Blood Oxygenation by Liquid Membrane Permeation - Advances in

1 Blood Oxygenation by Liquid Membrane Permeation N O R M A N N . L I and W I L L I A M J. A S H E R

Downloaded by 203.64.11.45 on February 18, 2015 | http://pubs.acs.org Publication Date: June 1, 1973 | doi: 10.1021/ba-1973-0118.ch001

Esso Research and Engineering Co., Corporate and Government Research Laboratories, Linden, N . J. 07036

Blood oxygenation is one of the many potential applications of the separation technique using liquid membranes. In this particular application, the blood is oxygenated by contacting with oxygen bubbles pre-coated with the membranes. The oxygen in the bubbles diffuses through the membrane into the blood, whereas the carbon dioxide diffuses from the blood into the bubbles. The exploratory results show that stable fluorocarbon-type liquid membranes were formed around oxygen bubbles, and such membranes allowed opposite transfer of oxygen and carbon dioxide at substantial rates. Blood damage, which usually occurs in conventional artificial lung devices, should be greatly reduced as previous studies have indicated good and perhaps unique compatibility of the liquid fluorocarbon and blood interface. The potential advantages that this new and unique oxygenation technique can offer over the currently available techniques are discussed.

" D l o o d oxygenation is one of the many potential applications of the -^separation technique using liquid membranes developed at Esso Research ( I , 2, 3, 4). In the presently available artificial lung devices, blood comes i n contact directly with oxygen bubbles, with oxygen at mosphere, or with oxygen that has permeated through a solid polymeric membrane. These devices have served admirably for short times—e.g., in surgery. However, they have had limited success for prolonged oxy genation, as might be used to a i d patients with reversible respiratory insufficiency. The two primary problems for prolonged oxygenation are: (1) blood hemolysis—the rupture of red blood cells—and (2) denatura1 In Chemical Engineering in Medicine; Reneau, D.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.


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C H E M I C A L ENGINEERING I N M E D I C I N E

tion of proteins i n the blood. Red cell ruptures and changes i n the char acteristic properties of blood proteins can occur easily when blood directly contacts oxygen or a non-compatible solid membrane surface. In the blood oxygenation application of liquid membranes, the blood contacts fluorocarbon liquid membranes which encapsulate oxygen bub bles. The blood may be shunted from the body and passed through a contacting device before being sent back to the body. The contacting device can have many different types of structure. One type is a column i n which the blood and the encapsulated oxygen bubbles flow countercurrently. The blood is the continuous phase i n which the encapsulated bubbles are dispersed uniformly by the method they are introduced into the column and by the flow existing in the column. The liquid mem branes encompass the oxygen bubbles completely, thus preventing the formation of a direct blood-oxygen interface while allowing oxygen to diffuse into the blood and carbon dioxide to diffuse from the blood to the gas bubbles. The liquid membranes are composed of fluorocarbon-type compounds because some seem to have good and perhaps unique com patibility with blood and no detectable chemical toxicity (6, 7, 8, 9, 10, 11, 12). Only fluorocarbon-type compounds, indicated to be bicompatible, were added to the blood and oxygen to form the liquid mem branes of this system. Thus, the liquid membrane oxygenation method has the potential advantages of minimizing blood hemolysis and protein denaturation. The resistance to 0 and C 0 transport of the liquid membrane should be minimal. The liquid membranes are typically quite thin. In systems where they have been measured, they are usually 1 ft or less, which is substantially thinner than polymeric membranes used for tranport. The thinness of the membranes combined with the high solubility of fluorocarbons (13, 14) for 0 and C 0 would be expected to lead to minimal liquid membrane resistance to transport. The geometry for transport mimics that of the body. The gas encapsuled i n the liquid membrane is the counterpart to the gas i n the alveoli of the lungs in the body. The normal transfer mechanism of oxygen i n blood is different than in simple solutions (15,16). The quantity of oxygen carried in plasma at atmospheric pressure is very small, about 0.2 m l at STP/100 m l of plasma, expressed as a gas volume at standard conditions per solution volume. Whole blood, in contrast, can carry about 20 m l at STP/100 m l of blood. The larger load of oxygen is carried in chemical combinations with hemo globin as expressed below: 2

2

2

2

Hemoglobin + Oxygen

Oxyhemoglobin

(1)

Hb +

Hb0

(2)

0

2

2

In Chemical Engineering in Medicine; Reneau, D.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.

