WO1982003567A1 - Method and apparatus for treating blood and the like - Google Patents

Method and apparatus for treating blood and the like Download PDF

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Publication number
WO1982003567A1
WO1982003567A1 PCT/US1982/000449 US8200449W WO8203567A1 WO 1982003567 A1 WO1982003567 A1 WO 1982003567A1 US 8200449 W US8200449 W US 8200449W WO 8203567 A1 WO8203567 A1 WO 8203567A1
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Prior art keywords
blood
fraction
means
filtration
filtrate
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PCT/US1982/000449
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French (fr)
Inventor
Eng Inc Biomedical
William John Dorson Jr
Meyer Markovitz
Vincent Beato Pizziconi
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Eng Inc Biomedical
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    • 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. haemofiltration, diafiltration
    • A61M1/3472Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration with treatment of the filtrate
    • 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. haemofiltration, diafiltration
    • A61M1/342Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424Substitution fluid path
    • A61M1/3431Substitution fluid path upstream the filter
    • A61M1/3434Substitution fluid path upstream the filter with pre-dilution and post-dilution
    • 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. haemofiltration, diafiltration
    • A61M1/342Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424Substitution fluid path
    • A61M1/3437Substitution fluid path downstream the filter, e.g. post-dilution with filtrate
    • 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. haemofiltration, diafiltration
    • A61M1/342Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3455Substitution fluids
    • A61M1/3458Substitution fluids having electrolytes not present in the dialysate
    • 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. haemofiltration, diafiltration
    • A61M1/342Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3455Substitution fluids
    • A61M1/3468Substitution fluids using treated filtrate as substitution fluid
    • 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. haemofiltration, diafiltration
    • A61M1/3472Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration with treatment of the filtrate
    • A61M1/3486Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
    • 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
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3601Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
    • A61M1/3603Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/24Dialysis ; Membrane extraction
    • B01D61/243Dialysis
    • 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/75General characteristics of the apparatus with filters
    • A61M2205/7563General characteristics of the apparatus with filters with means preventing clogging of filters
    • 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
    • A61M2206/00Characteristics of a physical parameter; associated device therefor
    • A61M2206/10Flow characteristics
    • A61M2206/16Rotating swirling helical flow, e.g. by tangential inflows

Abstract

Procede de traitement de fluides du corps, tels que le sang ou ses composants, et appareil approprie a ce procede. fluid processing method of the body, such as blood or its components, and apparatus suitable to this method. Un mode preferentiel de realisation consiste en un appareil de rein artificiel approprie pour nettoyer le sang du corps sans avoir besoin de grandes quantites d'eau pure comme cela est necessaire avec les appareils de rein existant actuellement. A preferential embodiment consists of an artificial kidney device appropriates to clean blood from the body without the need for large quantities of pure water as is necessary with existing kidney devices currently.

Description

METHOD AND APPARATUS FOR TREATING BLOOD AND THE LIKE

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to an improved method fo filtering biological fluids including blood and, more specifically, to a method for filtering the blood of the kidney patient in order to remove accumulated waste components.

2. Description of the Prior Art

The best known methods for removing waste materials from blood comprise various forms of dialysis. One involves passing the blood on one side of a semipermeable membrane and passing a dialyzing fluid containing suitable electrolytes on the other side of the membrane (process of hemodialysis). A portion of the blood water and low to moderate molecular weight waste materials diffuse through the membrane into the dialyzing fluid which must be continuously supplied in order to avoid electrolyte and toxin build-up which would stop or reduce the transfer of such materials from the blood. While units based on this principle are widely available and fairly reliable, they have several disadvantages. The system as a whole is relatively complex and cannot be made readily portable. In addition, trained operator is required. Treatment typically involves a visit to the hospital or the like on the order of three times a week to remove the accumulated toxic waste build-up, adjust electrolytes in the body and remove any excess water. In

O PI WIPO

SUBSTITUT addition to the expense of the treatment there is a problem that such a routine allows a much greater build-up of toxic waste in the body than does the normal kidney function so that there is a severe trade-off between efficacy and expense, including inconvenience.

Because of the above disadvantages of the dialysis method, researchers for many years have sought that replacement which would be more portable, might lead to more frequent use, and reduce the need for bulky, complex equipment and trained operators. One method which resulted from these efforts is described in the Markovitz U.S. Patent 3,483,867. That paten teaches the filtration of blood through a filter membrane under pressure to remove a portion of the water and associated waste materials, thereby eliminating the need for dialysis fluid and its attendant complications. Among the several variations of this method, one process includes passing the filtrate with its associated waste materials through a system of cartridges and secondary filters to selectively remove the waste materials and adjust the electrolytes. This purified fluid is then continuously returned to the bloodstream eliminating the need for large quantities of pure make-up water. Only minor replenishment of electrolytes might be required so that the general approach is capable of producing a portable unit suitable for use outside the hospital or dialysis center. One of many purposes of a secondary filter might be to isolate the entire

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C> l -~- -.-~,mn- m filtrate system for protection against bacterial and/or pyrogeni contamination. Another could be to trap intermediate sized species which pass through the first blood filter (hemofilter but would be rejected (retained) by the secondary filter. Thi application is shown schematically on Figures 1 and 2 where the different rejection characteristics of two filters are converte into a process for removing the intermediate sized species.

