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A New Membrane Oxygenator-Dialyzer
A New Membrane Oxygenator-Dialyzer ARNOLD J. LANDE, M.D.; SERGE J. DOS, M.D. ROBERT G. CARLSON, M.D., F.AC.S. RICHARD A PERSCHAU; RICHARD P. LANGE LOUIS J. SONSTEGARD C. WALTON LILLEHEI, M.D., Ph.D., F.AC.S.
New membrane mounting devices designed to serve as efficient, mass-producible, and thus totally disposable blood pump-oxygenators or artificial kidneys have been designed and are currently undergoing development and testing. 10 This communication will describe these devices and report on preliminary tests of their function. Typical devices shown in Figure 1 mount 0.5 M2 (50 parallel blood flow paths) and 0.07 M2 (parallel blood flow paths) and measure ~/2 by 4 by 1 inch and 31f2 by 4 by 6 inches respectively. The smaller unit is intended to be a 24-hours per day, 7-days per week wearable artificial kidney. Membranes form the\basis for all hemodialyzers in use today. Such artificial kidneys function by diffusion across membranes from fluids which have excess concentrations of toxic substances (uremic blood) to fluids which do not (dialysis fluid). Ultrafiltration of water and small molecules may also occur when there is a significant pressure difference across the membranes. The great potential usefulness of membranes for blood oxygenation and CO 2 removal is perhaps less well known, especially in comparison with the familiar bubbling and filming types of blood oxygenators. In From the Departments of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, and Cornell Medical College-New York Hospital, New York, N.Y. Supported by Research Grants from U. S. Public Health Service (Grant HE-00830); Life Insurance Medical Research Fund; Minnesota Heart Association; Sussex County Heart Association, Newton, New Jersey; Maria and Joseph Gales Ramsay, III, Cardiovascular Research Fund; Max Baer Cardiovascular Research Fund; Fraternal Order of Eagles.
Surgical Clinics of North America- Vol. 47, No.6, December, 1967
1461
1462
ARNOLD
J.
LANDE, ET AL.
Figure 1. Membrane oxygenator, artificial kidneys, and principal components.
membrane oxygenators, dissolved gases diffuse across membranes from fluids having high partial pressures of respiratory gases to fluids having low partial pressures. Thus, oxygen diffuses into blood while CO 2 diffuses out, as in the human lung. Authors of many articles and textbooks suggest that membrane oxygenators cause less damage to blood than bubbling and filming types and would therefore seem more suitable for prolonged use in patients. 5 The crucial difference appears to be the absence of direct contact between blood and gaseous gas in membrane oxygenators, resulting in fewer physical and chemical stresses on blood in membrane oxygenators.ll Other potential advantages of rigidly supported membrane oxygenators are small and constant priming volumes. New membranes with excellent transport characteristics are becoming available for dialysis; however, the greatest recent advances have been in membranes for blood oxygenation. The best of these materials appears to be silicone rubber which is approximately 600 times more permeable to CO 2 than the membrane materials used previously and 60 times more permeable to oxygen. 6 The relatively low partial pressure difference driving COt out of blood (compared to the full atmosphere available to drive O 2 into the blood in artificial oxygenators) was previously the limiting factor. However, the respiratory gases are capable of passing through silicone rubber membranes in essentially physiologic proportions at physiologic partial pressure differences. Less than 1 M2 of 1 mil thick silicone rubber could theoretically provide basic support for an adult human.14 Thin strong membranes of silicone rubber are providing a great impetus toward development of membrane blood oxygenators. With the use of oxygenators which are relatively atraumatic to blood, one could undertake prolonged partial or total support for diseased cardiorespiratory systems without having to obtain oxygenated blood from the left atrium as in left heart bypass systems. Mere cannulation of peripheral veins and arteries would suffice for a support system that
A
1463
NEW MEMBRANE OXYGENATOR-DIALYZER
