EP0168407A4 - Regelung des transmembrandruckes bei der plasmamembranfiltration. - Google Patents

Regelung des transmembrandruckes bei der plasmamembranfiltration.

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Publication number
EP0168407A4
EP0168407A4 EP19840904263 EP84904263A EP0168407A4 EP 0168407 A4 EP0168407 A4 EP 0168407A4 EP 19840904263 EP19840904263 EP 19840904263 EP 84904263 A EP84904263 A EP 84904263A EP 0168407 A4 EP0168407 A4 EP 0168407A4
Authority
EP
European Patent Office
Prior art keywords
plasma
flow path
pressure
filtrate
membrane
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP19840904263
Other languages
English (en)
French (fr)
Other versions
EP0168407A1 (de
Inventor
Arnold C Bilstad
Richard I Brown
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
Original Assignee
Baxter Travenol Laboratories Inc
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 Baxter Travenol Laboratories Inc filed Critical Baxter Travenol Laboratories Inc
Publication of EP0168407A1 publication Critical patent/EP0168407A1/de
Publication of EP0168407A4 publication Critical patent/EP0168407A4/de
Withdrawn legal-status Critical Current

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/22Controlling or regulating
    • 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
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496Plasmapheresis; Leucopheresis; Lymphopheresis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D63/00Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/02Hollow fibre modules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2313/00Details relating to membrane modules or apparatus
    • B01D2313/19Specific flow restrictors