Despite large amounts of work on the general concept, th hemofiltration technique described above has never become practical because known filtration techniqes do not permit the required waste removal rate in order to cleanse the fluid (e.g. blood) in a reasonable time with a low membrane area without clogging the filter membrane with the rejected blood material.

This undesirable accumulation both reduces the removal rat efficiency and modifies the response of the filter. In the artificial kidney application the changes with accumulation woul be both lowered filtration efficiency and increased rejection of dissolved compounds. V7hile hemofiltration is potentially superior to hemodialysiε, such changes can make it worse than hemodialysis.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improved method for efficient ultrafiltration of blood or the like whereby reasonable filtrate rates and stable filtration characteristics may be achieved with lowered membrane areas

Figure imgf000005_0001
and/or treatment times.

It is the further object of this invention to provide an improved method for efficient filtering of blood, plasma or other body fluids whereby practical filtrate rates are obtained and components of predetermined molecular weight or size are removed in the filtrate.

It is still another object of this invention to provide an improved artificial kidney machine which allows removal of water together with low and moderate molecular weight toxic components in order to clear waste materials from a kidney patient.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In accordance with one embodiment of this invention, efficient ultrafiltration is achieved by spiral geometry filter means with the blood flow parallel to the axis of the spiral an filtrate removal along the spiral in order to provide efficient blood filtration.

In accordance with another embodiment of this invention, the ultrafiltration method includes the use of a spiral filter and recirculation through the filter of a major fraction of the blood leaving the filter.

In accordance with yet another embodiment of this invention, there is disclosed a method for filtering blood wherein a portion of the filtrate is recirculated back through the filter in order to achieve optimal filtration characteristics.

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SUBSTITUTE SHEET m r-m. WIPO The foregoing and other objects, features and advantages o the invention will be apparent from the following, mo particular description of the preferred embodiments of t invention, as illustrated in the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWING

Figure 1 shows the rejection characteristics of exemplary filters for use in this application.

Figure 2 shows schematically a portion of a filter syste for removal, as an example, of middle molecular weight materi from a feed fluid.

Figure 3 depicts important components of human blo including waste materials as a function of their molecular weig or cell size.

Figure 4 shows the filtrate rate versus pressur characteristics of a filter suitable for removal of low an middle molecular weight materials from the blood.

Figure 5 shows the clearance or removal rate versus th molecular weight of dissolved species as a function of th quantity of rejected materials (e.g. very high molecular weight proteins and/or cells) present on the filter membrane surface.

Figure 6 is a schematic representation of an ultrafiltratio system suitable for blood and the like.

Figure 7 is a plan view of a filter configuration suitable for use with the present invention.

^ E I

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^. . ^ mmm..-m, ----,-. — gj j-——. 1 WIPO

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-6- Figure 8 illustrates the effect of recirculation through the convective feed path of the filter on its efficiency as a function of the blood composition and operating variables.

DETAILED DESCRIPTION

Referring to Figure 3, the approximate distribution of constituents which make up human blood is shown as a function of either molecular or cell size. The major fractions A and B, spanning low and moderate molecular weights, include the electrolytes and at least a major portion of the toxins removed by the normal kidney. A third and fourth major fractions, C and D, of the blood have larger molecular weights and include proteins and antibodies. Fractions A, B, C and D together constitute the plasma portion of blood. The D fraction comprise molecular weights which range from approximately 45,000 to in excess of one million. Primarily platelets, red cells and white cells (the formed elements) exist in blood above the D fraction range .

Because of the relatively large molecular weight spacing between the plasma proteins (Fraction D) and Fractions A and B, ultraf iltration has the potential to permit selective removal of undesired constituents without disturbing the rejected major fractions (Fraction D and the formed elements). For example, removal of the water/electrolyte/ toxin reactions (A and B) by filtration of blood through a membrane having a pore size

Cf OMPI ϊ-Z-zτ ° corresponding to roughly a molecular weight in the range of 1,00 to 10,000 MW creates a filtrate which contains primarily Fracti

A and B in solution. It is then possible to treat this solutio in subsequent steps (e.g. ion exchange, sorption, a second o third filter, etc.) to purify and adjust the filtrate solutio

This allows the return of the cleansed and adjusted filtrate t the patient. Sequential filtration and processing of filtrat simulates the action of the normal kidney. Similarly, the use of a filter membrane having a pore size of between 0.1 and 0 microns can separate the plasma from the cellular formed element

(platelets, red cells, white cells). This would allow either the processing of plasma proteins for a wide variety of purpose

(e.g. combating immune deficient diseases) or the further separation and/or treatment of the different formed elements. O broad example is the selective removal of a single unwante component of middle molecular weight shown schematically o

Figures 1 and 2. Because most present filters have distribution of pore sizes, rejection may not occur precisely at and above a given particle size or molecular weight, but rathe increases over a limited range of particle sizes or molecula weights. To the extent that this range can be made to coincide with low concentration regions of the blood constituent spectrum, separation of the major blood constituents is possible. An intermediate component may be removed by the method depicted i

Figure 2. The method is also applicable to a wide variety of

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Figure imgf000009_0001
I O PI IPO particle suspensions including lymph fluids, animal blood, sewag components, milk and/or dairy product suspensions such as whe and xnicrobial suspensions.