included a blood oxygenator, making use in the coronary care unit practica!,B Theoretical Considerations Influencing Design Exchange across membranes in dialyzers and oxygenators is limited by the number and size of pores or degree of solubility of the substance in the membrane, by the rate of diffusion through the membranes, and by the solubility and diffusion rates through the adjacent fluids themselves. The latter limitation might be minimized by utilizing vigorous turbulence to constantly place untreated blood next to the membrane to maintain high concentration or partial pressure gradients; however, this would be harmful to blood. Therefore, other ways of reducing the "boundary layers" of laminar flowing blood must be sought. On the gas or dialysate side turbulence may, of course, be used without ill effect. Ultra-thin films of blood are most helpful in reducing boundary layers since they reduce the distance that solutes must diffuse through blood. Ideally, every red cell would be within range of diffusion of O 2 and CO 2 during the time that it is between membranes. However, it would be difficult if not impossible to produce flowing blood films in the range of 8 microns thick as in true capillaries, without duplicating the large membrane surfaces of true lungs. 15 The artificial lung designer can take advantage of 100 per cent oxygen and the high solubility and diffusibility of CO 2 through silicone rubber in order to arrive at a practical solution. Poiseuille's law (Fig. 2) relates the variables one has to consider in designing a laminar flow blood oxygenator or artificial kidney. It is necessary to keep the pressure drop (resistance) through the device within practical limits while the height (thickness) of the blood film is kept as low as possible so that efficient exchange may occur. Blood flow rate through the device must be sufficient to satisfy the needs of the patient. Since viscosity may be influenced but little, one is left with length and width of the flow path as the principal variables which may be readily altered to provide efficient function. Short, wide flow paths are needed and their practical equivalents are multiple, short, parallel flow paths.3 An interesting concept which could increase the efficiency of these devices is that of Crescenzi and Claff,4 who gained increased efficiency of oxygenation by intermittently increasing the pressure of oxygen surrounding membranes in order to form extremely thin blood films repeatedly between membranes, low resistance flow being allowed between times.
PRESSURE DROP
-
Length
][
viscosity ][ flow rate
Height3
]l
Width
Figure 2. Poiseuille's Law for Wide Ducts. Length and width must be balanced for maximum performance and practicality.
1464
ARNOLD
J.
LANDE, ET AL.
Practical Design Problems and Solutions Manifolding (distributing) of both blood and oxygen or dialysate in and out of their respective multiple functional flow paths must be accomplished and provisions for countercurrent flow provided if possible. Precise rigid support for membranes should be provided to minimize short circuits which would be caused by low resistance preferential flow paths through the device. Potential leaks between blood and oxygen or dialysate must also be rendered unlikely. Figures 3 and 4 illustrate a method for accomplishing these objectives. This type of design was first utilized by Esmond in his early heat exchanger7 and is currently being used by Bluemle2 and Leonard13 for their dialyzer designs. The membrane is pleated as shown, leaving thin flow paths on
Figure 3. Blood must be kept separate from gas or dialysate.
Figure 4. Pleats form thin fluid spaces on opposite sides of a membrane.
A
NEW MEMBRANE OXYGENATOR-DIALYZER
1465
Figure 5. Pleats and plastic plates provide basic structure and rigidly define fluid flow paths.
opposite sides. It should be specifically noted that the multiple parallel flow paths for blood are on one side of a continuous membrane while gas or dialysate are relegated to flow paths on the opposite side of the same continuous membrane. As long as there is no defect in the membrane, no mixing between the blood and gas or dialysate can occur. In the devices described herein, rigid support plates are inserted
:Figure 6. Injection molded "cone plates" (left) and dye cut "frame plates" (right).
1466
ARNOLD
J.
LANDE, ET AL.
Figure 7. Blood and gas or dialysate are manifolded into multiple parallel counter-current flow paths 5 cm. in length.
