AU621590B2 - Plasmapheresis filter flow control system - Google Patents

Description

Signature.

ohn F. Gaither, Jr., Secretary THE COMMISSIONER OF PATENTS.

I w I -r r r M rI tj 7 J 1 'j yr"i~iYli~S~'" "~ieuP1''1----xr i OPI DATE 25/08/89 APPLN. ID 30569 89 :i PCT w AOJP DATE 28/09/89 PCT NUMBER PCT/US89/00412 INTERNATIONAL APPLICATION PU I6 2 UNE5 E E E OOPERATION TREATY (PCT) (51) International Patent Classification 4 International Publication Number: WO 89/ 07002 B01D 13/00 Al (43) Interhntional Publication Date: 10 August 1989 (10,08.89) (21) International Application Number: PCT/US89/00412 (81) Designated States: AT (European patent), AU, BE (European patent), CH (European patent), DE (Euro- (22) International Filing Date: 2 February 1989 (02,02.89) pean patent), FR (European patent), GB (European patent), IT (European patent), JP, LU (European patent), NL (European patent), SE (European patent).

(31) Priority Application Number: 152,523 (32) Priority Date: 5 February 1988 (05,02.88) Published With international search report.

(33) Priority Country US (71) Applicant: BAXTER INTERNATIONAL INC. [US/ One Baxter Parkway, Deerfield, IL 60015 (US).

(72) Inventor: PRINCE, Paul, R, 26902 Via la Mirada, San Juan Capristano, CA 92675 (US), (74) Agents: PRICE, Bradford, L, et al,; One Baxter Parkway, Deerfield, IL 60015 (US), (54) Title; PLASMAPHERESIS FILTER FLOW CONTROL SYSTEM (57) Abstract The efficiency of a blood plasmapheresls filter (12) is purposefully reduced at low Input blood flow rates so as to prevent possibly excessive heniatocrit which may make it difficult or impossible to handle the resulting blood cell concen, trate for Infusion purposes) and/or which may cause accompanying red cell damage, Where filter (40) efficiency is a function of rpm of a spinning element such controlled reduction may be achieved by simply controlling spinner rpm as a function linear over at least some range) of the input blood fnw rate,

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1 rr L c. -1 -1- This invention relates to the control of the efficiency of fluid filtering systems and more particularly to optimum control of fluid filtering systems used, for example, to filter blood, blood products or components or other biological fluids such as, for example, in a phasmapheresis system.

This invention is related to commonly assigned, allowed U.S. Patent Application No. 671,576 filed November, 15 i984 (also published under International Publication No. WO 10 86/02858), the entire content of which is hereby incorporated by reference. In particular, although the present invention e may find utility alone, it is particularly suited as an improvement in the adaptive filter concentrate flow control system and method of this related commonly assigned earlier 15 application.

In this related prior adaptive filter control system, a i transmembrane pressure (TMP) operating point is established on anempirically

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WO 89/07002 PCT/US89/00412 -2constructed control curve of TMP versus filtrate flow rate so as to automatically maintain substantially maximum filtrate flow rate for any given operating conditions without permitting the TMP to exceed a threshold value at which irreversible filter clogging (and/or hemolysis) begins to occur. For a detailed description of such prior TMP control system, reference should be made to the above cited related publication. However, it will be appreciated that such prior control systems have typically attempted to maximize the efficiency with which the filter operates to perform desirable separation of filtrate from input fluid (while thereby providing a concentrate output as well). For example, in filter systems employing a rotating spinner, the filter efficiency generally increases as the spinner rpm increases and, accordingly, prior control systems have typically operated the spinner at a constant speed chosen to be substantially the highest acceptable speed the highest speed that can be used without producing undue hemolysis or other adverse effects).