In the so-called batch filtration process, the feed fluid i passed essentially normal to the plane of the filter. For fluid such as water containing suspended sand, batch filtratio is feasible as a semi-continuous process because the water ca continue to flow through the sand which builds up on the upstrea side of the filter and filtration continues with only moderat increases in pressure. Batch filtration is not suitable fo continuous use with whole blood because the larger constituents effectively clog the filter and engender large pressure increase for a given filtrate rate. Filtration of blood can be made mor efficient and continuous"by the use of a convective filter wher the feed fluid flows approximately parallel to the filte membrane and thus tends to carry off those constituents of th fluid which decrease the filtrate rate. The required flow o filtrate perpendicular to the filter membrane can still caus problems of clogging. The general problem is discussed a greater length in the co-pending patent application of Dorso Pizziconi, and Markovitz entitled "Method and Apparatus for Hig Efficiency Filtration of Complex Fluids", filed on April 13, 1981, U.S. Serial Number 252,795.

The clogging referred to herein can be two types? surfa clogging and membrane pore clogging. Surfaceclogging is cause

OMPI • /j.. IPO -* by rejected materials which accumulate on the surface (feed flui side) of the filter membrane. The amount and density of thi type can be controlled by the methods, devices, and procedures described or referenced in this disclosure. The second type o clogging refers to constituents of the blood or other body fluid becoming immeshed within the membrane ultrastructure. This is, in general, less affected by convective events within the feed channel although there is still a possible mino contribution from events within the feed channel. The basic membrane filtration characteristics would be altered in the latter case wherein a different straight line buffered saline limit could be encountered (e.g. the straight line of Figure 4 would be rotated clockwise). The initial technical concepts on membrane pore clogging as well as other limit phenomena were presented in the paper "Quantitation of Membrane- Protein-Solute Interactions during UltrafiItration" in Transations of the American Society for Artificial Internal Organs, Vol. 24, pg. 155, 1978. A more generalized and complete description of multiple limit phenomena supplemental to this disclosure was published in July, 1980 as the chapter entitled "Ultrafiltration of Plasma and Blood" in the book Advances in Biomedical Engineering, Part II, edited by D.O. Cooney (Marcel Dekker, Inc., New York and Basel).

Figure 4 shows how surface clogging affects the efficiency of filtration through its influence on the filtrate rate versus

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SUBSTITUTE SHEET V& rj, HO transmembrane pressure relationship. In that figure, filtrate rate is linearly proportional to pressure for a "buffered saline" solution. However, when proteins similar to those found in blood are added to the feed fluid, linearity fails and the pressure deviates from the ideal limit very dramatically at and above a certain filtrate rate determined by the nature of the feed fluid, the filter membrane, and the flow conditions (as examples). Figure 4 also shows graphically the definition of efficiency used herein; efficiency is the ratio of the filtrate rate, Nβ, on the non-linear curve to the filtrate rate, NA, on the linear buffered saline curve at the same transmembrane pressure. Note that the efficiency decreases at the pressure i increased. Low efficiency conditions at high pressures can result in gel or precipitate formation on the membrane surface as denoted by the indicated forbidden operational area.

Heretofore, attempts to treat blood by ultrafiltation have been either unsuccessful or of limited success because of inefficient filters. There are two major problems. First, while efficiency may be enhanced by moving from say point D to point in Figure 4 by reducing the pressure and filtrate rate, the rate becomes unacceptably low and may only be increased by making the filter large. In known configurations of filters for blood applications, area enlargement increases the total amount of protein deposition and in multi-channel designs aggravates the degradation of filtrate rate with time due to concentrating

_ OlvϊPI BSTITUTE SHEET effects. As regions of the filter begin to become ineffectiv either the filtrate rate drops or the transmembrane pressure (TMP) increases. The second major problem is that when th filter is operated inefficiently, the composition of the filtrate is modified. This is illustrated by Figure 5 where i may be seen that as the conditions change from points A ( protein) to B, C, and D (increased pressure, protein deposit, an density) in Figure 4 the filtrate includes less and less of the middle molecular weight species (e.g. Fraction B of Figure 3) In the case of the kidney application, for example, the clearanc rate can drop so low (e.g. curve D) that conventional hemodialysis rates (shown for comparison purposes) are more efficacious than hemo iltration clearances.