Ql"
between the pleats from opposite sides of the membrane (Figure 5) in order to support the membrane precisely and rigidly. Preferential flow paths may thus be kept at a minimum. Injection molds and cutting dies have been designed and built to produce two types of plastic support plates (Fig. 6) for this purpose. The resulting unique combination of pleats and plates provides all needed structure, support, and manifolding. Figure 7 illustrates the manifolding of the blood and gas or dialysate into multiple streams and their subsequent filming between membranes in the functional portions of the devices. Blood and oxygen or dialysate run along the side of the stack of pleats and plates in grooves molded in plastic side plates before entering into low resistance channels directed across the devices. Both blood and oxygen or dialysate pass through slots in the separators allowing additional sealing between the fluid spaces and the outside of the apparatus. Blood then flows up in thin films within pleats of membrane while dialysate flows down on the far sides of the same pleats in the countercurrent direction, which is desirable for efficient use of dialysis fluid. Details of the molded cone plates are shown in Figure 8. These contain
A
NEW MEMBRANE OXYGENATOR-DIALYZER
1467
14,000 Bluemle cone supports} (7000 per side) which support the membrane intimately and firmly. Holes to mold these cones were drilled with a tape-controlled drill press to a depth of 0.024 inch and have a radius at their tips of 0.005 inch. They are arranged to miss the cones projecting toward them from the opposite cone plates in the assembled device. There is therefore no tendency for the delicate membrane to be squeezed or pinched between opposing cones. Flat-topped pedestals may be seen among the cones. These meet head-on in order to hold the cone plates at a precise distance from one another. The greatest distance between cones on a plate (diagonal) is exactly 0.040 inch, emphasizing the firmness of this membrane support system. Because of the pressure drop through the device, there would ordinarily be a tendency for the end of the fluid flow path where fluid enters to be distended in comparison to where fluids exits. To avoid this, provisions have been made to have higher cones on the blood entry side, which mechanically compress the otherwise distended blood film. In general, more metal has been left on this mold than is ultimately expected to be required. Thus, by repeated grinding and molding, a whole spectrum of support plates may be made available to be studied to determine the ideal configuration for any given purpose. Injection molding has been tried at various temperatures and pressures and with various materials. Polypropylene has been found ideal from most points of view, including steam sterilization. A simple cutting dye was built with which frame support plates may be made inexpensively from sheet plastics. Polypropylene has been found excellent for frame plates also. It should be noted that, although the molded cone plates are never in contact with blood, membrane always being interposed, the die-cut frame plates
Figure 8.
Membrane supporting "cones" and flat topped "pedestals."
1468
ARNOLD
J.
LANDE, ET AL.
do contact blood over a short distance and the relative inertness of polypropylene and its capacity to be treated by antithrombogenic methods 12 make it ideal. Assembly of these devices is simple and consists of laying down alternating types of plates while pleating a continuous strip of membrane over the structure so formed. This is a process which could be done by machine with minimal or no help from an unskilled worker. Side plates and end plates may be molded of plastic and complete units may be held together without leaks by conventional metal straps as used in packaging and crating. Thus, preas sembled, pretested, presterilized, and totally disposable units may come from the factory ready for immediate use. Results Testing in the laboratory has included both in-vitro and in-vivo experiments. Flow through single layer devices was observed visually by injecting a bolus of colored dye into a steady flow of water running through. Square front distribution and rapid washout of the dye were observed. It should be noted that in the study of dialysance illustrated in Figure 9, a 1: 1 ratio of blood to dialysis fluid flow was utilized to demonstrate the feasibility of wearable artificial kidneys for which available dialysis fluid would necessarily be limited. It has been shown that even greater efficiency may be obtained at higher dialysis fluid flow rates. Rate of oxygenation and CO2 removal are shown in Figure 10. In this study blood was treated which had had gases bubbled through it in order to adjust it to simulate severe respiratory acidosis. Full oxygenation occurred at a rate of 1000 cc. per minute per 1 M2 unit and almost complete oxygenation occurred at twice that rate of flow. Although CO 2 levels were not brought down to normal levels, a large percentage of CO2 was removed in this extreme example. PreDialysance vs Flows Per 1.0 m2 Cuprophane PT -150 Membrane (Extrapolated fram.O 5 m2 )
200 c
'E
"-
160
u u
(J)
u
c
120
Figure 9. Preliminary dialysance data utilizing low dialysate flow.