Definitions

  • the present invention relates, in general, 5 to plasma filtration of the type in which a filter membrane is employed for the separation of plasma or plasma proteins from a plasma-containing fluid. More particularly, the present invention relates to method and apparatus for controlling the differential pres-
  • membrane plasma filtration is the separation of plasma from the cellular components of whole blood for collection or replacement.
  • membrane plasmapheresis Another form of membrane plasma filtration is the separation of one or more plasma proteins from the remaining plasma constituents for therapeutic or other purposes. In both types of plasma filtration,
  • 25 plasma is separated from the whole blood by passing the blood along the surface of a filter membrane which has a very small pore size that permits passage of plasma, while retaining the cellular components, i.e., red cells, white cells and platelets.
  • a filter membrane which has a very small pore size that permits passage of plasma, while retaining the cellular components, i.e., red cells, white cells and platelets.
  • the cellular compo ⁇ nents are returned to the donor, and the plasma fil ⁇ trate is collected.
  • the amount of plasma separated from the cellular components of whole blood is related in sub ⁇ stantial part to the driving force or differential pressure between the whole blood side of the membrane and the plasma side of the membrane, i.e., the trans- membrane pressure.
  • the transmembrane pressure actu ⁇ ally preferred for plasmapheresis is sub ⁇ ject to differing views. It has generally been be ⁇ lieved that higher transmembrane pressures will re- suit in a greater amount of plasma being collected from a given quantity of whole blood. See, e.g., U.S. Patents Nos. 4,191,182 to Popovich et al. and 3,705,100 to Blatt et al. In accordance with this understanding, it is desirable to operate, at as high a transmembrane pressure as possible without causing hemolysis (destruction of red blood cells) .
  • transmem ⁇ brane pressure Numerous factors can affect the transmem ⁇ brane pressure. Obviously, and most importantly, the speed of the blood pump which causes the blood to flow across the membrane will directly affect the blood pressure, and thus the transmembrane pressure. The pressure on the plasma side of the membrane also will obviously affect the transmembrane pressure. In routine plasmapheresis processes, the plasma is typi ⁇ cally maintained at atmospheric pressure. Raising or lowering the plasma collection container relative to the filter membrane will, however, cause the plasma pressure, and thus the transmembrane pressure, to vary.
  • blood pressure and transmembrane pressure are affected by other factors associated with the blood flow stream.
  • the size of the needle returning the cellular components (commonly referred to as plasma- poor blood) to the patient can affect transmembrane pressure.
  • a smaller bore needle will increase the pressure on the blood side of the membrane thereby raising the transmembrane pressure.
  • the use of auxiliary equipment in the plasma poor blood return line, such as blood warmers may also increase the transmembrane pressure.
  • donor movement For example, raising or lowering the arm of the donor will cause the transmembrane pres ⁇ sure to vary.
  • transmem ⁇ brane pressure is not the same at different locations along the filter membrane. Because the pressure of plasma separated from the whole blood is typically static, variations in the transmembrane pressure are essentially a function of variations in the pressure of the whole blood. As in any other flowing stream, a natural pressure drop occurs in the whole blood stream as it flows over the membrane. The transmem ⁇ brane pressure is thus greatest at the upstream or inlet end of the membrane, hereinafter referred to as the maximum transmembrane pressure, and continuously decreases as blood flows along the membrane.
  • the maximum transmembrane pressure One device and method for isolating the transmembrane pressure from the effects of downstream occlusions or pressure variations is described in the U.S. Patent No.
  • Such apparatus functions essen ⁇ tially to isolate the membrane from downstream blood flow disturbances, and will not control the transmem ⁇ brane pressure in the event of upstream fluctuations, -5-
  • the present invention is embodied in or employed in con ⁇ nection with membrane plasma filtration apparatus of the type having a filter membrane, one side of which forms a portion of a flow path between a plasma-con ⁇ taining fluid inlet and a fluid outlet, and having a plasma filtrate outlet communicating with the other side of the membrane.
  • the plasma-containing fluid is whole blood and the plasma filtrate is plasma.
  • the plasma-containing fluid may be plasma itself, and the plasma filtrate may be one or more plasma proteins.
  • the maximum transmembrane pressure which may occur is limited to a selected value by control means which is in fluid communication with the plasma-containing fluid flow path at a location upstream of the mem ⁇ brane, and which is cooperatively associated with the plasma filtrate flow path.
  • the control means is dis ⁇ posed or biased by a force of selected amount (cor ⁇ responding to a fluid pressure which will result in the desired maximum transmembrane pressure) to main ⁇ tain the filtrate flow path in a normally open condi ⁇ tion, and is operable when plasma-containing fluid pressure exceeds the desired value to vary the size of the filtrate flow path inversely with respect to the pressure changes in the fluid flow path, so that the maximum differential pressure across the membrane is maintained substantially at the selected value re ⁇ gardless of upstream or downstream changes or fluctu ⁇ ations in the pressure of the fluid flow path.
  • control means includes a movable sur ⁇ face in fluid contact with the fluid flow path and operable to vary the size of the plasma filtrate flow path movement in response to pressure changes in the plasma-containing fluid flow path.
  • a force exerted on the surface biases the surface to a normally open filtrate flow path position.