Figure 6 shows schematically a preferred embodiment of this invention in the form of a kidney machine suitable for long term therapy. Input blood is extracted, as an example, from the patient's artery or internal fistula/shunt and passes to the input port 30 of the apparatus. The blood then passes to inpu port 3 of the convective ultrafilter 1. A pressure differentia TMP, across the filter membrane 9 causes water and wast components to separate from the blood circuit chamber 4 and pass through the membrane to the filtrate plenum 6. A portion of the filtrate withdrawn from the filter 1 may be discarded as indicated by W to withdraw excess water from the patient. The remainder of the filtrate is passed through a processor 11

εϋCOTΪTUTΞ SHEET (e.g. cartridges, secondary filters, etc.) which removes waste materials (end products of metabolism, toxins) and adjusts the electrolyte concentration. The output of the processor 11 consists of water, electrolytes and nutrients at a rate F which is a fraction f of the input blood flow rate FF. This purified stream is returned to the patient and/or to the filter 1 as described in more detail hereinafter. That portion of the input blood which is not withdrawn as filtrate passes through and out of the convective filter at output port 5 of the filter and is returned to the patient's vein by way of apparatus output port

50.

Filter 11 preferably comprises a series of filters/cartridges each especially adapted to remove or change one or more of the plasma components. Suitable filters/cartridges are known to those skilled in the art and will not be described in detail here. Small quantities of makeup electrolytes, (such as calcium and magnesium), nutrients (such as glucose and/or amino acids) or medications (such as sodium bicarbonate, vitamins, etc.) may be added to the filtrate stream F which preferably also passes through a final bacterial filter before being returned to the patient; these details are not specifically shown in Figure 6.

In order to achieve and maintain efficient ultrafiltration through filter 1, the convective filter 1 must be especially configured and operated using one or more forms of augmentation

SUBSTITUTE SHEET herein defined as:

(1) surface perturbations in narrow flow channels

(2) irregular but controlled channel geometries

(3) membrane charge characteristics (repellant)

(4) secondary flow induction by channel inserts (screens, ribbons, etc. )

(5) externally applied forces and/or motions (physica movement, ultrasound, electrical potential, pressure perturbations, pulse flow, etc.

(6) staging of devices

(7) independent manipulation of flow rates in the device

(8) preferred geometries in combination with augmenting methods

(9) independent control of biochemical and biophysica conditions during filtration.

Referring now to Figure 7, various views of portions of suitable filter are shown. The input blood FF passes through th length L of the filter between the membrane elements 90. Elements 200 schematically represent a blood screen which serves to separate the membrane elements 90 by an appropriate distance, to introduce some resistance to flow into the blood path (whereb uniform flow is obtained) and to induce secondary flows which help keep the membrane clean. The model shown contains the membrane cast on a backing 400 sufficiently porous to allow easy flow of the filtrate towards the permeate collecting tube (500).

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SUBSTITUTE SHEET For the kidney machine, the total area of the membrane 9 on

Figure 6 is desirably on the order of 0.7 m for average adult intermittent application. The height H of the blood flow path is desirably in the range 0.25 to 1 mm? too small a value introduces excessive resistance into the blood flow path while too large a value results in inefficient filtration conditions and an impractically large filter.

In order that the filter 1 achieve and maintain efficiency, it is imperative that any impediments in the convective path do not appreciably reduce the effective width of the channel (i.e. active membrane) below its nominal value W. For example, if the filter consists of multiple hollow fiber membranes in a parallel arrangement, each with a bore diameter H, rapid plugging of a substantial number of the fibers can occur due to feed fluid concentration and the effective area is unacceptably diminished. Referring to Figure 7A, if a local impediment occurs in the channel, the blood must be able to continue to flow both upstream and downstream of the impediment. A rough geometrical criterion for such a condition is that W should be at least large as L. This requirement is most easily met by spiral filters, which are also compact and relatively easy to fabricate. Referring now to Figures 7B and 7C, there is shown a cross- section of a spiral filter. The membrane 9 (Figure 6) comprises an envelope with the backing 400 from two opposing membranes elements 90 in contact 99 and glued together at the outer edges 66. The envelope and the blood screen 200 are both wound around central hollow mandrel 500 which serves as a conduit for th filtrate stream F. The porous backing 400 from envelope 9 open only onto holes 300 leading to the hollow portion of the mandrel

500? the filtrate stream passes from the filter unit 1 throug the axis of the mandrel 500. Similarly, the blood passes throug the filter perpendicular to the drawing. More details of the construction of a spiral filter may be found in the Westmoreland

U.S. Patent 3,367,504, which describes its use for th desalinization of sea water.