0
of>
>-
a
<5
80 40
o
400
800
Countercurrent Flaws cc/min Aqueous Solution "Blood" I Water "Dialysate" ~ I"
1200
A
1469
NEW MEMBRANE OXYGENATOR-DIALYZER
In-Vitro Arterialization (1/100 m2 of I mil Silicone Rubber Membrane - Extrapolated to I m2 ) pH
pC0 2
p0 2
%0 2
Venous Dog Blood Hgb 15 Adjusted to Simulate Severe Respiratory Acidosis ( 5 Samples mean)
7.10
85
49
69
Arterialized at 1.0 L/m2 Flow (10 Samples mean)
7.15
71
105
95
Arterialized at 2.0 L/m2 Flow (10 Samples mean)
7.13
73
77
90
Figure 10. Preliminary oxygenation data in simulated severe respiratory acidosis.
liminary in-vivo experiments have been carried out with 1/2 M2 units applied to dogs in a variety of systems. Both partial and total support have been provided for periods of eight and one hours respectively with survival. Veno-arterial pumping may be accomplished with the device itself by alternately increasing and decreasing the oxygen pressure. With one-way check valves included in the blood inflow and outflow lines, blood is propelled in one direction. Pumping against pressures in excess of 400 mm. Hg has been accomplished in this manner. Elimination of a separate pump appears to reduce blood trauma as measured in terms of plasma hemoglobin and platelet counts.
Plans A precise in-vitro testing program aimed at determining the exact flow pattern through single and multiple layer devices is being undertaken in the laboratory in order to maximize the performance of these units. Grimsrud and Babb9 have established that there is a precise blood film thickness which is capable of producing a peak maximum of solute exchange for a dialyzing unit of any given length. This peak potential of performance becomes higher, the shorter the flow path through the device. Therefore it should be possible to achieve quite a high peak of performance with this relatively short (5 cm.) flow path device. The results of this in-vitro work will be used not only to perfect the present device, but to aid in designing a next generation device, perhaps with shorter flow paths still. In-vivo testing in the laboratory will be directed toward systems for patient use.
1470
ARNOLD
J.
LANDE, ET AL.
Conclusions Membrane mounting devices for use both as membrane blood pump-oxygenators for surgery and artificial kidneys have been described and preliminary performance data given. These devices have many potential uses including support of infants with impaired pulmonary function (hyaline membrane disease) or severe cyanotic heart disease, and adults with chronic and acute impaired lung and heart function. Home and wearable artificial kidneys which are under development are expected to provide economical means for assisting the large number of patients who could benefit from this therapy. ACKNOWLEDGMENTS
We wish to acknowledge the invaluable assistance rendered by the Scientific Apparatus Shop of the University of Minnesota, Mr. Charles Henderson of Mold Designs, American Machine Company, Minnesota Plastics Company, Modern Tool Company, and the General Electric Company.
REFERENCES 1. Bluemle, L., Jr., Dickson, J., Mitchell, J., and Podolnick, M.: Permeability and hydrodynamic studies of the MacNeill-Collins Dialyzer using conventional and modified membrane supports. Trans. Am. Soc. Artif. Int. Organs, 6:38, 1960. 2. Bluemle, L., Jr., Ushakoff, A., and Murphy, W.: A compact blood dialyzer without membrane supports-design and fabrication. Trans. Am. Soc. Artif. Int. Organs, 11:157160,1965. 3. Clowes, G., Jr., and Hopkins, A.: Further studies with plastic films and their use in oxygenating blood. Trans. Am. Soc. Artif. Int. Organs, 1 :6-12,1956. 4. Crescenzi, A., and Claff, C.: A pulsatile extracorporeal membrane system. Proc. San Diego Symposium for Biomedical Engineering, pp. 27-31, 1963. 