However, I have now recognized that filter efficiency volume of filtrate removed per unit volume of input fluid) can, in some systems, actually become excessive, For example, such filter efficiency is also a function of other parameters fluid residence time within the filter) and where some of these other parameters might vary WO 89/07002 PCT/US89/00412 -3as the input blood flow rate and hence residence time does in a typical plasmapheresis system), it is possible that the efficiency of the filtering elements occasionally may be so high that the concentrate output from the filter becomes excessively thick. For example, in a plasmapheresis system, the hematocrit of cell concentrate may become so high that the concentrate becomes sufficiently viscous as to lose some of its fluid-like characteristics and begin to perform somewhat as a soft solid. Since cell concentrates are typically collected from a patient or other donor and periodically reinfused into that donor, this can cause problems in handling the reinfusing process (which, in turn, may cause undue hemolysis of living blood cells included in that concentrate).

In short, in a plasmapheresis system where plasma is separated from whole blood, the separation efficiency of the filter may become so high that the resulting concentrated red cells become excessively concentrated and very difficult to reinfuse into the donor through practical needle sizes in practical times and through practical blood pumps and may become hemolyzed in the process, another detrimental effect, There may be other fluid filtering and/or processing systems where an input fluid flow rate (or other parameter) might vary so as to sometimes produce such high filtering efficiency that, for some particular applications, it would be preferable to

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have a lower filtration efficiency. Such problems typically may be encountered more frequently (or be of a more critical nature) where living biological fluids are involved in the filtration process.

In particular, I have now recognized that under low blood flow input rates to a plasmapheresis system, it is possible for filter efficiency to be excessive such that the concentrate output from the filter is difficult to handle as a fluid and iay become hemolyzed if forced at high 10 flow rates through needles and blood pumps).

SI have now discovered that these problems can be substantially alleviated by purposefully reducing filter efficiency at lower input fluid flow to the filter.

S: According to one aspect of the invention there is S 15 provided a fluid filtering system comprising a fluid filter having controllable efficiency in separating a filtrate from San input fluid flow and providing a concentrate output fluid flow; and control means connected to controllably decrease filter efficiency sufficiently to prevent excessive concentration of the concentrate output.

According to anothr aspect of the invention there is a Sblood plashapheresis ystem comprising a spinning filter element to separate plasma from blood thereby producing blood cell concentrate and to control operating transmembrane pressure to approximately maximize filtrate plasma flow without irreverisible filter clogging, and, speed control rE_ 't 4a means for controllably changing the rotational speed of said spinning filter element as a function of a predetermined operating parameter of the plasmapheresis system to prevent excessive hematocrit of said blood cell concentrate.

For example, the adaptive filter flow control system of the above referenced related application No. 671,576 (based upon TMP optimization to provide maximum plasma yield) can continue to be used while simply inducing lower efficiencies in the filter device for lower input blood flow rates. Lower input blood flow rates may be encountered, for i* example, where a patient/donor is in poor health and undergoing therapeutic procedures. Inherently poor circulation in the body may well dictate lower blooda .e

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WO 89/07002 PCT/U 89/00412 11 flow rates input to an attached filtration system.

And even some healthy patients forget or refuse to exercise their fist and forearm muscles to increase blood flow rates. As will be appreciated, there are a variety of circumstances where operation at reduced input blood flow rates might be desirable.

Such reduced efficiency inherently removes less plasma at lower blood flow rates and thereby decreases the hematocrit of the concentrate as compared to what it would have been using a higher efficiency filtration process). It would seem that a disadvantage of this system would be reduced plasma and resultant longer procedure times. However, with careful selection of efficiency reduction as a function of input blood flow rates, the ultimate result is improved performance in terms of lowered hemolysis, minor reductions in plasma flow rate and lower minimum blood flow rates for satisfactory plasma separation than available without this feature.

Accordingly, the same filtration system can be used over a wider range of input blood flow conditions without encountering adverse effects such as those mentioned above. In the preferred exemplary embodiment, the fluid filter uses a spinning element and the efficiency of the filtration process is a function of the spinner's rotational speed. In prior systems of this general type as sold by the

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4 WO 89/07002 PCT/US89/00412 -6assignee), spinner rpm was maintained at a substantially fixed value 3600 rpm). Now, however, the rpm is preferably controlled to be a function linear) of input blood flow over some predetermined range). At lower input blood flow rates, it may also be desirable to controllably limit the plasma filtrate flow to a maximum value which may also be a linear function of input blood flow rate).