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L i AND ASHER

The hemoglobin becomes saturated at about 100 m m H g 0 pressure, and further oxygen has to be dissolved i n the plasma. Advantages of Liquid Membrane Oxygenation


3

Oxygenation by Liquid Membrane 2

partial

Over Other Methods

Presently available oxygenators can be divided into two categories. One is for blood to be i n direct contact with oxygen; the other is for blood to be i n contact with the oxygen that permeates through a solid polymeric membrane. Oxygenating blood i n both types of oxygenator usually results i n some degree of damage to blood proteins and red cells. There is no apparent improvement or remedy that can be made for the first method. For the second method, industrial and academic research has been carried out to modify or treat the polymeric surface, like chemically bond heparin to the membrane surface to make it more compatible with the blood. However, it has not yet been established that polymeric membrane oxy genators can operate over prolonged times with truly negligible blood damage. The liquid membrane technique has the potential advantages of presenting a blood interface minimizing hemolysis and protein denaturation and of using deformable liquid membranes. The general advantages of liquid surfactant membranes over solid polymeric membranes have been discussed previously ( I , 2). They are summarized below: (1) Greater surface area for permeation and separation because of high surface area of liquid membranes per unit volume (2) Elimination of pinholes i n imperfect solid membranes, which allow all components of a mixture to pass through, just as a broken liquid membrane would (3) N o membrane life problem since the liquid membranes are recovered after each separation and no deposit (for example thrombus) can accumulate with time to decrease performance (4) A faster rate of permeation and separation since liquid mem branes are much thinner than solid ones (5) N o need for a mechanical support, such as the frames that hold solid membranes i n the mixtures being separated (6) N o minute flow channels to become blocked i n time with solids (e.g., thrombus) Experimental Philosophy. The exploratory results presented i n this paper do not represent the best accuracy that could be obtained with the methods described, nor do the in vitro conditions used always most closely ap>roach those which would be found in vitro. Also, the apparatus used was ar from optimal for blood oxygenation. However, the representative data reported indicate strongly new phenomenon and application for

Î




4

Figure 1.

Liquid membrane (LM) blood oxygenator

liquid membranes and suggest several avenues for future investigations. F o r these reasons, the representative exploratory data are presented. Apparatus. The liquid membrane oxygenator consists basically of a glass column of 11.5 inches i n height and 1.25 inches i n diameter (Figure 1). The bottom of the column was filled with the liquid fluorocarbon solution to a height of about 3 inches. The rest of the column was filled with blood all the way to the top. The oxygen and the carbon dioxide probes manufactured by Beckman Instrument and Variflo, re spectively, were submerged in the blood phase. They were used i n connection with a physiological gas analysis meter, manufactured by Beckman Instrument, to measure the oxygen and carbon dioxide partial pressures i n the blood. A stainless steel tube went through the bottom stopper as the nozzle through which oxygen bubbles were formed i n the liquid fluorocarbon solution. T w o tubes of different size, 0.3 cm and 0.05 cm i n diameter, were used i n separate runs for forming oxygen bubbles of different size. A wet test meter was used to measure the rate of oxygen gas going into the oxygenator. Materials. Bovine blood was used i n the experiments within 24 hours after being obtained fresh from a nearby slaughter house. To each quart of blood, 5 cc of solution containing 5000 U S P herapin units were added to prevent clotting. The liquid fluorocarbons used were manu-



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Oxygenation by Liquid Membrane