  • the control means reduces the size of the filtrate flow path, resulting in an increase in filtrate pressure, which keeps the maximum transmembrane pressure con-
  • the bias ⁇ ing force may be selected to correspond to a fluid pressure which will provide a maximum transmembrane pressure at or slightly below that at which he olysis begins, or to provide a substantially lower maximum transmembrane pressure at which it is believed that more efficient plasma collection occurs.
  • the preferred embodiment of the present invention operates to restrict plasma flow only when the upstream blood flow pressure exceeds a desired level represented by the biasing force. So long as the upstream fluid pressure (and thus the transmem ⁇ brane pressure) is less than the selected maximum level, the preferred embodiment of the present inven- tion is quiescent and does not affect the plasma fil ⁇ tration operation.
  • the preferred em ⁇ bodiment of the present invention operates to limit the maximum transmembrane pressure which may occur in the plasma filtration process, and does not preclude operating at a transmembrane pressure lower than the desired maximum.
  • a further alternative embodiment of the present invention includes means for selecting the amount of force biasing the movable surface, thus providing the user with a capability for selecting and changing the desired maximum transmembrane pres ⁇ sure.
  • Figure 1 is a schematic representation of plasmapheresis apparatus and the flow system associ ⁇ ated with a continuous donor procedure, embodying the present invention to control the maximum transmem ⁇ brane pressure.
  • Figure 2 is a schematic representation of a " portion of the system shown in Figure 1, depicting an alternative embodiment of the apparatus for control- ling the maximum transmembrane pressure.
  • Figure 3 is a top view of the apparatus of Figure 5.
  • Figure 4 is a bottom view of the apparatus of Figure 5.
  • Figure 5 is a sectional view taken along line 5-5 of Figure 3, depicting apparatus embodying the present invention for use in controlling the max ⁇ imum transmembrane pressure in plasma filtration pro ⁇ Waits.
  • Figure 6 is a sectional view of alternative apparatus embodying the present invention for controlling the maximum transmembrane pressure in plasma filtration processes.
  • Figure 7 is a partial top view of apparatus of Figure 8.
  • Figure 8 is a sectional view of apparatus embodying the present invention for use in control ⁇ ling maximum transmembrane pressure in plasmapheresis apparatus, and including means for selecting such transmembrane pressure.
  • Figure 9 is a sectional view of apparatus embodying the present invention for controlling maxi ⁇ mum transmembrane pressure in plasmapheresis appara ⁇ tus including means for preventing plasma flow when upstream whole blood pressure is below a selected amount.
  • Figure 10 is a cross-sectional view of yet another alternative embodiment of the present inven ⁇ tion for controlling maximum transmembrane pressure in plasma filtration processes.
  • the present invention is also useful in other plasma filtration ap ⁇ plications where it is desirable to limit the maximum transmembrane pressure.
  • the pre ⁇ sent invention may be generally embodied or employed in connection with plasmapheresis apparatus 12 of the type having at least one filter membrane 14 of suit- able pore size for separating plasma from whole blood as the whole blood flows along the surface thereof.
  • plasmapheresis apparatus 12 of the type having at least one filter membrane 14 of suit- able pore size for separating plasma from whole blood as the whole blood flows along the surface thereof.
  • Figure 1 which depicts a continuous plasmapheresis apparatus and system
  • whole blood from a patient/donor is introduced into an in- let 16 of a filter module or housing 18 containing the filter membrane. In the illustrated embodiment.
  • the membrane 14 is in the form of a hollow fiber through which the blood flows, and a bundle of such fibers extend between the inlet 16 and a housing outlet 20, from which the plasma-poor blood exits.
  • the membranes could be of other suitable shape or configuration without departing from this invention.
  • Plasma removed from the whole blood is collected from a plasma outlet 22 and stored in a suitable container 24.
  • the amount of plasma col ⁇ lected or harvested from the whole blood depends in significant part upon the pressure differential be ⁇ tween the blood side of the filter membrane and the plasma, side of the filter membrane, i.e., the trans- membrane pressure, although there are different views as to which transmembrane pressure is most desirable.
  • the transmembrane pressure and in particular, the maximum transmembrane pressure, is limited to a se- lected vaiue by control means, generally at 26.
  • the control means 26 is in fluid communication, via con ⁇ duit 28, with whole blood flow path 30 upstream of the membrane 14, and is cooperatively associated with the plasma flow path 32 which extends between the plasma outlet 22 and the container 24.
  • the control means 26 is operable to vary the size of the plasma flow path inversely with respect to changes in the whole blood pressure in flow path 30, and is biased toward a normally open flow path position by a force of selected amount representative of the desired blood flow pressure or transmembrane pressure.
  • control means 26 for vary ⁇ ing the size of the plasma flow path includes means defining a movable surface 34 exposed to contact with the blood flow stream.
  • this is conceptually illustrated as the surface of a movable piston 36.
  • the blood and plasma flow path are sepa ⁇ rated by a membrane 38 which coacts with a spring- biased plunger 40 that varies the size of an orifice through which plasma flows.
  • Biasing means in the form of a compressed spring 42 exerts a biasing force against the plunger 40, which force may be fixed as depicted in the embodiment shown in Figures 5 and 6, or adjustable, as depicted in Figures 7 and 8, to permit operator selection of the maximum transmem- brane pressure by the simple rotation of a dial which varies the compression of the spring.
  • backflow prevention means such as the sealing sleeve 44 carried on the plunger 40, is provided to close the plasma flow path completely, in the event that the plasma pressure ex ⁇ ceeds the blood inlet pressure.