4. Brief description of the Drawings These as well as other objects and advantages of this invention will be better understood and appreciated by carefully studying the following detailed description of a presently preferred exemplary embodiment of this invention when taken in conjunction with the accompanying drawings, of which: FIGURE 1 is a schematic diagram of a portion of an exemplary plasmapheresis system of the type described in related U.S.

application No. 671,576) adapted to controllably reduce filter efficiency as a function of input blood flow rate; FIGURE 2 is a graph showing the manner in WO 89/07002 PCT/US89/00412 -7which spinner rpm (and hence filter efficiency) is controlled as a function of input blood flow rate; and FIGURE 3 is a flow diagram if a computer program segment which might be used in the FIGURE 1 embodiment for effecting the control depicted in the graph of FIGURE 2.

Detailed Description of an Exemplary Embodiment The blood plasmaphezesis system schematically depicted in FIGURE 1 represents a modification of the system described in more detail in related publication and earlier incorporated herein by reference. Similar reference numbers have been used in FIGURE 1 so as to facilitate a more detailed understanding of the system by reference to the related publication.

In brief, blood extracted from a donor and subsequently treated with an anti-coagulant is provided via conduit 70 and controlled blood pump 58 to the inlet 50 of a spinning filter system 12 (which includes a spinning filter membrane 40 rotated by motor 44). A plasma filtrate is extracted after passage through the spinning filter membrane via conduit 54 to plasma filtrate collection bag 22 while a cell concentrate residue from the filter system 12 WO 89/07002 PCT/US89/00412 -8is returned via outlet 52, controlled pump 60 and conduit 82 to a concentrate container Periodically upon substantial filling of container 20), the cell concentrate is typically reinfused to the donor. Preferably a single needle system is used where both blood extraction and reinfusion processes time share the same needle as in the Autopheresis-C device sold by Baxter Healthcare Corporation of Deerfield, Illinois). As will be understood, a plural, needle system may also be used with this invention. And, alternatively, the concentrate may be retained and used for other purposes as will be appreciated.

Pressure sensor 16 is coupled to the inlet of the filter system 12 and is capable of providing an output which represents transmembrane pressure (TMP) via control line 86 to a microprocessor control subsystem 18, Pumps 58 and 60 are typically conventional peristaltic pumps which are controlled by digital speed control signals and which also provide digital position indicating feedback signals via control lines 64, 66 and 74, 76 respectively, Electrical motor 44 is similarly capable of control (and position indicating output) with microprocessor control subsystem 18 via control lines 44a.

As indicated in FIGURE 1, the microprocessor control subsystem 18 may include optimized TMP operating point control as explained in WO 89/07002 PCT/US89/00412 -9more detail in the related publication noted above.

In addition, it now includes controlled reduction of spinner rpm so as to controllably reduce the efficiency of the spinning filter system 12 as a function of input blood flow. It will be noted, for example, that the plasma flow (PF) is equal to the input blood flow (BF) less the cell concentrate flow

(CF).