5

factured by DuPont and 3 M . The oxygen gas used was chemically pure (manufactured by Matheson C o . ) . Procedure. The liquid fluorocarbon and blood were slowly intro duced into the column just before the start of the run. The oxygen gas that had passed through the wet test meter was sent into the oxygenator through the stainless steel nozzle at low rate, such as 40 cc/min. W h e n liquid membranes were to be made, the nozzle was submerged i n a fluorocarbon layer. A t such a low rate the oxygen gas emerged from the nozzle as individual bubbles rather than a continuous jet. The oxygen bubbles had an average diameter of about 0.4 cm for the nozzle size of 0.3 cm inner-diameter and an average diameter of about 0.10 cm for the nozzle size of 0.05 cm diameter. Provision was made to humidify the oxygen gas when necessary to equalize the partial pressures of water in the gas and i n the blood. The gas bubbles ascended through the fluorocarbon layer to the fluorocarbon-blood interface. As the bubbles ascended through this inter face, a film of fluorocarbon remained around the gas bubbles, forming the encapsulating liquid membrane. The encapsulated bubbles then rose through the blood phase where the oxygen inside the bubbles permeated out into the blood and carbon dioxide i n the blood permeated into the bubbles. Thus, the blood was changed from the state which was carbon dioxide-rich and oxygen-depleted to the state which was carbon dioxidelean and oxygen-replenished. The oxygen and carbon dioxide partial pressures in the blood were monitored by the two probes, or electrodes, suspended in the blood phase. The encapsulated bubbles eventually emerged from the blood phase forming a phase which was apparently gas i n a continuous fluorocarbon foam and moved down a slant glass tube of 1 cm i n diameter and 16 cm in length into a receiving separatory funnel. In this slant glass tube there was an opportunity for a blood-gas interface to occur; however, obvious modification in the apparatus could eliminate this interface. The liquid membrane encapsulated bubbles collapsed with time in the separatory funnel, forming four phases. The top was the spent gas from the oxygenator which had reduced oxygen content and increased carbon dioxiae content. Below this phase was the oxygen bubbles in a continuous fluorocarbon phase (oxygen i n fluoro carbon foam). This phase isolated a blood phase below it from the poten tially damaging gas phase. The third phase, oxygenated blood carried over by the oxygen i n fluorocarbon foam, was usually very small i n com parison with the quantity of blood oxygenated (about 1 % ). Since it was protected from directly contacting the spent gas, it should be recirculated to the patient. The fourth phase was the solution of fluorocarbon com pounds which were reused to form liquid membranes encapsulating new oxygen bubbles. In all the runs the fluorinated-compound solution and blood carried over were measured. Samples of blood were taken directly from the column from time to time during the examination run. Results and

Discussion

L i q u i d Membrane Formation. The most important test of liquidmembrane oxygenation was determining whether stable fluorocarbon-


6



Table I.

Transfer of Oxygen and Carbon Dioxide"

Time (Min.)

Οΐ Partial Pressure in Blood (mm Hg)

COi Partial Pressure in Blood (mm Hg)

Accumulated OiFlow (liters at 1 atm, 25°C)

0 2 5 10 12 14 17 22 37 43 47 58 70 76 85 125

17 18 19.2 21.0 24.5 27.0 30.5 32.4 39.0 44.0 49.5 62 76 84 99 350

17.2 17.2 17.2 17.2 16.4 16.4 16.4 15.0 15.0 15.0 15.0 15.0 15.0 15.0 15.0 15.0

0 0.08 —

0.31 0.38 0.46 0.59 0.63 0.88 1.10 1.3 1.84 2.4 2.65 3.10 5.58

Total amount of blood in foam coalescer after 125 min = 2 grams. Total amount of fluorocarbons in foam coalescer after 125 min = 15 grams. ° Run No. = 10, temperature: 25°C, blood: 190 grams fresh bovine blood, hemo globin content: 11.8 grams in 100 grams blood, fluorocarbon phase: 110 grams, oxygen nozzle size = 0.3 cm in diameter. type liquid membrane can be built on the surfaces of oxygen bubbles. Fluorocarbons or their derivatives were used for making the liquid membranes because recent work (6, 7, 8, 9, 10, I I ) has shown that several of this group of compounds cause minimal damage i n con tact with blood. The fluorocarbon solution was effective i n forming stable membranes around oxygen bubbles. The presence of stable encap sulating liquid membranes during the rise of the bubbles through the blood is supported b y the formation on top of the blood phase of a phase which seemed to be a foam of gas bubbles i n a clear liquid. W h e n this foam was removed from the top of the blood phase and allowed to col lapse, it was dominately liquid fluorocarbon (see Table I ) . W i t h the high density of the fluorocarbons (about 1.8 grams/cc) and the low gas flow rate (about 2 liters/hour), it is very unlikely that any substantial quantity of fluorocarbon thrown to or entrained to the top of the blood phase. The liquid membrane formation hypothesis was supported further when a substantial residence time was used for the gas i n fluorocarbon foam on the top of the blood phase i n the column. Under this condition some of the foam would collapse on top of the blood phase, resulting i n the formation of fluorocarbon droplets. These droplets could be observed


