is filled, the blood is introduced through the stopper 16 at the bottom of the container in order to eliminate the possibility of blood cells becoming trapped between the piston kO and the stopper 14 and the light phase that may be in the Space between these two parts collects, pollute. When the vessel 12 is evacuated, it is clear that the blood fills the space between the stopper 16 and the piston kO.

After the cannula 18 has been pulled out and the container 12 has been filled with blood, it is inserted into a centrifuge with the aid of the recesses 2k and 2k * and the light phase of the blood is first separated from the heavy phase of the blood by using moderate centrifugal force, which

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ben 4θ has not moved from its starting position. The blood cells collect in the container 12 below the stop 34. The rotational speed of the centrifuge is then increased, as a result of which a considerable, downwardly directed thrust is exerted on the piston 4θ. As the piston 4θ begins to move, it increases the hydrostatic pressure in the liquid in front of it, stretching the diaphragm 44 and automatically opening the valve ports 42 so that the piston moves down through the light phase passed through the Valve openings 42 flows upwards. The flask 4O remains in its movement in sealing contact with the inner wall 13 of the container 12. The movement of the piston is completed when this abuts against the stop 34, whereby the pressure ^s difference between the two sides of the membrane hk largely eliminated, and the valve openings close automatically due to the flexibility of the material, even if the container 12 is still under the action of centrifugal forces. Before the centrifugation process is finished, the membrane 44 forms an impermeable partition between the light and heavy phases of the blood.

The centrifuge is now stopped and the phased blood sample is ready for further treatment. Depending on the need, the serum or plasma can end up and / or the concentrated red blood cells removed from the other end of the container.

- patent claims -

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Claims (18)