Several different combinations of spiral wound constructio have resulted in achieving the high efficiency necessary for this application. In looking at the cross section perpendicular t the flow area, models have contained a blood side spacer, then the cast membrane, and then a filtrate mesh spacer. By casting the membrane directly onto a porous, woven, incompressible substrate, the filtrate spacer was eliminated, so that existing construction would consist of the blood side spacer and the membrane shown in the drawings herein. The membrane envelope i made by gluing the edges of the porous substrate together with a water-resistant adhesive, such as the urethane glue made by the

Hexel Corporation. Other adhesives used in the module construction include medical grade silicone (e.g. Dow Corning

Corp.) and possibly polymethylmethacralate or other adhesive strategies common in the field. The substrate materials have

£U£3τιτuτε SHEET been Dacron tricot or sailcloth stiffened with a melamine resin, while other materials, such as the DuPont Reemay, have also been used with success. Two types of membranes have been developed for this purpose with, apparently, equivalent results. The first type is an asymmetric cellulose acetate somewhat similar to the reverse osmosis membranes developed for desalinization.

Unlike the reverse osmosis application, changes had to be developed in order to allow free passage of electrolytes while rejecting the major plasma proteins. The changes in the process were either in formulation and annealing conditions or just in the annealing conditions. Two such formulations have been the glycerin perchlorate cellulose acetate formulation with altere annealing and the cellulose acetate annealed for short periods of time at less than or equal to 80° Centigrade. The main end point is to eliminate passage of molecules greatly in excess o

5,000 molecular weight, thus preventing the passage of at least the large proteins starting at 45,000 molecular weight.

Acceptable rejection criteria is shown as line A on Figure 5.

The exact annealing conditions will change with different cellulose acetate formulations and still produce an acceptabl membrane. The second type of membrane that can be used in hemofiltration is a modification of the newer, thin film composite reverse osmosis technology. The thin film composite reverse osmosis technology. The thin film composite reverse osmosis membranes are, typically, a backing similar to the on

O PI WIPO described above (substrate), a polysulfone intermediate membran and a thin top film (200-500 Angstroms) on top of the polysulfo

One top film for reverse osmosis has been a polyamid formulation. The modifications for hemof iltration can be eithe one of two types. The first is to cast a sufficiently thick polysulphone film with pore sizes to yield the rejectio characteristics given on Figure 5. Note that these rejectio characteristics given as curve A on Figure 5 would represent a acceptable transmission of larger molecules for hemof iltration purposes with the intent for artificial kidney purposes to transmit molecules normally present in urine. A concomitan membrane criteria would be insignificant passage of molecules at and above 45,000 molecular weight. This is better understoo with references to Figure 3, which shows the spectrum o molecules and formed elements in blood. The second modificatio of the thin film composite reverse osmosis technology would allo a thinner casting of the polysulfone base with an even thinne top film than is used in reverse osmosis. Again, the criteria i easy passage of electrolytes and end products of metabolism wit insignificant passage of the larger plasma proteins. All of th modifications outlined above are easily accomplished by technical personnel well versed in membrane technology.

In order to achieve efficient hemof iltration, the blood sid spacer 200 must have certain characteristics. Many thick commercial screens will not work due to their ineffectiveness in

Figure imgf000019_0001
S JEET promoting removal of rejected material away from the membrane surface. Conversely, extremely thin screens can result in too much pressure drop, which detracts from the transme brane pressure differential. One spacer that has worked is the Vexar, made by DuPont (polyethelene), with 12 strands to the inch an measuring a total thickness of approximately 25 mils. (0.025 inches). The preferred orientation is to have the mesh lines at an approximate angle of 45° to the flow direction as shown in

Figure 7A.

A preferred casting material to enclose the spiral filter and direct the blood and filtrate streams is polycarbonate or an equivalent biocompatible material. The same material has been used for the filtrate collection tube onto which the rolled spiral assembly is wound. The wound assembly is sufficiently smaller than the inside diameter of the polycarbonate housing, to enable potting of the wound assembly into the polycarbonate shell using medical grade silicone adhesive. Dimensions applicable to hemofiltration are a membrane width of 10 inches with a wound assembly diameter of 2 and 2/3 inches. This yields an effective membrane area considered to be a minimum for adult human intermittent application of 0.7 meters squared. Other details of construction are similar to existing spiral wound technology in the reverse osmosis field, with the exceptions of having to use biocompatible materials and avoiding turbulence in the blood flow path.