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7



to fall down through the column of blood counter to the rise of bubbles up through the column. This observed counter-flow of free fluorocarbon droplets down with continuous supply of fluorocarbon u p the column is strong evidence for the fluorocarbons being carried up the column with the bubbles as liquid membranes. Liquids (either solvents or solvents plus surfactants) other than fluorocarbons might be used to form liquid membranes for blood oxy genation. However, the following criteria must be satisfied: ( 1 ) High-surface activity at the liquid membrane-blood interface— so that a liquid membrane can form around each gas bubble (2) Insignificant solubility i n water and i n the much more complex fluid blood—so that objectionable quantities are not returned to the animal (3) Good compatibility with blood—so that blood w i l l not be sig nificantly damaged or poisoned by contacting the liquid membranes phase (4) H i g h oxygen absorption capacity—so that it can rapidly transfer the oxygen from the bubble to the blood (5) H i g h carbon dioxide permeability—so that the liquid mem brane i t forms allows rapid transfer of carbon dioxide from the blood phase to the bubbles. Oxygenation Rate. The progress of blood oxygenation i n the glass column was indicated not only by the increase of oxygen partial pressure in blood (Table I and Figures 2 and 3) but also by the change of blood

11 0

I 20

I 40

I 60

I 80

I 100

ι j* j* I 120 1 3 0 ^ ) 2 0

I 40

I 60

OXYGENATION TIME (MIN.)

Figure 2.

Blood oxygenation


I 80

8


color from dark red gradually to bright red when more and more oxygen molecules combined with hemoglobin as discussed before. The oxygenation rate was measured; the initial slope of the curve using liquid membranes i n Figure 2 is proportional to the rate of oxygen transfer. A t about 100 m m H g 0 partial pressure, there is a sharp change i n the slope of the curve. This corresponds to the partial pressure where the hemoglobin becomes saturated (15), and additional oxygen put into the blood must be dissolved largely i n the blood. A n additional mole of oxygen physically dissolved i n the blood raises the oxygen partial pressure much more than an initial mole of oxygen which could be bound by the hemoglobin. Thus, the change i n slope does not reflect a change i n oxygen transfer rate.


2

AVE. 0

AVE. 0

INLET

2

NOZZLE SIZE 600 |_

ο ο ο -

(M Ο

U

FL0WRATE

• 0.28 • 0.57

· 0.3 cm • 0.05 cm

500

2

( Liters/ml n.)

TEMP.:

25°C

(A) 14.8 gm HEMOGLOBIN IN 100 gm BLOOD (B) 12.1 gm HEMOGLOBIN IN 100 gm BLOOD

400

11. Ο

LU =

on

300

200

100

100

200

300


Figure 3.

Blood oxygenation

The rate of oxygen transfer per unit area of liquid membrane was estimated. The rate of oxygen uptake was measured from the initial slope of the curve for liquid membranes i n Figure 2 and the measured 13 gm/100 m l hemoglobin content of the blood. The volume formation


1.

L i AND ASHER

rate of liquid-membrane encapsulated bubbles was determined from the measured oxygen flow rate of 1.9 liters/hour. The encapsulated bub ble diameter was estimated at 0.4 cm, and the rise velocity of the encap sulated bubbles i n the blood was estimated at 0.15 ft/sec. The rough estimate of the rate of oxygen transport calculated from the above mea surements and estimates was over 100 cc 0 / m i n / m . This rate does not differ within the confidence limits of the assumptions from the 30 to 80 cc 0 / m i n / m measured i n earlier fluorocarbon blood oxygenators (6,7,8). This is consistent with the major resistance to oxygen transport occurring in the blood phase as was thought to be the case i n the earlier fluoro carbon oxygenator. The estimated rate of oxygen transport using liquid membranes is also consistent with the typical 40-60 cc of 0 / m i n / m measured i n polymeric membrane oxygenator using high transport mem branes where the major resistance to transport was thought to be i n the blood phase (17,18,19). 2