For example, as depicted graphically in FIGURE 2, the rotational speed rpm) of motor 44 is now controlled as a linear function of the input blood feed rate BF in milliliters per minute) ii accordance with the following formula: rpm 2,000 1600 (BF/100) (Equation 11 As will be appreciated, the maximum speed of motor 44 continues to be 3600 rpm as shown by a dashed line in FIGURE 2 but may be empirically optimized for various membrane and separation device configurations. In the exemplary embodiment, it is assumed that the blood flow does not exceed 100 milliliters per minute (or that, if it does, the spinner speed could be increased beyond 3600 rpm at higher input flow rates). It should be understood that the maximum spinner rpm and maximum input flow rate parameters are based upon the preferred embodiment but that these values may change with other design changes changes in membrane WO 89/07002 PCT/US89/00412 material, radius of the membrane rotor, area of the membrane or gap size, etc). In commercial systems of this type, when the input blood flow falls below a predetermined threshold 60 milliliters per minute), sustained plasma separation is impractical and in the Autopheresis-C device sold by Baxter Healthcare Corporation, sustained plasma separation is intentionally stopped below this lower limit, or predetermined value. "Predetermined value" is the value below which the machine instructs sustained plasma separation to cease. The reduced spinner rpm and resultant reduced filter efficiency of the exemplary embodiment occur at an input flow rate range immediately above the predetermined value, Such reduced efficiency creates a predetermined value for the lower limit of input blood flow rate that will enable satisfactory plasma separation) which is loWQr than the predetermined value which was heretofore feasible, This may be especially important for therapeutic procedures where a patient/donor blood circulation system i- in poor condition making higher level blood flows undesirable or even impossible, Measurements indicate that if the rotor speed of the filter in FIGURE 1 is reduced from 3600 rpm to zero rpm, the available plasma flow is reduced by a factor of about 50. Accordingly, at low blood flow input rates there are rotor sp.eds that can be used to reduce the efficiency as desired. Although a WO 89/07002 PCT/US89/00412 -1llinear relationship hns been established between input blood flow rate and splnner rpm in the exemplary embodiment, it will be appreciated that other functional relat~onships can be used as well, Furthermore, although the exemplary embodiment utilizes a particular presently preferred slope for this linear relationship, other linear control curve/slopes could also be implemented, in the exemplary embodiment, other conventional filter control systems cortnuQ to be employed as in the past TMP operating point optimization, donor vein pressure control subsystems, etc). However, in addition to such conventional controls, a very simple further control can be effected as already described by simply implementing a further computer program subroutine such as that depicted in FIGURE 3 each time a filter control cycle is performed by the microprocessor 18), Here, upon entry at 300, the new spinner rpm is calculated at 302 in accordance with the functional relationship of FIGURE 2 using the current m6asured or commanded value for blood flow input rate BF, If a further control below a predetermined threshold is desired, then a test for the threshold may be made and, if appropriate, a status flaq may be set and the filtrate flow rate BF is set to be no 4! more than a maximum value which also could be a linear function of blood flow input, as well) iQ 89/07002 PCT/US89/00412 -12before the thus derived commands are output to motor contr.ls at 308 and the usual return from the subroutine is taken at 310.

If overshoots or oscillations of TMP are encountered, then it may also be desirable to control the maximum slew rate for increasing plasma flow to be no more than about 1 to 3 milliliters per minute per second.

Although only one exemplary embodiment has been described in detail, those skilled in the art will recognize that many variations and modifications may be made in this exemplary embodiment while still retaining many of the novel features and advantages of this invention, Accordingly, all such variations and modificationa are intended to be included within the scope of the appended claims.

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Claims (25)

1. A fluid filtering system comprising: a fluid filter having controllable efficiency in separating a filtrate from an input fluid flow and providing a concentrate output fluid flow; and control means connected to controllably decrease fi"ter efficiency sufficiently to prevent excessive concentration of the concentrate output.

2. A fluid filtering system as in claim 1 wherein: said fluid filter includes a rotatable spinner element; and said control means controls rotational speed of the spinner element as a function of input fluid flow.

3. A fluid filtering system as in claim 2 wherein said control means controls rotational speed of the spinner element as a linear function of input fluid flow rate over at least a range of irput fluid flow rates.

4. A fluid filtering system as in claim 1, 2, or 3 further comprising means for eliminating 4 11 -j WO 89/07G02 PCT/US89/00412 -14- sustained flow of said filtrate when input fluid flow rate is below a predetermined value.

A fluid filtering system as in claim 4 wherein said predetermined value is substantially less than that attainable without reduced filter efficiency.

6. A fluid filtering system as in claim wherein said predetermined value is substantially less than 60 milliliters per minute.

7. A fluid filtering system as in claim 3 where in said control means controls the revolutions-per-minute of the spinner element to approximate 2000 plus 16 times the input fluid flow rate in milliliters per minute.