5. Dobell, A., Mitri, M., Galva, R., Sarkozy, E., and Murphy, D.: Biologic evaluation of blood after prolonged recirculation through film and membrane oxygenators. Ann. Surg. 161:617-622,1965. 6. Esmond, W., and Dibelius, N.: Permselective ultra-thin disposable silicone rubber membrane blood oxygenator: Preliminary report. Trans. Am. Soc. Artif. Int. Organs, 11 :325-329, 1965. . 7. Esmond, W., Stram, J., Kurad, W., Chyba, J., Attar, S., and Cowley, R.: Design and application of a disposable stainless steel blood heat exchanger with the integrated disposable plastic disc oxygenation system. Trans. Am. Soc. Artif. Int. Organs, 6:360-367, 1960. 8. Goldman, A., Boszormenyi, E., Utsu, F., Enescu, V., Swan, H., and Corday, E.: Venoarterial pulsatile partial bypass for Circulatory assist. Dis. Chest, 50:633-640, 1966. 9. Grimsrud, L., and Babb, A.: Optimization of dialyzer design for the hemodialysis system. Trans. Am. Soc. Artif. Int. Organs, 10:101-106, 1964. 10. Lande, A.: Comments during discussions. Trans. Am. Soc. Artif. Int. Organs, 13:1967 (in print). n. Lee, W., Crumhaar, D., Fonkalsrud, E., Schjeide, 0., and Maloney, J.: Denaturation of plasma proteins as a cause of morbidity and death after intracardiac operations. Surgery 50:29-39,1961. 12. Leininger, R.: Personal communication. 13. Leonard, E., Koffsky, R., Casterline, J., and Cascone, R.: A new tidal-flow dialyzer: In vivo, in vitro and mathematical assessment. Trans. Am. Soc. Artif. Int. Organs, 13: 1967 (in print). 14. Peirce, E. C., II: A new concept in membrane support for artificial lungs. Trans. Am. Soc. Artif. Int. Organs, 12:334-339, 1966. 15. Peirce, E. C., II, and Peirce, G.: The membrane lung-the influence of membrane characteristics and lung design on gas exchange, J. Surg. Res., 3:67-76,1963. 425 East 68th Street New York, N.Y. 10021 (Dr. Lande)
New membrane mounting devices designed to serve as efficient, mass-producible, and thus totally disposable blood pump-oxygenators or artificial kidneys have been designed and are currently undergoing development and testing. 10 This communication will describe these devices and report on preliminary tests of their function. Typical devices shown in Figure 1 mount 0.5 M2 (50 parallel blood flow paths) and 0.07 M2 (parallel blood flow paths) and measure ~/2 by 4 by 1 inch and 31f2 by 4 by 6 inches respectively. The smaller unit is intended to be a 24-hours per day, 7-days per week wearable artificial kidney. Membranes form the\basis for all hemodialyzers in use today. Such artificial kidneys function by diffusion across membranes from fluids which have excess concentrations of toxic substances (uremic blood) to fluids which do not (dialysis fluid). Ultrafiltration of water and small molecules may also occur when there is a significant pressure difference across the membranes. The great potential usefulness of membranes for blood oxygenation and CO 2 removal is perhaps less well known, especially in comparison with the familiar bubbling and filming types of blood oxygenators. In From the Departments of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, and Cornell Medical College-New York Hospital, New York, N.Y. Supported by Research Grants from U. S. Public Health Service (Grant HE-00830); Life Insurance Medical Research Fund; Minnesota Heart Association; Sussex County Heart Association, Newton, New Jersey; Maria and Joseph Gales Ramsay, III, Cardiovascular Research Fund; Max Baer Cardiovascular Research Fund; Fraternal Order of Eagles.
Surgical Clinics of North America- Vol. 47, No.6, December, 1967
1461
1462
ARNOLD
J.
LANDE, ET AL.
Figure 1. Membrane oxygenator, artificial kidneys, and principal components.