2


9


2

2

2

2

A n attempt was made to determine experimentally if the liquid membrane was contributing a major portion of the resistance to oxygen transport or if, as suggested above, the major resistance to transport was in the blood phase. The experimental apparatus that was used with the liquid membrane was used, except that no fluorocarbons were introduced to the bottom of the column and the bubbles were formed directly i n the blood. The rates of oxygen transport under 100 mm H g of 0 partial pressure were somewhat but not markedly higher without the liquid membrane, as shown in Figure 2. Figure 2 shows also that the times required to reach high oxygen partial pressure, with and without liquid membranes are substantially longer than with the developed oxy genators. This occurred because the very large bubbles (about 0.4 cm) used in the experiment expose a much smaller area of blood for oxy genation than the much smaller bubbles generated (on the order of 0.03 cm) i n the developed oxygenators. 2

The lower rate with the liquid membrane might indicate some oxygen transport resistance of the liquid membrane. However, other factors could also account for the different rates. Subsequent experiments were per formed using transparent plasma to allow visualization of the phenomena. In these experiments the oxygen bubbles formed from a nozzle submerged in the plasma were smaller than the liquid membrane-encapsulated bub bles formed at the plasma-fluorocarbon interface from a nozzle sub merged i n the fluorocarbon. The same phenomena of smaller bubbles being formed without the liquid membrane quite probably also occurred in the experiments with the opaque blood. The smaller bubbles without liquid membrane, which would provide more blood surface for oxygena tion, is consistent with observed slightly more rapid oxygenation rate. In any case the small difference in rates of blood oxygenation observed



10


with and without liquid membranes would indicate the relative resistance to oxygen transport of the liquid membrane is small. The diameter of the oxygen bubbles formed i n the fluorocarbon was reduced from 0.4 cm to 0.1 cm for some experiments. This would be ex pected superficially to increase the surface area for transport and the oxygen transport rate particularly since a higher oxygen rate was used. However, the rate actually decreased a bit (Figure 3 ) . Subsequent ex periments using transparent plasma cast some additional light on this phenomenon. W h e n small diameter nozzles were used i n the fluorocar bon phase, small bubbles were formed, which rose to the fluorocarbonplasma interface. The bubbles collected and coalesced on the fluoro carbon side of the interface until enough volume accumulated so that the buoyant forces exceeded the interfacial tensions, allowing the fluorocarbon-encapsulated bubble to rise into the plasma phase. Thus, smaller diameter nozzles i n the fluorocarbon phase d i d not produce smaller diam eter liquid membrane-encapsulated bubbles in the plasma phase. Using the small diameter nozzle at higher gas flow rates produced larger diam eter liquid membranes. The gas bubbles actually formed clusters at the interface due to lack of time for coalescence. These clusters were larger than the individual liquid membrane encapulated bubbles formed at lower gas rates. This may be due to reduced buoyancy resulting from the addi tional fluorocarbon around each small bubble i n the cluster. The above mentioned observations with plasma are consistent with the blood oxy genation results, specifically, the small diameter nozzle d i d not yield faster oxygenation and the higher oxygen flow rate produced a lower oxygena tion rate. It is desirable to use very small encapsulated bubbles for oxygena tion. If 50 μ encapsulated bubbles, occupying 20 volume-% of a blood containing vessel, would be used effectively, only a 250 m l vessel would be required to give 6 square meters of interfacial area for oxygen trans port. If based on the rate of oxygen transport per unit area previously measured at blood-fluorocarbon interfaces and rates estimated from this work, the 6 square meters would be adequate for the total rest oxygen requirements (of about 18 liters of oxygen per hour (16)) of a human. W h i l e it is unlikely that such a small oxygenator would be developed, the calculations indicate the potential for small volume. A method of generating and effectively using small diameter liquid membranesencapsulated oxygen bubbles is needed. Perhaps, the methods used to make small diameter liquid membranes for other applications (2, 3, 4) could be used. Carbon Dioxide Removal f r o m Blood. Carbon dioxide was removed from blood by the liquid membrane-coated bubbles. The decrease of C 0 partial pressure was from 26 m m H g to 21 m m H g in 12 m i n at an 2


1.