8. A fluid filtering system as in claim 1, 2, 3 or 7 adapted for plasmapheresis of blood by inclusion of a filter membrane on a spinner suitable for substantially passing blood plasma therethrough while substantially not passing blood cells and wherein the input fluid flow includes blood, the filtrate includes plasma separated from said blood and the concentrate output includes concentrated blood cells having a hematocrit substantially higher than that of the input blood flow and wherein said filter efficiency is controlled as a function of input fluid flow. S j( L-

9. A fluid filtering system as in claim 8 wherein said control means includes TMP control means for maintaining transmembrane pressure across said filter membrane at an optimized operating point where substantially only reversible blood cell blocking of the membrane occurs.

A blood plasmapheresis system comprising a spinning producing blood cell concentrate and to control operating transmembrane pressure to approximately maximize filtrate plasma flow without irreversible filter clogging, and, speed control means for controllably changing the rotational speed of said spinning filter element as a :plasmapheresis system to prevent excessive hematocrit of said blood cell concentrate.

11. A blood plasmapheresis system as in claim 10 wherein said speed control means controls filter element rpm as a function of blood flow rate input to the filter.

12. A blood plasmapheresis rystem as in claim 11 wherein said rpm is controlled as a linear function of input blood flow rate over at least a predetermined range of input flow rates.

13. A blood plasmapheresis system comprising a spinning filter element to separate plasma from blood thereby producing blood cell concentrate and to control operating transmembrane pressure to approximately maximize filtrate plasma flow without irreversible filter clogging, and, p* i c -1.6- filter efficiency control means for controllably reducing the efficiency of said spinning filter element as a function of a predetermined operating parameter of the plasmapheresis system to prevent excessive hematocrit of said blood rall concentrate.

14. A blood plasmapheresis system as in claim 13 wherein said control means controls filter element rpm as a function of blood flow rate input to the filter.

15. A blood plasmapheresis system as in claim 14 wherein said rpm is controlled as a linear function of input blood flow rate over at least a predetermined range of input flow rates.

16. A fluid filtering method comprising:- passing input fluid through a fluid filter having controllable efficiency, separating a filtrate flow from said input fluid flow via said filter and providing a concentrate :output fluid flow; and n ee^ WO 89/07002 PCT/US89/00412 -17- controllably decreasing efficiency of said filter sufficiently to prevent excessive concentration of the concentrate output.

17. A fluid filtering method as in claim 16 wherein said controllably decreasing step is performed in response to variations in the input fluid flow rate.

18. A fluid filtering method as in claim 16 wherein: said separating step is performed using a rotatable spinner element; and said controllably decreasing step includes control of the rotational speed of the spinner element as a function of input fluid flow.

19. A fluid filtering method as in claim 18 wherein said controllably decreasing step includes control of rotational speed of the spinner element as a linear function of input fluid flow rate over at least a range of input fluid flow rates.

20. A fluid filtering method as in claim 16, 19, or 20 further comprising eliminating sustained flow of said filtrate when input fluid flow rate is below a predetermined value. WO 89/07002 PCT/US89/00412 -18-

21. A fluid filtering method as in claim wherein said predetermined value is substantially less than that attainable without reduced filter efficiency.

22. A fluid filtering method as in claim 21 wherein said predetermined value is substantially less than 60 milliliters per minute,

23. A fluid filtering method as in claim 19 where in said controllably decreasing step includes control of the revolutions-per-minute of the spinner element to approximate 2000 plus 16 times the input fluid flow rate in milliliters per minute.

24. A,fluid filtering method as in claim 16, 18, 19 or 22, including plasmapheresis of blood by use of a filter membrane on a spinner suitable for substantially passing blood plasma therethrough while substantially not passing blood cells and wherein the input fluid flow includes blood, the filtrate includes plasma separated from said blood and the concentrate output includes concentrated blood cells having a hematocrit substantially higher than that of the input blood flow and wherein said filter efficiency is controlled as a function of input fluid flow.

25. A fluid filtering method as in claiim 24 including TMP control maintaining transmembrane I I C WO 89/07002 PCT/US89/00412 pressure across said filter membrane at an optimized operating point where substantially only reversible blood cell blocking of the membrane occurs. I) i