membrane oxygenators, dissolved gases diffuse across membranes from fluids having high partial pressures of respiratory gases to fluids having low partial pressures. Thus, oxygen diffuses into blood while CO 2 diffuses out, as in the human lung. Authors of many articles and textbooks suggest that membrane oxygenators cause less damage to blood than bubbling and filming types and would therefore seem more suitable for prolonged use in patients. 5 The crucial difference appears to be the absence of direct contact between blood and gaseous gas in membrane oxygenators, resulting in fewer physical and chemical stresses on blood in membrane oxygenators.ll Other potential advantages of rigidly supported membrane oxygenators are small and constant priming volumes. New membranes with excellent transport characteristics are becoming available for dialysis; however, the greatest recent advances have been in membranes for blood oxygenation. The best of these materials appears to be silicone rubber which is approximately 600 times more permeable to CO 2 than the membrane materials used previously and 60 times more permeable to oxygen. 6 The relatively low partial pressure difference driving COt out of blood (compared to the full atmosphere available to drive O 2 into the blood in artificial oxygenators) was previously the limiting factor. However, the respiratory gases are capable of passing through silicone rubber membranes in essentially physiologic proportions at physiologic partial pressure differences. Less than 1 M2 of 1 mil thick silicone rubber could theoretically provide basic support for an adult human.14 Thin strong membranes of silicone rubber are providing a great impetus toward development of membrane blood oxygenators. With the use of oxygenators which are relatively atraumatic to blood, one could undertake prolonged partial or total support for diseased cardiorespiratory systems without having to obtain oxygenated blood from the left atrium as in left heart bypass systems. Mere cannulation of peripheral veins and arteries would suffice for a support system that
A
1463
NEW MEMBRANE OXYGENATOR-DIALYZER
included a blood oxygenator, making use in the coronary care unit practica!,B Theoretical Considerations Influencing Design Exchange across membranes in dialyzers and oxygenators is limited by the number and size of pores or degree of solubility of the substance in the membrane, by the rate of diffusion through the membranes, and by the solubility and diffusion rates through the adjacent fluids themselves. The latter limitation might be minimized by utilizing vigorous turbulence to constantly place untreated blood next to the membrane to maintain high concentration or partial pressure gradients; however, this would be harmful to blood. Therefore, other ways of reducing the "boundary layers" of laminar flowing blood must be sought. On the gas or dialysate side turbulence may, of course, be used without ill effect. Ultra-thin films of blood are most helpful in reducing boundary layers since they reduce the distance that solutes must diffuse through blood. Ideally, every red cell would be within range of diffusion of O 2 and CO 2 during the time that it is between membranes. However, it would be difficult if not impossible to produce flowing blood films in the range of 8 microns thick as in true capillaries, without duplicating the large membrane surfaces of true lungs. 15 The artificial lung designer can take advantage of 100 per cent oxygen and the high solubility and diffusibility of CO 2 through silicone rubber in order to arrive at a practical solution. Poiseuille's law (Fig. 2) relates the variables one has to consider in designing a laminar flow blood oxygenator or artificial kidney. It is necessary to keep the pressure drop (resistance) through the device within practical limits while the height (thickness) of the blood film is kept as low as possible so that efficient exchange may occur. Blood flow rate through the device must be sufficient to satisfy the needs of the patient. Since viscosity may be influenced but little, one is left with length and width of the flow path as the principal variables which may be readily altered to provide efficient function. Short, wide flow paths are needed and their practical equivalents are multiple, short, parallel flow paths.3 An interesting concept which could increase the efficiency of these devices is that of Crescenzi and Claff,4 who gained increased efficiency of oxygenation by intermittently increasing the pressure of oxygen surrounding membranes in order to form extremely thin blood films repeatedly between membranes, low resistance flow being allowed between times.
PRESSURE DROP
-
Length
][
viscosity ][ flow rate
Height3
]l
Width
Figure 2. Poiseuille's Law for Wide Ducts. Length and width must be balanced for maximum performance and practicality.
1464
ARNOLD
J.
LANDE, ET AL.
Practical Design Problems and Solutions Manifolding (distributing) of both blood and oxygen or dialysate in and out of their respective multiple functional flow paths must be accomplished and provisions for countercurrent flow provided if possible. Precise rigid support for membranes should be provided to minimize short circuits which would be caused by low resistance preferential flow paths through the device. Potential leaks between blood and oxygen or dialysate must also be rendered unlikely. Figures 3 and 4 illustrate a method for accomplishing these objectives. This type of design was first utilized by Esmond in his early heat exchanger7 and is currently being used by Bluemle2 and Leonard13 for their dialyzer designs. The membrane is pleated as shown, leaving thin flow paths on
Figure 3. Blood must be kept separate from gas or dialysate.