L i AND ASHER

11


oxygen flow rate 0.58 liters/min with the smaller diameter 0.05 c m nozzle. Similar results of C 0 removal are shown i n Table I at a dif ferent oxygen flow rate and bubble size. T h e C 0 partial pressure in the blood, as withdrawn from the animal, should have been higher than the 26 mm H g typically measured at the beginning of a run. T h e low C 0 partial pressure was believed to result from CO2 that escaped from the blood into the atmosphere resulting from the favorable C 0 partial pressure difference between the blood and the atmosphere when the blood was stored i n the refrigerator (20). 2

2

2


2

• LIQUID MEMBRANE (LM) RUN • BLANK RUN (NO LM) TEMPERATURE = 25°C AVE. 0 FL0WRATE = 0.28 Liters/min. 2

THE C 0 PARTIAL PRESSURE WAS ELEVATED

110

2

BEFORE INITIATING BOTH RUNS. 100

Ε Ε Ο Ο Ο

Ο Ο

OU

50

CO to LU OU û_

·(?)

40 30 20 10 20

40

_L_ 60

80

100 120 140 160 180 200


Figure 4.

Removal of carbon dioxide from blood

T o eliminate the possibility of a measurement artifact at low con centrations, the C 0 partial pressure of some blood was increased to 100 m m H g b y bubbling C 0 through the blood. The transfer of C 0 from this blood is shown i n Figure 4. Here the C 0 partial pressure dropped from 85 mm H g to 51 m m H g i n 154 min, using oxygen bub bles without liquid membranes (formed directly i n the blood), and 2

2

2

2


12


from 100 m m H g to 41 mm H g i n 176 min, using liquid membraneencapsulated oxygen bubbles. This confirms C 0 transport from the blood through the liquid membrane to the gas. Also, it is consistent with the above mentioned carbon dioxide removal through liquid membranes measured at lower partial pressure. The small, if not negligible, difference in rate of C 0 removal with and without liquid membranes, shown by the parallel lines through the data i n Figure 4, indicate that the resistance to C 0 transport of the fluorocarbon liquid membranes is quite low. 2

2

2

The apparatus used for this study produced low transport rates for C 0 , as well as the previously discussed 0 , with and without liquid membranes compared with developed oxygenators. The reason for this slow transport is the very large (approximately 0.4 cm) liquid membrane encapsulated bubbles contrasted with the small bubbles of developed oxygenator. A means is needed to produce small fluorocarbon liquid membranes i n blood so that the rapid transport achieved i n other liquid membrane applications using small diameter liquid membranes can be achieved for transferring gases to and from blood.


2

2

L i q u i d Membrane Stability. W h i l e studies of other investigators have indicated that the blood has good œmpatibility with the liquid fluorocarbon surface, they also indicate that fluorocarbon droplets should not be introduced to the bloodstream of animals (6, 7, 8 ) . L i q u i d mem brane rupture i n the oxygenator apparatus could produce droplets from the fluorocarbon which had formed the liquid membrane. These droplets would be entrained and returned to a test animal with the oxygenated blood. As a preliminary test for liquid membrane rupture and droplet formulation, the oxygen flow into apparatus was momentarily stopped, and blood samples were withdrawn for examination. The blood samples were centrifuged at 20,000 r p m at a distance of 4.5 inches for 20 minutes i n a centrifuge maintained at 20°C. After centrifugation the blood separated into two layers, a top layer of plasma and a bottom layer of red cells. Since the liquid fluorocarbon is immis cible with the blood and is much heavier than the blood, entrainment of fluorocarbon in blood should result in the formation of a small, third layer of the fluorocarbon at the very tip of the pointed centrifuge tubes after such intensive centrifugation. However, no such layer was found in the tubes for all the four blood samples tested. The blood samples were also examined carefully under microscope. N o tiny droplets of fluorocarbon were noticed. W h i l e it is possible that a few liquid membranes ruptured and escaped detection and more definitive testing would be required before application, instability of the liquid membranes does not seem to be a major problem.


1.