aSssasssssssassssssssssssssss Device for separating a liquid mixture into light and heavy phases, in particular for separating blood into its light phase consisting of plasma or serum and its heavy phase consisting of cells, preferably by centrifugal force, ge ken _N ζ eicu η et by a Container (12) for receiving the liquid with at least one open end (i5) t which can be closed by a stopper (i6), a piston (4o) which is arranged displaceably in the container (12) and whose density is relatively greater than the heavy phase and which has sealing means (50) on its outer surface for sealing cooperation with the inner wall (13) of the container (12). Means for moving the piston in the vessel to separate a substantial portion of the light phase from the heavy phase, pressure responsive valve means (42) in the piston (4o) which are normally closed, however, at a predetermined pressure when the j The piston moves, opens and closes automatically j essen when the piston comes to a standstill, and a j Stop (34) in the container (12) for the piston (4θ) on the End of his path that separates the easy from the difficult phase. j 2. Device according to claim 1, characterized in that the closure (i6) ajjsj an elastomeric material and can be pierced by a cannula. 3 · Device according to claim 1 and 2, characterized in that that the piston (4θ) is initially near the end of the 309846/0331 The container (12) is arranged opposite the end with the closure which can be pierced by the cannula, and with moderate centrifugal forces, where a separation the light phase takes place from the heavy phase, remains in this position and with higher centrifugal forces is moved through the light phase and in its end position an impenetrable partition between the light and the heavy phase " 4. Device according to one of the preceding claims, characterized in that the piston (4o) consists of one outer body made of elastomeric material and a rigid, tubular insert (52) is made in a corresponding annular recess (5 * 0 in the elaetomer Body is inserted. 5. Apparatus according to claim 4, characterized in that that the insert (52) is arranged with a press fit without air space in the recess (5 * 0. 6. Device according to one or more of the preceding Claims, characterized in that the elastomeric body of the piston (4o) is tubular and at one end is closed by a membrane (44), which is normally closed openings (42) aüfwe. is, which open automatically when there is a predetermined pressure difference exists between the two sides of the membrane (44). * 7 · Device according to one or more of the ViOx-based ones Claims, characterized in that the piston (4o) with einoB! Filter (60) is provided, the undesirable Retains substances in the light phase. - 3 309846/0331 8. Apparatus according to claim 7 * characterized «that * the filter (6o) is arranged in a cylindrical recess (80) in the piston (ko) . 9. Device according to one or more of the preceding claims, characterized in that the stop for the piston (ko) is formed by an annular bead (3 * 0, which represents an annular narrowing of the inner surface (i3) of the container (12). 10. The device according to claim 1, characterized in that that the liquid to be separated is blood and that the piston has a density greater than that is of blood. 11. Flask for separating a liquid mixture into one light phase and a heavy phase in an independent liquid separation device, geke η η - characterized by a body with sealing means (50) on its outer wall. for tight cooperation with the inner wall (13) of the device, a rigid tubular insert (52), the press fit in the Piston body is inserted, and pressure-responsive valve means (42) on the piston (4o), which are normally closed when a slight pressure differential across the Valve means is present and which open automatically at a considerable pressure drop, so that if the device is exposed to moderate centrifugal forces, the liquid in its light phase and its heavy phase Phase is decomposed, and when the device is exposed to increased centrifugal force, the valve means automatically be opened, the easily ^ -phaee flowing through the valve means and the piston down through the 309846/0 331 -4k - light phase can be moved through without the seal of the piston (ho) against the inner surface (13) of the device being broken « 12. Piston according to claim 11, characterized in that it has an axial recess (80) whose end of a wall (44) which contains the pressure-responsive valve means (42). 13 · Piston according to claim 12, characterized in that the wall (44) is made of an elastomeric material, and at least one opening (42) which opens at a low pressure difference between the two sides of the Wall (44) is normally closed and automatically opens when there is a greater pressure difference. 14. Piston according to claim 11, characterized in that the rigid tubular insert (52) made of stainless steel Steel is made. 15 «piston according to claim 11, characterized in that the rigid tubular insert (52) together with the Piston body has a density that is greater than the heavy phase of blood. 16. Piston according to claim 11, characterized in that he filter medium (6o) contains the before. responsive to pressure Valve means (42) are arranged to fixed Hold particles in the light phase as the piston calibrates down through the light phase " moved through. 17. Piston according to claim 16, characterized in that it has an axial recess (80) in which the filter means (60) are arranged. 309846/0331 " ⁵ " 18. Method of sealed separation of blood into his light phase from serum or plasma and its heavy phase from cells by means of a sealed container, I mark η e t by the fact that blood is inserted into the container through a self-sealing lid which is attached to one end of the device, the one of which is sealingly displaceable in the container Piston removed, the piston having pressure responsive valve means and above of the blood to be separated is arranged that the device successively centrifugal forces of different Size is exposed, whereby with moderate centrifugal forces the separation of the blood into its light and its heavy phase takes place, and the piston remains in its starting position with the valve means closed, and then automatically open the valve means and the piston through the light phase is moved therethrough while the light phase flows up through the valve means, and that the flask at a point above the severed heavy phase is halted and the pressure responsive valve means automatically from the open position be brought to the closed position while the centrifugal force continues to act on the container. 19 · Method of separating blood in its light, from Serum or plasma consisting phase and its heavy phase consisting of concentrated red blood cells, characterized in that the blood sample in a sealed and evacuated container is introduced, which is sealed at both ends by elastomeric plugs has a closed pipe and a - 6 309846/0331 contains sliding piston that is in its starting position is arranged near the stopper, which is the stopper opposite, through which the blood is introduced, that the container is first centrifuged at moderate speed, the end of the container adjacent to the piston being on top, so that the piston does not slide down, but the heavy phase of the blood settles on the bottom and the light phase of the blood concentrates over it, whereupon the blood container centrifuges at a considerably increased speed becomes, whereby the sliding piston, the density of which is considerably greater than that of the light or heavy phase of the blood that overcomes tight friction and moves downward, creating the hydrostatic Pressure on the liquid in front of it increases and this increased pressure automatically opens normally closed valve means in the piston, whereby the light phase up through the valve means flows and the piston moves down to a mechanical stop, which a further movement the piston thrust prevented continued centrifugal force, with the light phase of the liquid continuing after flows up through the valve means, whereby the hydrostatic Pressure in front of the piston is reduced until the pressure difference on both sides of the piston so has become small that the valve means automatically close and a permanent impenetrable partition between the light phase and the heavy Phase of blood form. 309846/0331