Figure imgf000020_0001
A filter in accordance with the foregoing description will still not result in efficient hemof i ltrat ion unless it i operated as now described. It has been found essential for maintenance of efficiency to recirculate a large fraction of the blood exiting the filter at port 5 by reintroducing it a input port 3 at recirculation rate R times the input blood flo rate FF. R must be substantially larger than 2 with a nominal

FF of 200 to 250 cc/min.; values on the order of 3-8 are require to assure high efficiency with the filter membranes and device used hitherto and described hereinbefore. While there is a present no comprehensive and exact theoretical basis for th relation of the value of R to the filter parameters and bloo composition, most factors are known and at least two factors ar believed substantial. First, the use of large amounts o recirculation R enhances the compositional homogeneity of th blood along the length of its flow path through the channel 4. typical blood input flow rate range is 200-250 cc/minute with typical filtrate rate of 80 cc/minute. Without recirculation, then, the plasma portion of the blood would be depleted o approximately half of its water by the time it reached output port 5. For example, if R = 4, then the filter input flow rate is in the range 1000-1250 cc/minute so that withdrawal of 80-100 cc/minute of water results in a much lower percentage change in blood composition down the length L of the filter. Second, the increased rate of flow through the filter with recirculation

OMPI

SUBSTITUTE SHEET &Swτiθ apparently results in an increased scrubbing action on the filter membrane whereby its clogging proclivity is reduced. A the blood access limited flow rate is increased, the value of can be decreased and still achieve high efficiencies.

Figure 8 gives data illustrative of the effect of th recirculation ratio R on the efficiency of the filter

Efficiency is very low without recirculation (R = 0) and then rises dramatically. In general, the larger the ratio of th operating variable, FF x R/T.P., the higher the filte efficiency. This efficiency relationship is further dependent on HCT, PH, TMP, and fibrinogen levels for a given filter design, i.e. H, W, L and screen design. The limit value for the efficiency ranges above 80% and depends inter alia on th variables indicated as well as other factors listed on Figure 8.

Because maximal efficiency may occur at positional values different from those of the patient's blood, efficiency may b maximized by differentially returning the filtrate flow F to th filter input port 3 and the patient blood return port 50. Fo example, for a non-anemic patient (HCT relatively high), it is desirable to return all of the filtrate flow F to the input o the convective filter 1. The above specification of geometries and operating conditions are based .on adult human intermittent application. Specifications for continuous treatment of bod fluids or pediatric applications, as examples, would be different (e.g. smaller membrane surface areas).

-^I3REA

OMPI TUTE SHEET t l WlPθ In addition to the preferred embodiments described above, following is a review of typical applications of liste augmentation methods. Surface perturbations in narrow flo channels can be achieved in several ways. One is to have th membrane exposed to the feed channel containing surfac irregularities which may, as an example, be achieved by castin the membrane over an underlying matrix which would promote th formation of the perturbations in the final membrane produc

Another method is to have the membrane supported by an irregula plastic insert with the transmembrane pressure sufficient t deform the membrane over the perturbation typically moded into the plastic support. An example of irregular but controlle channel geometries would include tight coiling of the feed channel, having periodic or asymmetric surface waviness paralle to the flow, and folding of the flow channel again in a manne to induce flow diversion in the direction of flow. For fee fluids containing charged molecules or particles to be rejected the membrane can be constructed to contain fixed repellant charges. In addition to the efficiency induction by screen covered in detail, a tubular blood channel can benefit by using ribbon to produce spiral flow (secondary flows) in addition to axial flow through the tube. Examples of externally applie forces can include, but are not restricted to, the applicati of surface charge (in the absence of significant membrane charge electrically induced with the insertion of electrodes in eithe

-fJ EX^

OMPI

SUBSTITUTE SHEET \^~wSδ- the membrane or support structure. In this way, a polarization parallel to the filtrate flow aids in repelling the rejected materials away from the membrane surface. Electrodes have been formed by using metallized screens to support the membrane along with a metallized flow channel bounding surface opposite from the surface of the membrane. Another augmentation technique involves the use of ultrasound for improving filtration efficiency. Instead of the metallized requirement, the material must have, as an example, piezoelectric properties.

To achieve ultrasound frequencies, discrete crystals would be required compared to only low frequencies available with single continuous sound drivers (e.g., reeds or electromagnetically driven diaphragms) in the feed channel. Ultrasound may be implemented in several ways, including crystals directly exposed to the feed channel. This is the most electrically efficient way of transmitting ultrasound frequency. It is also the least efficient in promoting filtration efficiency while posing the possibility of "heat" damage to the blood. A less electrically efficient way of producing ultrasound is to have the transducer face placed parallel to the direction of the feed flow, either in or underneath the membrane structure. Although less electrically efficient, the augmentation of filtration by the membrane is most effective with this orientation. Ultrasound reacts with any and all acoustic interfaces, one such important interface being the membrane/fluid junction.

SUBSTITUTE SHEET Ultrasound techniques include the use of a single frequency, frequency spectra, and combination of frequencies dependen upon the application. Examples of physical movement include

"washing machine" agitation, continuous rotation with speci rotating seals or connectors, or linear vibration, all applied t the entire filtering module. Staging of devices includes the use of more than one device arranged in a parallel and/or sequential manner. This allows direct introduction of cleanse filtrate into the feed flow between each module. This dilute the feed flow, allowing more efficient filtration in each module but normally at the price of increased total surface area (mor modules) with concomitant improvement in total clearance o effective filtration. These trade-offs are inherent in th implementation of staging and quantitative calculations can b made by individuals versed in controlling filtration phenomena

Staging may also be of the macrostage variety, in which selected reintroduction of filtrate can be achieved by desig along an otherwise continuous flow channel. Staging is als meant to imply any method of intermittently "mixing up" the fee stream to eliminate any component polarization within the fee stream. Another variation of staging also found to be effectiv is the alternating of active and inactive filtering areas.