Figure 4. Pleats form thin fluid spaces on opposite sides of a membrane.
A
NEW MEMBRANE OXYGENATOR-DIALYZER
1465
Figure 5. Pleats and plastic plates provide basic structure and rigidly define fluid flow paths.
opposite sides. It should be specifically noted that the multiple parallel flow paths for blood are on one side of a continuous membrane while gas or dialysate are relegated to flow paths on the opposite side of the same continuous membrane. As long as there is no defect in the membrane, no mixing between the blood and gas or dialysate can occur. In the devices described herein, rigid support plates are inserted
:Figure 6. Injection molded "cone plates" (left) and dye cut "frame plates" (right).
1466
ARNOLD
J.
LANDE, ET AL.
Figure 7. Blood and gas or dialysate are manifolded into multiple parallel counter-current flow paths 5 cm. in length.
Ql"
between the pleats from opposite sides of the membrane (Figure 5) in order to support the membrane precisely and rigidly. Preferential flow paths may thus be kept at a minimum. Injection molds and cutting dies have been designed and built to produce two types of plastic support plates (Fig. 6) for this purpose. The resulting unique combination of pleats and plates provides all needed structure, support, and manifolding. Figure 7 illustrates the manifolding of the blood and gas or dialysate into multiple streams and their subsequent filming between membranes in the functional portions of the devices. Blood and oxygen or dialysate run along the side of the stack of pleats and plates in grooves molded in plastic side plates before entering into low resistance channels directed across the devices. Both blood and oxygen or dialysate pass through slots in the separators allowing additional sealing between the fluid spaces and the outside of the apparatus. Blood then flows up in thin films within pleats of membrane while dialysate flows down on the far sides of the same pleats in the countercurrent direction, which is desirable for efficient use of dialysis fluid. Details of the molded cone plates are shown in Figure 8. These contain
A
NEW MEMBRANE OXYGENATOR-DIALYZER
1467
14,000 Bluemle cone supports} (7000 per side) which support the membrane intimately and firmly. Holes to mold these cones were drilled with a tape-controlled drill press to a depth of 0.024 inch and have a radius at their tips of 0.005 inch. They are arranged to miss the cones projecting toward them from the opposite cone plates in the assembled device. There is therefore no tendency for the delicate membrane to be squeezed or pinched between opposing cones. Flat-topped pedestals may be seen among the cones. These meet head-on in order to hold the cone plates at a precise distance from one another. The greatest distance between cones on a plate (diagonal) is exactly 0.040 inch, emphasizing the firmness of this membrane support system. Because of the pressure drop through the device, there would ordinarily be a tendency for the end of the fluid flow path where fluid enters to be distended in comparison to where fluids exits. To avoid this, provisions have been made to have higher cones on the blood entry side, which mechanically compress the otherwise distended blood film. In general, more metal has been left on this mold than is ultimately expected to be required. Thus, by repeated grinding and molding, a whole spectrum of support plates may be made available to be studied to determine the ideal configuration for any given purpose. Injection molding has been tried at various temperatures and pressures and with various materials. Polypropylene has been found ideal from most points of view, including steam sterilization. A simple cutting dye was built with which frame support plates may be made inexpensively from sheet plastics. Polypropylene has been found excellent for frame plates also. It should be noted that, although the molded cone plates are never in contact with blood, membrane always being interposed, the die-cut frame plates
Figure 8.
Membrane supporting "cones" and flat topped "pedestals."
1468
ARNOLD
J.