  • the sealing sleeve may also operate to block the plasma flow path in the event that the whole blood inlet pressure falls below the selected value corresponding to the maximum transmembrane pressure.
  • this embodi ⁇ ment unlike the other embodiments, would require that the plasmapheresis be conducted at the maximum selected transmembrane pressure.
  • the biasing force as shown in Figure 10, need not be an inwardly direc ⁇ ted force as shown in Figures 1-9, but may be an out- wardly directed.
  • Figure 1 shows a plasmapheresis apparatus and system embodying the present invention for use in continuously collecting or harvesting plasma from the whole blood of a patient or donor.
  • Blood is taken from the patient/donor through a phlebotomy needle or the like, and collected temporarily in a reservoir or chamber (not shown) which communicates with pump 46.
  • the pump is typically a peristaltic type pump which operates by massaging the walls of the flexible plas ⁇ tic tubing through which the blood flows, either by rollers or a series of contacting fingers.
  • peristalic pumps are well known in the medical field and the present invention is not directed or limited to the use any particular type of pump in the plasmapheresis system.
  • the whole blood flows along conduit 30, which is typically a plastic tube, and into the inlet 16 of the filter module or housing 18.
  • the particular filter module shown is generally representative of a plasmapheresis filter commercial ⁇ ly available from the Fenwal Laboratories Division of Travenol Laboratories, Inc. as the Model CPS-10, al ⁇ though other plasmapheresis filter modules could readily be used with the present invention.
  • the fil ⁇ ter membranes 14 are in the form of hollow polypropy ⁇ lene fibers through which the blood flows.
  • the bore of such fibers is typically about 300 microns in dia ⁇ meter, and the walls of the fibers have an average pore size of about 0.3 microns, which permits the passage of plasma through the walls while retaining the cellular components of the blood within the bore of the hollow fiber.
  • a bundle of many hollow fibers is positioned within the housing 18, extending between the inlet 16 and the plasma- poor blood outlet 20.
  • Each end of the bundle of hollow fiber mem ⁇ branes 14 is encapsulated in a liquid-tight polyure- thane potting seal 48.
  • the end seals 48 are spaced slightly from the respective inlet and outlet ends of the module or housing 18 to provide manifold spaces 50 which permit blood to flow into and from all of the fibers in the bundle.
  • plasma filters through the porous walls of the membranes, and collects in chamber 52 within the module between the potted seals 48.
  • Plasma-poor blood exiting from the hollow fibers is removed through the plasma-poor blood outlet 20 of the module.
  • Plasma collected in the chamber 52 between the potted seals 48 may be drained or removed through the plasma outlet 22.
  • the plasma-poor blood is returned to the pati ⁇ ent/donor through conduit 54 and a needle (not shown).
  • auxilary equipment such as blood warmers or the like associated with the 5 plasma-poor blood flow line and there will, of course, be a bubble trap through which the plasma- poor blood must flow before return to the patient.
  • the pres ⁇ sure of the whole blood at the upstream end or inlet of the filter membrane is generally designated as BPi 15 and the pressure of the the plasma-poor blood at the downstream or outlet end of the membrane is desig ⁇ nated as BPg.
  • the plasma collected between the pot ⁇ ted seals 48 has a sufficiently low flow rate that it is essentially static, and thus substantially the 20 same pressure is present throughout the collection chamber 52 and plasma flow path 32. This plasma pressure is referred to, for convenience, as PP.
  • BP**_- 25. BPg the transmembrane pressure
  • BPi-PP the transmembrane pressure
  • BPn-PP the transmembrane pressure
  • hemolysis typically begins to occur when the transmembrane pressure exceeds about 120 mmHg, although the precise point at which hemoly ⁇ sis occurs may vary with different filter modules and different blood flow rates.
  • the transmem- brane pressure at the upstream end of the membrane should not exceed 120 mmHg.
  • the maximum transmem ⁇ brane pressure is controlled at a selected level, which may be the* highest possible pressure without hemolysis or- an optimal pressure for more efficient plasma collection, by providing control means 26 which is in fluid communication with the whole blood flow path 30 upstream of the filter membrane, and is cooperatively associated with the plasma flow path 32.
  • the operation of the control means 26 is figura ⁇ tively illustrated in Figures 1 and 2.
  • the piston 36 is slidably mounted in the chamber of a housing 56, and divides that chamber in- to two subchambers 58 and 60, respectively below and above the piston.
  • Chamber 58 receives whole blood through conduit 28 which communicates with the whole blood flow path 30 at a location upstream of the filter membrane.
  • Plasma from outlet 22 flows through the other chamber 60 of housing 56, and through an aper- ture 62 defined in top wall 64 of the chamber. From the housing, the plasma flow line connects with an appropriate collection container 24.
  • the piston 36 mounts a tapered stem 66 which extends upwardly through the outlet aperture 62, with the space between the stem and the edge of the aperture defining the opening through which plas ⁇ ma must pass. Movement of the piston upwardly re ⁇ considers the size of the opening, and movement downward- ly increases the size of the opening.
  • Biasing means such as the compressed spring 42 or other suitable force generating means is provided for exerting a biasing force of selected amount downwardly on the plunger to maintain the plasma flow path between the stem and the edge of the aperture in a normally open position.
  • the biasing force is preferably pre-selec- ted to provide the desired maximum transmembrane pressure.
  • the piston is forced upwardly, constricting the plasma flow path through the housing 56 and causing a resultant increase in the plasma pressure PP which maintains the maximum transmembrane pressure substantially constant.