This concept somewhat accomplishes the sequential mixing allude to above. Without any other augmenting method, the remixi would be by diffusional processes in the case of rejecte

ITUTE SHEET molecules. With the simultaneous use of other augmenting methods, convective modes of transport could assist the diffusion. Independent manipulation of flow rates in the device include, generally, any additional pumping or flow action addition to the simple throughput required to achieve practic filtration. Details have been given on the use of recirculatio in one of the preferred hemof i Itrat ion designs, but the invention would also include mechanical oscillatory motions t cause vortex shedding and/or fluid replenishment from grooves perpendicular to the mainstream feed flow, as an example of preferred geometries in combination with other augmentation methods. The more direct example herein is in the use of spiral hemofilter modules with screens capable of inducing hig efficiency in combination with recirculation of the exiting fluid back to the inlet. Since the hematocrit affects th production of optimum efficiency, variation of the reintroductio of filtrate between the module inlet and exit is also a method o improving the filtering efficiency, considered to be one of the biophysical condition embodiments. In addition to the methods already covered, independent control of biochemical and biophysical conditions includes the pH in the feed channel

(more importantly at the membrane surface), control over the charge at the membrane surface, and the fractional filtrate (f) return ratio.

HEET While the invention has been particularly described and shown in reference to the preferred embodiments thereof, it will be understood by those skilled in the art that various change in form and detail and omissions may be made therein withou departing from the spirit and scope of the invention.