LANDE, ET AL.
do contact blood over a short distance and the relative inertness of polypropylene and its capacity to be treated by antithrombogenic methods 12 make it ideal. Assembly of these devices is simple and consists of laying down alternating types of plates while pleating a continuous strip of membrane over the structure so formed. This is a process which could be done by machine with minimal or no help from an unskilled worker. Side plates and end plates may be molded of plastic and complete units may be held together without leaks by conventional metal straps as used in packaging and crating. Thus, preas sembled, pretested, presterilized, and totally disposable units may come from the factory ready for immediate use. Results Testing in the laboratory has included both in-vitro and in-vivo experiments. Flow through single layer devices was observed visually by injecting a bolus of colored dye into a steady flow of water running through. Square front distribution and rapid washout of the dye were observed. It should be noted that in the study of dialysance illustrated in Figure 9, a 1: 1 ratio of blood to dialysis fluid flow was utilized to demonstrate the feasibility of wearable artificial kidneys for which available dialysis fluid would necessarily be limited. It has been shown that even greater efficiency may be obtained at higher dialysis fluid flow rates. Rate of oxygenation and CO2 removal are shown in Figure 10. In this study blood was treated which had had gases bubbled through it in order to adjust it to simulate severe respiratory acidosis. Full oxygenation occurred at a rate of 1000 cc. per minute per 1 M2 unit and almost complete oxygenation occurred at twice that rate of flow. Although CO 2 levels were not brought down to normal levels, a large percentage of CO2 was removed in this extreme example. PreDialysance vs Flows Per 1.0 m2 Cuprophane PT -150 Membrane (Extrapolated fram.O 5 m2 )
200 c
'E
"-
160
u u
(J)
u
c
120
Figure 9. Preliminary dialysance data utilizing low dialysate flow.
0
of>
>-
a
<5
80 40
o
400
800
Countercurrent Flaws cc/min Aqueous Solution "Blood" I Water "Dialysate" ~ I"
1200
A
1469
NEW MEMBRANE OXYGENATOR-DIALYZER
In-Vitro Arterialization (1/100 m2 of I mil Silicone Rubber Membrane - Extrapolated to I m2 ) pH
pC0 2
p0 2
%0 2
Venous Dog Blood Hgb 15 Adjusted to Simulate Severe Respiratory Acidosis ( 5 Samples mean)
7.10
85
49
69
Arterialized at 1.0 L/m2 Flow (10 Samples mean)
7.15
71
105
95
Arterialized at 2.0 L/m2 Flow (10 Samples mean)
7.13
73
77
90
Figure 10. Preliminary oxygenation data in simulated severe respiratory acidosis.
liminary in-vivo experiments have been carried out with 1/2 M2 units applied to dogs in a variety of systems. Both partial and total support have been provided for periods of eight and one hours respectively with survival. Veno-arterial pumping may be accomplished with the device itself by alternately increasing and decreasing the oxygen pressure. With one-way check valves included in the blood inflow and outflow lines, blood is propelled in one direction. Pumping against pressures in excess of 400 mm. Hg has been accomplished in this manner. Elimination of a separate pump appears to reduce blood trauma as measured in terms of plasma hemoglobin and platelet counts.
Plans A precise in-vitro testing program aimed at determining the exact flow pattern through single and multiple layer devices is being undertaken in the laboratory in order to maximize the performance of these units. Grimsrud and Babb9 have established that there is a precise blood film thickness which is capable of producing a peak maximum of solute exchange for a dialyzing unit of any given length. This peak potential of performance becomes higher, the shorter the flow path through the device. Therefore it should be possible to achieve quite a high peak of performance with this relatively short (5 cm.) flow path device. The results of this in-vitro work will be used not only to perfect the present device, but to aid in designing a next generation device, perhaps with shorter flow paths still. In-vivo testing in the laboratory will be directed toward systems for patient use.
1470
ARNOLD
J.
LANDE, ET AL.
Conclusions Membrane mounting devices for use both as membrane blood pump-oxygenators for surgery and artificial kidneys have been described and preliminary performance data given. These devices have many potential uses including support of infants with impaired pulmonary function (hyaline membrane disease) or severe cyanotic heart disease, and adults with chronic and acute impaired lung and heart function. Home and wearable artificial kidneys which are under development are expected to provide economical means for assisting the large number of patients who could benefit from this therapy. ACKNOWLEDGMENTS
We wish to acknowledge the invaluable assistance rendered by the Scientific Apparatus Shop of the University of Minnesota, Mr. Charles Henderson of Mold Designs, American Machine Company, Minnesota Plastics Company, Modern Tool Company, and the General Electric Company.
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