  • a subsequent decrease in the whole blood pressure in conduit 30 permits the biasing force to move the piston 36 downwardly, opening the plasma flow path, thereby reducing the plasma pressure and maintaining the transmembrane pressure at or below the desired maximum.
  • the biasing force is thus predetermined so as to correspond to the net force exerted on piston 36 by the blood inlet pressure (BPi) when it reaches the level BPi max at which the desired maximum transmembrane pressure exists.
  • the net force pushing the piston upwardly is simply the quantity (BP ⁇ -PP), which is also the transmembrane pressure, multiplied by the surface .area, of the piston.
  • the biasing force needed may be calculated by multiplying 120 mmHg. by the surface area of the piston 36. It should be noted from this calculation, that for the piston operated control means 26, the pre-selected biasing force remains unchanged regardless of the amount of the plasma pressure (PP) .
  • the present invention operates to limit the maximum transmembrane pressure to that selected regardless of the height of the plasma collection container 24 relative to the filter membrane, thereby eliminating operator error or variance in the positioning of the collection container as a factor affecting the maximum transmembrane pressure which may occur.
  • the whole blood pressure may vary for different reasons. Variation in the up ⁇ stream pump speed will result in different whole blood pressures. Also, upstream or downstream con- strictions to the flow of plasma-poor blood flow path, for example, blood warmers, needles or other auxilary equipment, may also cause a change in the blood flow pressure. Regardless of the reasons for the change in blood flow pressure, and regardless of whether the result of upstream or downstream con ⁇ striction, the control means 26 of the present inven ⁇ tion operates to limit the maximum transmembrane pressure to the selected value represented by the biasing force. For this reason, the .
  • present invention finds particular application in connection with plas ⁇ mapheresis processes which are preferably operated at an optimum transmembrane pressure substantially less than the transmembrane pressure at which hemolysis occurs.
  • it is desir ⁇ able in connection with such a process to maximize the blood flow rate along the membrane.
  • BP- blood inlet pressure
  • BPi max blood inlet pressure
  • flow rates would have to be maintained at less than the prefer ⁇ red highest rate so that the optimal transmembrane pressure (BPi max -PP) is not exceeded.
  • the blood pump speed may be increased to provide as large a blood flow as practical through the module, while apparatus of the present invention limits the maximum transmembrane pressure to that pre-selected value at which most ef ⁇ ficient plasma collection is believed to occur, even though the blood inlet pressure exceedsBPi max .
  • the means 26 for controlling transmembrane pressure in Figure 1 is remote from the whole blood flow path 30, requiring the conduit 28 to communicate between the whole blood line and the subchamber 58 of housing 56.
  • Figure 2 is an alternative schematic presentation of the present invention, in which the blood flows directly through the subchamber 58 up ⁇ stream of the filter membrane. This embodiment re ⁇ symbolizes the potential for stagnant blood which is pos- sible in the remote embodiment depicted in Figure 1. Otherwise, the operation of the control means 26 depicted in Figure 2 is the same as that shown in Figure 1, employing the piston 36 which is movable in the same manner as described earlier to constrict or open the plasma flow path between plasma outlet 22 and the plasma collection container 24.
  • FIGs 3-5 depict a preferred embodiment of the means 26 of the present invention for control ⁇ ling the transmembrane pressure in membrane plasma- pheresis apparatus.
  • the housing 56 is made of two-piece rigid plastic construction, with a bottom portion 68 and a top portion 70 which are preferably joined by solvent or sonic bonding or the like.
  • the housing is generally circular in plan view, although other shapes suitable for high speed plastic molding operations may also be used.
  • the top and bottom portions are appropriately shaped to de ⁇ fine, when joined, a hollow interior chamber, which is divided into two separate subchambers 72 and 74 by the flexible diaphragm 38.
  • the subchamber 72, lo ⁇ cated below the diaphragm, is intended for remote communication with the blood flow path 30 upstream of the filter membrane in the same manner described -lier in connection with Figure 1.
  • a channel 76 is formed diametrically "he bottom portion 68, and has an end aperture 78 communication with the conduit 28 extending between the blood flow path 30 and the housing 56.
  • the top portion 70 of the housing is gener- ally circular for mating connection with the bottom portion 68.
  • the top portion has a generally flat upper wall 80, with an upstanding plasma inlet port
  • a radially • acted plasma outlet 86 communicates through the
  • the diaphragm 38 which divides the housing chamber into subchambers is preferably of flexible, resilient, medically inert material, such as silicone rubber or other suitable material.
  • the diaphragm is generally circular, and includes a thickened rim por ⁇ tion 90 which is captured in an annular slot 92 in the underside of the edge of the top portion. When the top and bottom portions of the housing are assembled, the thickened rim is locked in a liquid-
  • the plunger 40 is mounted for reciprocal movement in the subchamber 74 of the housing.
  • the plunger 40 is pre ⁇ ferably of rigid plastic construction, including a broad flat circular base portion 96, which is sub ⁇ stantially the diameter of the subchamber 74 and rests atop the diaphragm 38, and including an up ⁇ standing stem 98 which extends into the hollow of the center portion 84 of the housing.
  • the upstanding stem 98 has a curved sidewall 100, and an upper reduced diameter portion 102.