Claims

We Claim:
1. An apparatus for the f iltration of predetermine molecular weight components from blood comprising convective f iltration means for separation of said blood into a firs fraction having high molecular weight components than said firs f ract ion, sa id f i lt rat ion means including at leas t on augmentation means for maintaining ef f iciency during sai filtration.
2. An apparatus for the f iltration of predetermine molecular weight components from blood, comprising convectiv filtration means for separation of said blood into a f irs fraction having high molecular weight components with cell and a filtrate fraction having lower molecular weight component than said first fraction, said means comprising spiral geometr augmentation means for maintaining efficiency during the period of said filtration.
3. A hemof iltration artificial kidney apparatus for the removal of toxic blood components from a patient's circulator system, comprising, in combination: means for receiving a blood stream from said patient ? convective f iltrat ion means for separation of said bloo stream into a f irst fraction having high molecular weight components with cells and a f iltrate fraction having lowe molecular we ight components than said f irst fraction, sai filtration means including at least one augmentation means fo maintaining efficiency during said filtration? auxiliary filtration means for treating said filtrate fraction by removing said toxic blood components? and means for returning said first fraction and said treated filtrate fraction to the circulatroy system for said patient.
4. A hemofifltration artificial kidney apparatus for the removal of toxic blood components from a patient's circulatory system, comprising, in combination: means for receiving a blood stream from said patient? convective filtration means for separation of said blood stream into a first fraction having high molecular weight components with cells and a filtrate fraction having lower molecular weight components than said first fraction, said means comprising spiral geometry augmentation means for maintaining efficiency during the period of said filtration? auxiliary filtration means for treating said filtrate fraction by removing said toxic blood components? and means for returning said first fraction and said treated filtrate fration to the circulatory system of said patient.
5. In a hemofiltration artificial kidney apparatus, the
improvement comprising spiral convective filtration means having at least one augmentation means for efficient separation o blood into a first fraction having high molecular weight components with cells and a filtrate fraction.
OMPI
6. In a hemofiltration artificial kidney apparatus, the improvement comprising spiral convective filtration means for efficient separation of blood into a first fraction having high molcular weight components with cells and a filtrate fraction.
7. The apparatus of any of Claims 1-6, further comprising means for recirculatinga portion of said first blood fraction through said convective filtration means to improve filtration efficiency.
8. The apparatus of any of Claims 1-6, further comprising means for recirculating a portion of said filtrate fraction through said convective filtration means to improve filtration efficiency.
9. The apparatus of any of Claims 1-6, further comprising first recirculation means for recirculating a portion of said first blood fraction through said convective filter means, and second recirculation means for recirculating a portion of said filtrate fraction through said convective filtration means, both of said recirculated portions improving filtration efficiency.
10. The apparatus of any of Claims 2, 4 or 6 wherein said convective filtration means comprises charged membrane means for repelling selected constituents in said blood.
11. The apparatus of Claims 1 or 2, further includin second convective filtration means for separation of said filtrat fraction into a second blood fraction having intermediate molecular weight components and a third blood fraction having low molecular weight components.
12. The apparatus of Claim 3 or 4, where said auxiliary filtration means comprises second convective filtration means for separation of said filtrate fraction into a second blood fraction having intermediate weight components and a third blood fraction having low molecular weight components.
13. The apparauts of Claim 12, where said second blood fraction comprises either said toxic components or other consitituents for further processing or removal.
14. The apparatus of any of Claims 1-6 where said convective filtration means comprises membrane means having a pore size which allows transmission of molecules normally present in urine.
15. The apparatus of Claim 2 or Claim 4 where said spiral filter means comprise at least one other augmentation means for maintaining efficiency of said filter means during the period of
said filtration.
16. The apparatus of Claim 15, further including recircultaion means for recirculating at least one of said first fraction and said filtrate fraction through said filtration means for improving the efficiency of said filtration means.
17. A method for removing predetermind components from blood, comprising the steps of filtering said blood through a convective filter for separating said blood into a heavy fraction having high molecular weight components with cells and a filtrate fraction having lower molecular weight components than said heavy fraction, said filter having at least one augmentation means for maintaining the efficiency of said filtering during the period thereof.
18. A method of removing predetermined components from blood, comprising the step of filtering said blood through spiral convective filter means for separating said blood into a heavy fracation having high molecular weight components and a filtrate fraction having lower molecular weight components than said heavy fraction.
19. A method for removing toxic blood components from the circulatory system of a kidney patient, including the steps of: withdrawing blood from said patient? filtering said blood through convective filter means having at least one augmentation means to achieve high efficiency separation of said blood into a heavy fration having high molecular weight components with cells and a filtrate fraction having lower molecular weight components than said heavy fraction? treating said filtrate stream to remove said toxic bloo components? and returning said treated filtrate stream and said heavy fraction to the circulatory system of said patient.
20. A method for removing toxic blood components from the circulatory system of a kidney patint, including the steps of : withdrawing blood from said patient? filtering said blood through spiral convective filter means to achieve high efficiency separation of said blood into a heavy fraction having high molecular weight components with cells and filtrate fraction having lower molecular weight components than said heavy fraciton? treating said filtrate stream to remove said toxic blood components? and returning said treated filtrate stream and said heavy fraction to the circulatory system of said patient.
21. The method of any of Claims 17-20, further including recirculating a portion of said heavy fraction through said filtration means to improve filtration efficiency.
22. The method of any of Claims 17-21, furhter including recirculating a portion of said filtrate fraction through sai filtration means to improve filtration efficiency.
23. The method of any of Claims 17-22, said method further comprising the step of exposing said blood in said convective filter means to charged membrane means for repelling selected constituents in said blood.
24. The method of Claims 19 or 20 where said step of treating said filtrate stream comprises filtering said filtrate fraction through second convective fi lter means to provide an intermediate fraction having intermediate molecular weight components and light fraction having low molecular weight components .
25. The method of Cla im 19, where said treatment step comprises discarding said intermediate fraction.
26. A method for removing plasma from blood, comprising the s tep of f i l t ler ing sa i d blood through spi ral convect ive filter means for separating said blood into a plasma fraction an a cellular fraction.
PCT/US1982/000449 1981-04-13 1982-04-13 Method and apparatus for treating blood and the like WO1982003567A1 (en)

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1985003011A1 (en) * 1983-12-29 1985-07-18 Amf Incorporated Cross-flow filtration related applications
WO1985004112A1 (en) * 1984-03-21 1985-09-26 Mclaughlin, William, Francis Method and apparatus for filtration
US5738792A (en) * 1984-03-21 1998-04-14 Baxter International Inc. Method for separation of matter from suspension
EP0156652A2 (en) * 1984-04-02 1985-10-02 FMC Corporation Spiral designed reactor
EP0156652A3 (en) * 1984-04-02 1988-05-04 Amerace Corporation Spiral designed reactor
WO1986002858A1 (en) * 1984-11-15 1986-05-22 Hemascience Laboratories, Inc. Adaptive filter concentrate flow control system and method
WO1986005410A1 (en) * 1985-03-13 1986-09-25 Baxter Travenol Laboratories, Inc. Platelet collection system
US4869812A (en) * 1985-08-12 1989-09-26 Baxter International Inc. Disposable diagnostic plasma filter dispenser
US6863821B2 (en) 2002-02-02 2005-03-08 Baxter International Inc. Shear-enhanced systems and methods for removing waste materials and liquid from the blood
US7182867B2 (en) 2002-02-02 2007-02-27 Baxter International Inc. Shear-enhanced systems and methods for removing waste materials and liquid from the blood
US7494591B2 (en) 2002-02-02 2009-02-24 Baxter International Inc. Shear-enhanced systems and methods for removing waste materials and liquid from the blood
US8961789B2 (en) 2008-10-31 2015-02-24 Baxter International Inc. Systems and methods for performing hemodialysis
US9757504B2 (en) 2008-10-31 2017-09-12 Baxter International Inc. Systems and methods for performing hemodialysis

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