L i AND ASHER


13


Conclusions L i q u i d membrane of fluorocarbons can be formed encapsulating oxygen bubbles i n blood. The transfer of oxygen and carbon dioxide through the liquid membrane to and from the blood, respectively, have been shown. Very similar transfer rates with and without liquid mem branes indicate that the resistance of the liquid membranes is small. The specific rate of oxygen transfer per unit of liquid membrane area seems to be quite reasonable. However, methods to form and utilize effectively much smaller diameter liquid membranes, perhaps similar to those used i n other liquid membrane applications, would be required to obtain enough membrane area per unit blood volume for a practical blood oxygenator. The stability of the liquid membranes does not seem to be a major problem; however, more definitive liquid membrane sta bility information would be required before the blood oxygenator application. Such a liquid membrane oxygenator would present a liquid fluoro carbon interface to the blood. Studies of earlier investigations have indicated good, and perhaps even unique, blood compatibility with these liquid fluorocarbon interfaces; however, more information is needed. In the liquid membrane blood oxygenator new blood-fluorocarbon inter faces are generated constantly as new liquid membranes are formed. The interfaces are collapsed returning materials held at the interface to the blood as the bubbles are collapsed. Additional blood compatibility study is needed i n systems where the blood-fluorocarbon interface is generated continuously and then collapsed i n long testing periods. For such infor mation to be truly convincing, the experiments would have to be per formed in vivo. Presuming the successful investigations i n the above mentioned critical areas, a liquid membrane blood oxygenator might be developed. Such an oxygenator would be unique and offer many potential advan tages, including the possibility of long term oxygenation. Acknowledgment The authors would like to thank H . W . Wallace of the University of Pennsylvania, R. Ferguson of the National Heart and L u n g Institute, and C . G . Young, R. P. Cahn, and A . L . Shrier of Esso Research and Engi neering C o . for their helpful discussions. Also, the authors thank T. H u c a l for his assistance with the experimental work. Literature

Cited

1. Chem. Eng. News (Oct. 5, 1970), 36; (June 7, 1971) 30. 2. Li, Ν. N., A.I.Ch.E. J. (1971) 17, 459.



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3. L i , Ν. N., Ind. Eng. Chem., Process Res. Develop. (1971) 10, 215. 4. L i , N . N., Shrier, A. L., "Recent Developments in Separation Science," Vol. 1, p. 163, Chemical Rubber Co., Cleveland, 1972. 5. L i , N . N., Asher, W. J., U.S. Patent pending. 6. de Filippi, R. P., Nose, Y., et al., Proc. Artif. Heart Program Conf., p. 381, June 9-13, 1969. 7. Anderson, R. M., Nose, Y., et al., "Development of a Liquid-Liquid Blood Oxygenator," Annual Report, PH 43-68-1393 (July 24, 1969). 8. Anderson, R. M., Nose, Y., et al., Trans. Amer. Soc. Artif. Intern. Organs (1970) 16, 375. 9. Pitzele, S., et al., Surgery (1970) 68 (6), 109. 10. Chem. Week (January 13, 1971), 42. 11. Sloviter, Η. Α., Petkovic, M . , Ogoshi, S., Yamada, H . , J. Appl. Physiol. (1969) 27, 666. 12. Geyer, R. P., Monroe, R. G., Taylor, K., "Organic Perfusion and Preserva tion," J. C. Norman, Ed., p. 85, Appleton Century-Crafts, 1968. 13. Technical Bulletin, 3M Mfg. Corporation. 14. Technical Bulletin, Dupont Chemical Corporation. 15. Langley, L . L., "Physiology," 2nd ed., McGraw-Hill, New York, 1965. 16. Keller, Κ. H . , Leonard, E. F., "Engineering Analysis of the Functions of Blood," American Institute of Chemical Engineers, New York, 1968. 17. Peirce, E. C., II, Mathewson, W. F., Jr., "Design and Fabrication of Blood Oxygenator for Circulatory Assist Devices," Artif. Heart Prog. Conf. Proc.,p. 450-416 (June 9-13, 1969). 18. Landé, A. J., Tiedeman, R. N., Subramanian, V. Α., Fillmore, S. J., Lillehei, C. W., "Progress in the Testing and Development of Practical Flat Plate Membrane Oxygenators for Cardiopulmonary Assist," Artif. Heart Prog. Conf. Proc.,p. 417-430 (June 9-13, 1969). 19. Peirce, E. C., II, "A Comparison of the Landé-Edwards, the Peirce, and the General Electric-Peirce Membrane Lungs," Trans. Amer. Soc. Artif. Intern. Organs (1970) 16, 358-364. 20. Levinson, S. Α., MacFate, R. P., "Clinical Laboratory Diagnosis," Chap. 9, Lea and Febiger, Philadelphia, 1969. RECEIVED

November 22, 1971.


Blood Oxygenation by Liquid Membrane Permeation - Advances in

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