  • the flow of plasma through the housing is controlled by reciprocal move ⁇ ment of the plunger 40, which varies the space be ⁇ tween the curved side wall 100 of the stem and the facing inside corner surface 104 of the top portion of the housing.
  • the stem sidewall 100 is spaced from the corner 104 and thus open to plasma flow from the inlet 82 to plasma out ⁇ let aperture 86.
  • the sidewall 100 of the stem 98 and the corner surface 104 of the housing are in contact, completely blocking the flow of plasma through the housing.
  • biasing means 41 may be employed to bias the plunger 40 in a normally opened position.
  • the biasing means is a compressed spring 42 which exerts a downward force on the plunger.
  • the spring 42 extends between a raised locating boss 106 on the top wall of the center por- tion of the housing and a shoulder 108 on the stem 98 formed by the reduced diameter portion 102.
  • the coil spring is selected to exert the desired downward force on the plunger, to maintain the plasma flow path open when the inlet blood pressure BPi is below the amount BPi max required for the desired transmem ⁇ brane pressure.
  • the following examples illustrate biasing force selection for a desired maximum trans ⁇ membrane pressure. For a system where the plasma is maintained at atmospheric pressure (i.e.
  • the maximum blood pressure BPi max which will provide the maximum transmembrane pressure is 880 mmHg.
  • the up ⁇ ward force exerted by this pressure on the plunger 40 is essentially the product of the pressure multipli ⁇ ed by the area of surface 34 of the piston or plunger • ⁇ BP imax x plunger area). Assuming that the surface area 34 is ten (10) square centimeters, the force exerted by the blood flow pressure is calculated as 8800 mmHg cm 2 .
  • a coil spring 42 is the spring constant (K) multipli- ed by the distance of compression. Accordingly, in the present invention, a spring 42 would be selected having the desired constant K so that when mounted in compression in the housing, it would exert a force equal to 1200 mmHg cm 2 on the plunger in the open plasma flow path position. In operation, when inlet blood flow pressure BPi is less than 880 mmHg., the spring will keep the plasma flow path open and the transmembrane pressure will always be less than 120 mmHg.
  • Another example shows that the elevation of the plasma collection container 24 does not affect the biasing force selection for an optimal maximum transmembrane pressure in the preferred embodiment of the present invention. For example, if the plasma collection container is elevated so that the plasma pressure PP is 18 psi or 930 mmHg., and assuming the desired maximum transmembrane pressure is still 120 mmHg., the maximum inlet blood pressure BP max which may occur before exceeding the desired transmembrane pressure is 1050 mmHg. Applied over a plunger area
  • the inlet blood pressure BPi raax exerts an upward force of 10,500 mmHg cm 2 on the plunger.
  • the plasma exerts a downward force on the plunger of 9300 mmHg. cm 2 (930 x 10), leaving a net 5 upward force of 1200 mmHg. cm 2 , the same as with the example above.
  • the pre ⁇ sent invention will provide the desired maximum transmembrane pressure even when the collection con- 10 tainer is below the membrane, in a gravity-assist position.
  • Such positioning of the plasma collection container may be helpful, for example, if patient limitations do not permit a pump speed sufficient to generate the desired blood inlet pressure.
  • the collection bag is sufficiently lower than the membrane that the static plasma pres ⁇ sure PP is 700 mmHg.
  • the in ⁇ let blood pressure BPi max need only be 820 mmHg., as 20 constrasted to 880 mmHg. and 1050 mmHg. in the above examples.
  • the inlet blood pressure BPi max exerts an upward force of 8200 mmHg. cm 2 on the underside of the plunger. Because the plasma pressure PP pushes down on the 25 plunger with a force of (700 mmHg. x 10 cm 2 ) 7000 mmHg. cm 2 , the resultant upward force on the plunger is 1200 mmHg. cm 2 , the same as with the other examples. Thus, the selected biasing force need not be changed, and the maximum pressure is still limited 30 to the desired value, even when the plasma collection is in a gravity-assist position.
  • the plunger 40 is biased downwardly by the coil spring 42, maintaining the plasma flow path in a nor- mally open position.
  • the force exerted on the plunger from the underside of the diaphragm 38 pushes the plunger up- wardly, reducing the size of the plasma flow path between the plunger stem and the housing wall, and causing an increase in the plasma pressure to offset the increase in the blood inlet pressure.
  • the plunger moves downwardly by the spring force-, further opening the flow path and allowing a greater flow of plasma" with a resultant lower pressure of plasma.
  • FIG. 6 An alternative embodiment of the transmera- brane pressure control means 26 of the present inven ⁇ tion is depicted in Figure 6. That apparatus is con ⁇ structed essentially the same as the one described in Figures 3-5, except that the subchamber 72 forms a portion of the whole blood flow path upstream of the filter membrane 14 in a manner similar to that dia- grammatically shown in Figure 2. To achieve this, the chamber 74 has a whole blood inlet 110 and an outlet 112 which permits blood flow through the cham ⁇ ber, instead of the remote arrangement to which Figure 5 is directed. Otherwise, the operation of the apparatus depicted in Figure 6 is identical to
  • Figures 7 and 8 depict another embodiment of the control apparatus shown in Figure 5, which permits the operator to adjust the biasing force and thereby select the preferred maximum transmembrane pressure.
  • Many of the features of the apparatus de ⁇ picted in Figure 8 are the same as shown in Figure 5, and the description will not be repeated.
  • the essen ⁇ tial difference between Figure 8 and Figure 5 is that the top wall of the upstanding center portion 82 in Figure 5 has been replaced by a rotary cap or dial 114 threadedly attached to the wall of the center portion. Rotation of the cap clockwise (Fig.
  • the cap bears indicia of the pressure that is being selected.
  • the cap is calibrated for maximum transmembrane pressure, and bears numbers and raised ribs 116 indicating a maximum transmembrane pressure between 50 and 120 mmHg.
  • the raised ribs 116 and numerals may be aligned with rib 118 on the plasma outlet for selection of that particular trans- membrane pressure.
  • the preferred maximum transmembrane pressure is 110 mmHg.
  • he or she may turn the dial until the number 110 and its reference mark is aligned with the raised rib 118 on the plasma outlet.
  • a coil spring is 5 selected which has a spring constant so that when compressed in the amount resulting from rotation of the cap, it will exert a downward biasing force on the plunger which is only overcome when the blood inlet pressure exceeds the value BP max which pro-
  • the dial may also have indicia representative of different commercially available filter modules, each indicia being repre ⁇ sentative of the transmembrane pressure preferred for
  • the dial 114 may have indicia representing an adjustment preferred after a period of operation to compensate for filter clogging or coating which, if uncompensated for, will decrease
  • Figure 9 depicts yet a further alternative apparatus embodying the present invention for preven ⁇ ting the backflow of plasma when the plasma pressure (PP) exceeds the blood inlet pressure (BPi).
  • the embodiment in Figure 9 may actually oper- ate in a substantially different mode from the other embodiments of the present invention.
  • the biasing force is illustrated generally, rather than particularly, and the upstanding -center portion 84 of the housing is open at the top.
  • the embodiment in Figure 9 incorporates a back flow prevention means in the form of a sleeve 44 associated with the stem 98 of the plunger 40.
  • the sealing sleeve is of pre ⁇ ferably resilient elastometric material such as sili- cone rubber or similar material.
  • the sealing sleeve is mounted over the reduced diameter portion 102 of the stem 98, and may further be sealed to the stem by solvent or the like to prevent the escape of liquid.
  • the upper end of the seal comprises a larger dia- meter skirt or bellows portion 120, which terminates in a thickened rim 122.
  • the thickened rim is cap ⁇ tured between a locking ring 124 and the top edge of the upstanding center portion 84.
  • the locking ring 124 has a depending internal peripheral lip 126 which forms an undercut in the ring 124 that receives the thickened rim 122 in fluid-tight engagment.
  • a radially extending sealing flange 128, which is wider than the opening 130 in the top portion of the housing, through which the stem 98 extends.
  • the sleeve 44 is positioned on the stem 98, so that when the plunger 40 is raised, the radial flange 128 is lifted from shoulder 132 surrounding opening 130, permitting plasma to flow from the inlet 82 to the outlet 86.
  • the bellows portion of the seal permits reciprocal movement of the plunger while also sealing the open upper end of the upstanding portion 84 of the housing.
  • the force exerted by the plasma will push plunger 40 completely down ⁇ wardly until the sealing flange 128 closes against the annular shoulder 132 surrounding aperture 130, thus preventing back flow of plasma toward the filter membrane.
  • This may occur, for example, when plasma is being collected in a suspended container and there is a gravity pressure head.
  • the gravity head may tend to create a reverse flow of plasma back through the membrane and into the blood flow path.
  • the backflow prevention valve of the present invention prevents this from occurring.
  • the sleeve 44 is positioned on stem 98 to block the plasma flow path when the down ⁇ ward biasing force 41 is greater than the force exerted by the inlet blood pressure.
  • the desired maximum value BPi max to achieve the desired transmem ⁇ brane pressure.
  • Figure 10 shows apparatus of the present invention wherein the biasing force is exerted in a different direction than shown in the preferred embodiment.
  • Figure 10 shows control means 26 in which the housing 54 has a flexible upper portion 134 and a lower portion 136, peripherally sealed together to define an interior chamber.
  • a flexible diaphragm or membrane 138 which is peripherally sealed between the housing portions, divides the interior chamber into the subchambers 140 and 142.
  • Plasma flows into the device through inlet 144.
  • a plasma outlet 146 is defined by a grommet 148 in the center of the lower portion 136.
  • the member 150 has a generally flat top surface 152 which directly underlies the membrane 138, and a depending center cylindrical portion 154 which is movable into and away from contact with the grommet 148.
  • Means for exerting a biasing force on the member 150 is provided in the form of a connecting member 156 which extends through the flexible upper housing portion 134 and through the diaphragm 138, and is fixedly attached within the center cylinderi- cal portion 154 of member 150.
  • OMPI member normally maintains the center cylindrical por ⁇ tion 154 in a spaced-apart relationship with the grommet 148 at the plasma outlet, providing a plasma flow path through the housing in a normally open con- dition.
  • Blood from the blood flow line 30 upstream of the filter membrane communicates with the upper chamber 140 via condui ' t 28, and exerts a downward pressure on the diaphragm 138 and member 150.
  • the force of the whole blood pressure on the member 150 exceeds the selected biasing force, it pushes the member toward the outlet grommet 144, reducing the space between the grommet and the cylindrical portion 154 of the member, thereby reducing the plasma flow rate and increasing the plasma pressure to maintain the transmembrane pressure of the filter module substantially constant.
  • the biasing force tends to open the plasma flow path, resulting in lower plasma flow pressure.
  • the present invention provides new and unique means and method for controlling the transmembrane pressure in membrane plasma filtration apparatus and systems, regardless of whether pressure variations in the plasma-containing fluid flow line occur upstream or downstream of the filter membrane.
EP19840904263 1983-12-09 1984-11-05 Regelung des transmembrandruckes bei der plasmamembranfiltration. Withdrawn EP0168407A4 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56006083A 1983-12-09 1983-12-09
US560060 2000-04-27

Publications (2)

Publication Number Publication Date
EP0168407A1 EP0168407A1 (de) 1986-01-22
EP0168407A4 true EP0168407A4 (de) 1987-04-29

Family

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Application Number Title Priority Date Filing Date
EP19840904263 Withdrawn EP0168407A4 (de) 1983-12-09 1984-11-05 Regelung des transmembrandruckes bei der plasmamembranfiltration.

Country Status (4)

Country Link
EP (1) EP0168407A4 (de)
JP (1) JPS61500590A (de)
IT (1) IT1178737B (de)
WO (1) WO1985002554A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4789482A (en) * 1986-02-10 1988-12-06 Millipore Corporation Method for separating liquid compositions on the basis of molecular weight
US6241947B1 (en) * 1998-01-27 2001-06-05 Fuji Photo Film Co., Ltd. Chemical analysis system and blood filtering unit
CA2614676C (en) 2005-07-12 2014-02-25 Zenon Technology Partnership Process control for an immersed membrane system

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3006455A1 (de) * 1980-02-05 1981-08-13 Takeda Chemical Industries, Ltd., Osaka Verfahren und vorrichtung zur niederdruck-filtration von plasma aus blut
EP0096973A1 (de) * 1982-05-28 1983-12-28 Kuraray Co., Ltd. Einrichtung zur Abtrennung von Plasma

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1524217A (en) * 1923-02-05 1925-01-27 American Cellulose And Chemica Regulating valve for artificial-silk spinning apparatus
US4412553A (en) * 1981-06-25 1983-11-01 Baxter Travenol Laboratories, Inc. Device to control the transmembrane pressure in a plasmapheresis system
US4431019A (en) * 1981-06-25 1984-02-14 Baxter Travenol Laboratories, Inc. Fluid flow control device

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3006455A1 (de) * 1980-02-05 1981-08-13 Takeda Chemical Industries, Ltd., Osaka Verfahren und vorrichtung zur niederdruck-filtration von plasma aus blut
EP0096973A1 (de) * 1982-05-28 1983-12-28 Kuraray Co., Ltd. Einrichtung zur Abtrennung von Plasma

Also Published As

Publication number Publication date
JPS61500590A (ja) 1986-04-03
EP0168407A1 (de) 1986-01-22
WO1985002554A1 (en) 1985-06-20
IT1178737B (it) 1987-09-16
IT8423952A0 (it) 1984-12-06

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